Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Blood and Lymphatic Diseases Chapter 28 Nester 4th. Ed. Topic Overview Anatomy & Physiology Bacterial Diseases of the Blood Vascular System Endocarditis Subacute Bacterial Endocarditis Acute Bacterial Endocarditis Septicemia Gram Negative (-) Septicemia Topic Overview Bacterial Diseases of the Lymph Nodes & Spleen Zoonoses Tularemia Brucellosis Plague Topic Overview Viral Diseases of Lymphoid & Blood Vascular Systems Infectious Mononucleosis (Mono) Yellow Fever Dengue Fever Protozoan Diseases Malaria The Blood Vascular System Normal flora There are NONE. Diseases Systemic Can produce disease in vital organs Can cause circulatory system itself to stop functioning Can be rapidly fatal Lymphatic System Lymphatic vessels Readily permeable Take up foreign material Invading microbes Microbial toxins Other antigens Lymphatic System Lymph Nodes Act to trap foreign material Contain phagocytic cells & antibody producing cells Lymphangitis Demonstrates ability of lymph nodes to clear an infection (even if only temporarily) Bacterial Diseases of the Blood Vascular System Bacterial Endocarditis What is it? Infection of heart valves or endocardium usually localized to one of the heart valves on the left side Acute Starts abruptly (sudden and severe onset) Virulent infection of the heart Starts with abrupt fever ABE Pathogenesis Usually an infection is seen somewhere else or IV drug abuse is evident Virulent bacteria Invasion of heart and both normal & abnormal valves Rapid progression leading to permanent damage or heart failure ABE Organisms Staphylococcus aureus Streptococcus pneumoniae Neisseria gonorrhoeae other bacteremia producing bacteria Sub-acute Bacterial Endocarditis What is it? Infection of the endocardium Usually localized to one of the heart valves on the left side Caused by less virulent organisms More protracted course Commonly occurs in abnormal heart valves most often resulting from birth defect rheumatic fever other diseases Sub-acute Bacterial Endocarditis (SBE) Causative Agent(s) Usually normal flora of the mouth and skin viridans Streptococci Staphylococcus epidermidis General Symptoms marked fatigue slight fever become ill and lose energy gradually over weeks to months SBE Pathogenesis organism gets into blood dental procedures tooth brushing other trauma abnormal valve forms a thin clot on it clot traps organisms forming a biofilm Protects organism from phagocytes and antibiotic treatment SBE Pathogenesis Antibiotics can make the bacteria clump together & adhere to the clot more clot forms cycle - growth, clot, growth, clot, etc. builds up a mass called a vegetation bacteria continually wash off pieces of the mass may come off too Weakens the vessel – can lead to an aneurysm Circulating immune complexes can lodge in eyes, skin, organs, etc. causing damage SBE Pathogenesis can burrow into the heart valve abscesses damaged valve leaks Diagnosis venous blood from two anatomical locations culture on blood agar SBE Epidemiology cases with viridans Streptococci decreasing antibiotics for people with valve problems before dental work cases with Staphylococcus epidermidis IV drug abusers hospitalized people with plastic IV catheters in place for a long time people with artificial heart valves SBE Prevention no proven method antibiotics before bacteremia causing procedures aseptically inserting catheters moving IV catheters every few days take out catheters ASAP SBE Treatment with bactericidal agent Usually two or more together for prolonged period Penicillin & gentamicin 1 or more months Septicemia Systemic infection (blood poisoning) Acute disease ~400,000 cases / year in U.S. Caused by Gram (-) bacteria (30% of all cases) Gram (+) bacteria viruses fungi Septicemia Symptoms violent shaking chills fever anxiety rapid breathing as septic shock develops urine output decreases respirations & pulse increase vasoconstriction occurs Gram (-) Septicemia Pathogenesis uncontrolled infection somewhere due to some alteration in body defenses alternation in normal immune response (surgery, trauma, subluxations) may allow infection to occur endotoxin released from outer cell wall from organism in blood or at local site of infection antibiotics that effect the cell wall enhance the release of endotoxin Gram (-) Septicemia Pathogenesis macrophages and circulating leukocytes respond defensively to endotoxin Intense response good response if the infection is localized bad if the endotoxin enters circulation Gram (-) Septicemia Pathogenesis endotoxin causes triggering of macrophages throughout body resulting in a systemic reaction intense immune response Hypersensitivity Cascade of harmful events (fig. 28.3 p. 720) Macrophages important in defenses but play a key role in septic shock Gram (-) Septicemia Pathogenesis Interaction of endotoxin with macrophages cause the cell to produce & release cytokines tumor necrosis factor – TNF induces fever induces inflammation (PMNs -polymorphonuclear neutrophils) Gram (-) Septicemia interleukin-1 acts with TNF to cause fever & release of leukocytes from bone marrow causes release of enzymes from polymorphonuclear leukocytes complement attracts leukocytes and causes them to release tissue damaging lysosomal enzymes causes capillaries to leak plasma Gram (-) Septicemia Pathogenesis endotoxin induces clotting disseminated intravascular coagulation (DIC) uses up clotting factor leads to hemorrhaging cytokines decrease muscle tone of heart and vessels hypotension shock - not enough oxygen in vital organs Gram (-) Septicemia Pathogenesis Lung - most susceptible to permanent damage from endotoxemia can lead to death even infection is cured and shock is reversed Gram (-) Septicemia Epidemiology Mainly a nosocomial infection General trend of increasing incidence increased life span antibiotic suppression of normal flora immuno-suppression drugs equipment susceptible to biofilm formation Prevention Prompt ID and treatment of localized infections Gram (-) Septicemia Treatment appropriate anti-microbial agent measures to control shock immunotherapy death rate is still 30-50% monoclonal antibody directed against endotoxin or TNF Some benefit if given early before shock develops Studies looking at recombinant technology protein (Drotrecogin alpha) Acts to oppose effects of cytokines Bacterial Diseases of Lymph Nodes and Spleen Characterized by enlarged lymph nodes and spleen Three examples All three are zoonoses All three are uncommon in human disease in U.S. Seen a threat due to presence in animal population Tularemia (Rabbit’s Fever) incubation period - (usually 2-5 days) following bite of tick or insect or handling wild animal Usual symptoms skin - steep-walled ulcer enlarged regional lymph nodes fever, chills and achiness Unusual symptoms eye - conjunctivitis lung - pneumonia two routes of entry GI tract - vomiting, diarrhea Usually clears in 1-4 weeks, sometimes months Tularemia Causative agent Francisella tularensis pleomorphic, non-motile, Gram (-) rod needs cysteine to grow Tularemia is widespread in animals in the U.S. rabbits, muskrats, bobcats “Rabbit Fever” Tularemia Pathogenesis - skin example organism enters skin lymph vessels carry the organism to the lymph nodes lymph nodes enlarge (lymphangitis) fill with pus drain organism spreads via lymphatics and blood vessels Tularemia Pathogenesis – pneumonia Occurs in 10-15% of cases Enters lungs from bloodstream or inhalation High mortality – 30% Most pneumonias occur among lab workers Tularemia Pathogenesis organism ingested by phagocytic cells and grows Why it can persist fro months despite high Antibody levels cell-mediated immunity cures 90% survive without treatment Tularemia Epidemiology portals of entry unnoticed scratches mucous membranes oral cavity via food lung by inhalation Tularemia Epidemiology 150-250 cases per year Eastern U.S. winter from skinning rabbits (rabbit fever), squirrels, muskrats, beavers Western U.S. summer tick and deer fly bites Tularemia Prevention standard practices to prevent vector borne diseases gloves, goggles, face masks for people skinning animals vaccine for lab workers and those of high risk of infection Treatment tetracycline gentamicin Brucellosis “Undulant Fever” or “Bang’s Disease” Organism Brucella melitensis abortus - cattle melitensis - goats canis - dogs suis - pigs strict aerobe, nonmotile, pleomorphic, small Gram (-) rods Brucellosis Symptoms Usually gradual and vague Mild fever Sweating Weakness Aches & pains Enlarged lymph nodes Weight loss Recurrence possible over few weeks to months Brucellosis Pathogenesis organism enters breaks in skin organism penetrates mucous membranes disseminated by lymphatic and blood vessels organism grows inside phagocytes infection persists for months mortality - endocarditis - 2% frequent serious complication - osteomyelitis Brucellosis Epidemiology ~150 cases / year in U.S. 10-20 times that number go unreported usually a chronic infection of domestic animals 60% of cases mammary glands - contaminate milk uterus - abortions but not in humans meat packing industry less than 10% of cases contaminated milk or unpasteurized milk products Brucellosis Worldwide – major problem causing yearly losses in millions of dollars In U.S. infections have been acquired from elk, moose, bison, caribou & reindeer ~20% of Yellowstone bison population is infected Prevention pasteurization inspection of animals goggles, gloves live attenuated vaccine for domestic animals Brucellosis Treatment Most cases resolve within 2 months w/o treatment ~15% symptomatic more than 3 months If needed tetracycline with rifampin ~ 6 weeks may use streptomycin or gentamicin with rifampin Plague “Black Death” Killed 1/4 of Europeans between 1346 & 1350 Crowding and large rat population played major role Basis for “Ring around the Rosie” “Would not touch them with a 10 foot pole” Potential bioterrorism disease Plague Symptoms develop abruptly 1-6 days after bite by infected flea Bubonic plague enlarged and tender lymph nodes – buboes high fever, shock, delirium, patchy bleeding under skin Pneumonic plague Cough and bloody sputum Plague Organism - Yersinia pestis facultatively, intracellular enterobacterium small, oval, pleomorphic, non-motile, Gram (-) rod grows best at 25 degrees Celsius bipolar staining - safety pin Plague three distinguishable plasmids Smallest codes for protease “Pla” Causes blood clots to dissolve by activating plasminogen activator Destroys C3b and C5a components of complement Mid-sized plasmid codes for (1) proteins that interfere with phagoyctes (2) regulators of proteins’ expression Proteins called Yops (Yersinia outer membrane proteins) Bacteria loses virulence if this plasmid is lost Plague Plasmids Largest plasmid codes for antigen F1 This protein becomes part of an antiphagocytic capsule and is important component of plague vaccine Virulence factors - Table 28.4, p. 724 Plague Pathogenesis fleas bite infected human or rat flea body temp is 25 degrees Celsius organism grows well and blocks flea’s GI tract hungry flea bites human many times and regurgitates chronically infected fleas excrete organism Plague Pathogenesis Protease Pla is essential for spread of organisms to lymph nodes Organism taken up by macrophages and are not killed Macrophages die & release bacteria (now encapsulated) multiply & release F1 capsular material Fra 1 - gene for non-phagocytic capsule After several days – acute inflammation & tenderness of lymph nodes – bubonic plague Lymph nodes necrose – spread to bloodstream – Septicemic plague Endotoxin release results in shock and DIC Plague Pathogenesis organism can get to lungs 10-20% of the time resulting in pneumonic plague organism passed person to person via respiratory droplets is extremely dangerous - organism is easily transmitted mortality - untreated bubonic - 50-80% pneumonic -100% within a few days Plague Epidemiology Endemic in all continents except Australia In U.S. mostly confined to wild rodents in ~15 western states Disease in prairie dogs, rock squirrels, and their fleas - reservoirs Rats, rabbits, dogs, and cats - maybe Hundreds of species of fleas carry plague ~15 CASES / YEAR Plague Prevention rat control Insecticides rope guards on moored ships killed vaccine available short term immunity to control epidemics high risk people - labs and endemic areas Plague Treatment Tetracycline used prophylactically for exposures Alone or with gentamicin effective if given early in disease Can be used to control epidemics Viral, Protozoan and Multi-Cellular Diseases Infectious Mononucleosis “Mono”, “kissing disease” Symptoms Usually appear after incubation period of 3060 days Fever Sore throat (pus covered) Marked fatigue Enlargement of spleen and lymph nodes Most cases fever & sore throat gone in ~2 weeks Enlarged lymph nodes in 3 Infectious Mononucleosis Causative Agent Epstein-Barr virus (now called Human herpes virus type 4) Linear ds DNA virus – Herpesviridae family enveloped Unknown until the 1960s Originally isolated originally from a patient with Burkitt’s lymphoma Infectious Mononucleosis Pathogenesis Primary disease – throat infection Replication in epithelium of mouth, glands & throat Virus carried to lymph nodes via lymphatics Infects B lymphocytes (up to 20% are infected during illness) Infection can be productive Virus replicates in cell & kills B cell Infection can be non-productive Virus establishes a latent infection existing either as extrachromosome circular DNA or integrated into the host cell chromosome at random sites Infectious Mono Latent infection occurs in other B-cells B-cells differentiate Make IgM heterophile Ab Antibody against antigens of another animal sheep, horse, ox) Used for diagnosis No pathologic significance Does not react with Epstein-Barr virus Latently infected B-cells are immortal Infectious Mononucleosis Activation of T-lymphocytes occurs T-cells kill infected productive cells T-cells appear abnormal - diagnostic for “mono” Occasionally misdiagnosed as leukemia Enlargement of spleen and lymph nodes reflects active replication of lymphocytes. In rare cases where death occurs Splenic rupture Most likely within 3-4 weeks of onset of illness Infectious Mononucleosis Epidemiology worldwide saliva transmission - “kissing” most people of middle age have Ab virus in saliva of 20% of the people previously infected- carriers Infectious Mononucleosis Epidemiology economically disadvantaged parts of the world even in the U.S. - especially urban areas infection occurs earlier in life no significant illness 90% are infected by 6 years of age Infectious Mononucleosis Epidemiology more affluent societies infections occurs later in life adolescents, teenagers, young adults 15-24 yoa half those infected actually get “mono” no disease in the other half Infectious Mono Epidemiology Virus present in salvia up to 18 months following infection Can occur intermittently for life No animal reservoir Infectious Mononucleosis Prevention don’t share objects contaminated with saliva soda cans, tooth brushes, drinking glasses, etc. Treatment Acyclovir Inhibits productive infection by virus No activity against latent infection For serious cases only Those with liver and spleen enlargement Those with prolonged disease Chronic EBV Infection Chronic EBV infection severe disease after the primary disease pneumonitis hepatitis hematological abnormalities prolonged relapsing course sometimes death not associated with chronic fatigue syndrome Epstein-Barr Virus Burkitt’s lymphoma children in east Africa and New Guinea viral DNA is found in > 90% of the tumors malaria may be a cofactor increases chances of tumor formation EBV found in only 20% of Burkitt’s lymphoma that occurs in other parts of the world Epstein-Barr Virus Nasopharyngeal carcinoma males of Chinese origin (southeast Asia) viral DNA is found in > 90% of the tumors EBV in immunodeficient hosts lymphoproliferative diseases not the Burkitt’s type Yellow Fever First recognized in 1648 Flaviviridae Arbovirus Yellow fever virus Epidemic in Yucatan, Mexico ss RNA genome Vector Aedes aegypti mosquito Yellow Fever Mild disease Fever Headache Very severe disease High fever Nausea Bleeding from nose and mouth G.I. Bleeding - “black vomit” jaundice - hence name Mortality - 50% Yellow Fever Pathogenesis mosquito with virus bites human virus gets to blood and lymphatic vessels viremia liver - jaundice small blood vessels - petechiae throughout body heart - direct damage to heart muscle blood vessel injury - DIC Yellow Fever Epidemiology Reservoir - mosquitoes and primates Recognized in 1648 (Yucatan, Mexico) Central and South America 1989 Bolivian epidemic in poor people who moved to the jungle to grow coca Africa Imported from Africa 1960’s Ethiopian epidemic of 100,000 30,000 dead Any of the tropical jungles No U.S. outbreaks since 1905 Yellow Fever Epidemiology Control Urban areas - insecticides sprayed in breeding areas Jungles - almost impossible Live attenuated vaccine highly effective for traveler’s to endemic areas No proven antiviral treatment Yellow Fever Prevention Insect repellent Protective clothing Mosquito netting Vaccine - Know Before You Go Certain countries require vaccine Live virus vaccine, single dose, confers immunity for 10 years or more Information found at the CDC website Dengue Virus Cause Flavivirus genus (related to yellow fever virus) Transmitted by Aedes aegypti mosquitoes Composed of single-stranded RNA Has 4 distinct serotypes (DEN-1, 2, 3, 4) Each serotype provides specific lifetime immunity, no cross over immunity All serotypes can cause severe and fatal disease Genetic variation within each serotypes Some genetic variants - more virulent Incubation – 2 – 15 days Dengue Fever (DF) & Dengue Hemorrhagic Fever (DHF) Clinical Characteristics (can include) Fever Headache Muscle and joint pain Nausea/vomiting Rash Hemorrhagic manifestations Skin hemorrhages: petechiae, purpura, ecchymoses Gingival bleeding Nasal bleeding Gastro-intestinal bleeding: hematemesis, melena, hematochezia Hematuria Increased menstrual flow Dengue Fever & Dengue Hemorrhagic Fever Incidence Variable, depending on epidemic activity Globally ~50-100 million cases of DF Several hundred thousand cases of DHF Fatality rate of DHF ~5% Americas 1995 – 250,000 cases DF 7,000 cases of DHF ~100-200 cases in U.S. each year (by travelers) Dengue Fever & Dengue Hemorrhagic Fever Costs ~ $250 million estimate in Puerto Rico in past 10 years Risk Groups Residents or visitors to tropical urban areas Children under 15 yoa No cross-immunity from each serotype Malaria Protozoan Sporozoan Plasmodium vivax - most U.S. cases falciparum - 30% of cases in U.S. malariae ovale Malaria Plasmodium species differ in: microscopic appearance life cycle type of disease severity treatment Malaria Anopheles mosquito - vector bites human and picks up gametocytes Life cycle parasites (sporozoites) enter RBC’s sporozoites develop and multiply in RBC’s RBC’s burst releasing merozoites merozoites infect more RBC’s - cycle some merozoites become male and female gametocytes - don’t contribute to symptoms Malaria Life cycle (Fig. 28.11, pg. 732) gametocytes enter mosquito intestine there they fuse to form a zygote and then a cyst the cyst ruptures releasing sporozoites sporozoites travel to the mosquito salivary gland mosquito bites a human sporozoites in saliva enter blood Malaria Life cycle sporozoites travel to the liver and multiply there (called hypnozoites in the liver) P. vivax and P. ovale hypnozoits responsible for relapse leave the liver and return to the blood (now called merozoites) merozoites enter RBC’s - back to first step of cycle Malaria Symptoms and pathogenesis recurrent bouts of fever followed by feeling healthy tied to cycle of RBC’s bursting releasing merozoites infections of RBC’s become synchronized each batch of infected RBC’s ruptures at the same time Malaria Symptoms and pathogenesis time frame until RBC’s burst malariae - 72 hours - fever every 4th day other species - 48 hours - fever every 3rd day RBC susceptibility to merozoites falciparum infects all red cells more severe disease other species infect only young and old cells less severe disease Malaria Consequences RBC’s become rigid clog capillaries decrease oxygen to organs cerebral malaria = stroke malaria of heart = failure spleen enlarges trying to filter out the parasites anemia due to bursting of RBC’s Immune system over stimulated by large amount of Ag - gets overworked Malaria Epidemiology Malaria may be a cofactor for Burkitt’s lymphoma tropical climates mostly 300,000,000 infected worldwide 1,000,000 deaths per year 20-30% of deaths of African children are due to malaria Malaria Epidemiology in the U.S. recognized in 1648 imported from Africa eliminated from the continental U.S. in the 1940’s now it’s back CA - organism found in mosquitoes FL - natural infection in a person bitten in FL Malaria Treatment different treatments are needed for different stages of the life cycle chloroquine for the RBC stages primaquine for the exoerythrocyte stages mefloquine or doxycycline for chloroquine resistant falciparum and vivax I.V. quinine, quinidine, sulfa drugs, tetracycline Malaria Prevention and control vaccine being developed increase access to treatment earlier diagnosis faster treatment travelers chloroquine weekly stops symptoms not infection primaquine needed to stop infection Conclusion What organisms cause the following diseases: Bacterial Diseases Sub-acute bacterial endocarditis Gram-negative septicemia Tularemia Bruscellosis Plague Viral Diseases Infectious Mononucleosis Yellow Fever Dengue Protozoan Diseases Malaria Conclusion What are the symptoms of the following diseases: Bacterial Diseases Sub-acute bacterial endocarditis Gram-negative septicemia Tularemia Bruscellosis Plague Viral Diseases Infectious Mononucleosis Yellow Fever Dengue Protozoan Diseases Malaria Conclusion What is the epidemiology and pathogenesis of the following diseases: Bacterial Diseases Sub-acute bacterial endocarditis Gram-negative septicemia Tularemia Bruscellosis Plague Viral Diseases Infectious Mononucleosis Yellow Fever Dengue Protozoan Diseases Malaria Conclusion What is the prevention and treatment of the following diseases: Bacterial Diseases Sub-acute bacterial endocarditis Gram-negative septicemia Tularemia Bruscellosis Plague Viral Diseases Protozoan Diseases Infectious Mononucleosis Yellow Fever Dengue Malaria Multi-cellular Parasitic Diseases Schistosomiasis