1. Blood
   • Liquid plasma
   • Formed cells
2. Heart pumps blood through arteries to all parts of the body
3. Veins return blood to the heart from all parts of the body
   • Valves keep blood moving in one direction
4. Capillaries join veins to arteries
   • Capillaries are permeable
5. Lymph
   • Lymph capillaries around tissue cells absorb interstitial fluid
     • This is filtered plasma that has moved from the blood capillaries into the spaces between the tissue cells
     • This fluid is the "lymph"
6. Lymph capillaries become larger lymph vessels called lymphatics
   • Lymphatics, like veins, contain valves that keep fluid moving toward heart
   • Lymph move from lymphatics through lymph nodes
     • Fixed macrophages and T and B cells are here
   • All lymph is dumped back into blood at juncture of vena cava and thoracic duct

• Uncontrolled proliferation of microbes within the blood
  • Sepsis is the condition of having septicemia
  • Gram negative rods are most often associated with sepsis
    • Entry points include catheters, intravenous feeding tubes, and focal infections
    • GNR’s endotoxins cause septic shock (Gram negative sepsis)
      • Recall: phagocyte ingests GNR; endotoxin is released; this stimulates phagocyte to release TNF; TNF causes capillaries to increase permeability; loss of fluids leads to shock
  • Gram positive organisms may lead to sepsis
    • Often introduced as a result of invasive procedures
• Symptoms include chills, fever, and lymphangitis
  • Inflamed lymph vessels visible as red streaks under the skin

1. Nosocomial situations
2. Focal infections
3. Small cuts and breaks in skin that go unnoticed
4. The bite of animal or infective insect vectors
5. Inhalation or ingestion and subsequent dissemination of microbe
6. Complications of ongoing, pre-existing disease

Reservoirs:

1. Zoonotic
   • Includes arthropodborne diseases
2. Environment
   • Includes soilborne diseases where organisms enter body through a cut, wound, or abrasion, or by inhalation

1. Soilborne
   • Anthrax (Bacillus anthracis)
   • Tetanus (Clostridium tetani)
   • Gas gangrene (Clostridium perfringens)
2. Zoonotic
   1. Non-arthropod-borne
      • Leptospirosis (Leptospira interrogans from dogs, cats, rats, mice, barnyard animals and environmental contamination by these animals)
      • Melioidosis (Pseudomonas pseudomallei from horses, rodents, dogs, cats, and environmental contamination by these animals)
      • Pasteurellosis (Pasteurella multocida, from bite of dog or cat; see page 314)
      • Cat-scratch disease (Bartonella henselae; page 314)
      • Brucellosis (see page 253)
   2. Arthropod-borne
      • Bubonic plague (Yersinia pestis, transmitted by the rat flea; PNEUMONIC plague is transmitted by human to human respiratory droplet contact)
      • Tularemia (Francisella tularensis, transmitted by ticks; also transmitted through contact with infected rabbits)
      • Lyme disease (Borrelia burgdorferi, transmitted by ticks)
      • Relapsing fever (Borrelia recurrentis, transmitted by ticks and lice)
      • Rocky Mountain Spotted Fever (Rickettsia rickettsii, transmitted by ticks)
      • Epidemic typhus, AKA Typhus fever (Rickettsia prowazekii, transmitted by head and blody lice)
      • Endemic typhus, AKA Murine typhus or Mexican typhus (Rickettsia typhi, transmitted by fleas)
      • Ehrlichiosis (rickettsia Ehrlichia chaffeensis, transmitted by ticks)
   3. Arthropod-borne viruses, AKA as Arboviruses (page 400)
      • Yellow fever, transmitted by Aedes aegypti mosquito
      • Dengue fever, transmitted by Aedes aegypti mosquito
3. Viral fevers (page 415)
   1. Lassa fever
   2. Marburg disease
   3. Ebola hemorrhagic fever
4. Nosocomial (pages 321-323)
   • Puerperal sepsis, AKA childbed fever (Streptococcus pyogenes, if uterine tissue is infected during birth process)
   • Various Gram negative pneumonias and UTIs ( E. coli, S. marcescens, E. aerogenes, E. cloacae, K. pneumoniae, Proteus species)
   • Staphylococcus auerus

Anthrax

• Bacillus anthracis
  • Gram positive, aerobic, endospore-forming rod
  • Usually a disease of grazing animals (zoonosis)
• People at risk include animal and animal product handlers (especially goat hair/animal hides from Middle East)
• Endospore enters through skin abrasion, ingestion, or can be inhaled
  • Cutaneous/intestinal/inhalation anthrax all can lead to septicemia (see p. 66 in lab notebook)
• Penicillin is drug of choice, but it is impotent against exotoxins

• Gangrene is the "death of soft tissue resulting from the loss of blood supply"
  • Ischemia is the "loss of blood supply"
  • Ischemia causes necrosis, death of the tissue
  • Ischemia results any time that blood supply is interrupted and is a complication of conditions such as diabetes and may also occur with wounds, especially muscular tissue wounds
• Clostridium species, Gram positive, endospore-forming anaerobic rods, grow very well under such anaerobic conditions
  • C. perfringens most commonly associated
  • As it consumes substances released from dying and dead tissue, it grows, fermenting carbohydrates and producing gases that cause tissue to swell
  • It releases exotoxins that kill cells, producing additional necrotic tissue
  • Eventually, all this enters the circulation
• Treatment is amputation and hyperbaric treatment

• Zoonosis that can lead to septicemia in humans
• Local infection with swelling and pain at wound site; may develop into pneumonia and septicemia
• Dog bites also transmit Clostridium species and other anaerobes such as Bacteroides and Fusobacterium
• By the way, human bites are pretty serious too

• Caused by Bartonella henselae, which is found in cats’ saliva
• Initial sign is a papule at infection site, followed by swollen lymph nodes, malaise, fever

• AKA undulant fever ("wavelike" fever)
• Zoonosis caused by three Brucella species, a Gram negative aerobic rod:
  • B. abortus: reservoir in elk/bison
  • B. suis: reservoir in swine
  • B. melitensis: reservoir in goats, sheep, camels and common outside of US; most virulent species
• Organism is transmitted by unpasteurized milk of cattle/goats and from contact with diseased animal tissue
  • Enters through GI tract or skin/mucous membrane abrasions
  • Once in body, multiplies in macrophages

• Yersinia pestis is etiologic agent
  • Gram negative rod
  • Survives and multiplies inside phagocytic cells
• Causes enlargement of lymph nodes (buboes)
• Septicemic plague can develop into pneumonic plague, which is almost 100% fatal
  • Pneumonic plague is spread by airborne transmission
• Reservoir is wild rodents, such as rats
  • Transmitted from one rat to another by the rat flea
  • If rat dies, flea looks for another host, either rat or human
  • Flea is not essential to transmission, as contact with infected animal can transmit disease

1. Relapsing Fever
2. Lyme Disease
3. Erlichiosis
4. Typhus
5. Tularemia

1. Starts as pinhead size larva that feeds on mice, where bacteria is first picked up
2. Feeds and molts 3 times
3. Once it reaches nymphal stage, it feeds on larger animals, such as deer and you, where it molts to adult stage

• Borrelia burgdorferi
  • Spirochete responsible for most common tickborne disease in US
  • All other species of Borrelia cause "relapsing fevers"
    • These must be directly observed in blood smear for diagnosis
    • They evade immunity by changing their antigens, each time causing a recurrence of fever
    • Like B. burgdorferi, these are also tickborne
• Reservoir is field mice
  • They maintain the spirochete in the tick population
  • Ticks feed and mate on deer
• First symptom is a bulls-eye type rash at bite site
  • Followed by flu-like symptoms
  • Heart becomes affected and neurological symptoms occur
  • Long-term symptoms resemble that of syphilis
• Diagnosis depends on suspicion of Lyme disease and ELISA screen for antibodies

• Ehrlichia bacteria
  • Ricketssia-like bacteria that multiply inside white blood cells
  • Deer tick is the vector

• Rickettsias cause typhus diseases
  • Obligate intracellular Gram negative rods parasitizing eukaryotes
  • Spread by arthropods
• Three main kinds
  1. Epidemic typhus
  2. Endemic murine typhus
  3. Rocky Mountain spotted fever

• Caused by Francisella tularensis
  • Gram negative, facultatively anaerobic, pleomorphic rod
  • Found in rabbits (zoonosis); low ID₅₀
  • Survives in phagocytes
    • Treatment must take this into consideration (prolonged administration of streptomycin/gentamicin)
• Portal of entry determines disease form
  • Skin/mucous membrane abrasion
    • Local inflammation
    • Small ulcer at site of infection
    • Regional lymph nodes enlarge, fill with pus
    • Septicemia and pneumonia develop
  • Ingestion of inadequately cooked meat causes infection focus in mouth/throat
  • Arthropod bite (e.g., deer flies, ticks, rabbit lice)

1. Small, aerobic, Gram negative pleomorphic rods
2. OBLIGATE intracellular parasites
3. Cannot be cultured on normal bacteriology media (WHY???)
   • To isolate, requires tissue culture cells or laboratory animals
   • Diagnosis depends heavily upon serological testing
4. Considered normal flora for arthropods
5. Zoonotic pathogens that disseminate in the blood to other organs
   • From the portal of entry in the skin, rickettsiae spread to infect the endothelium and sometimes the vascular smooth muscle cells
   • Rickettsia species enter their target cells, multiply by binary fission in the cytosol, and damage heavily parasitized cells directly

Puerperal sepsis

• AKA childbirth fever or postpartum endometritis
• Nosocomial infection
• Portal of entry is the uterus, becoming a peritonitis and septicemia if unchecked
  • Childbirth
  • Abortion
• Most common etiologic agents
  • Group A beta hemolytic Streptococcus
  • non-Group A Streptococcus
  • Gram negative rods
• To diagnose: Blood cultures
• To prevent: wash hands; disinfect instruments
• To treat: penicillin

Viral Diseases of the Cardiovascular and Lymphatic Systems (pages 403 and 418)

1. Burkitt’s Lymphoma
   • Epstein Barr virus (human herpesvirus 4) in conjunction with a pre-existing malarial infection
   • Most common childhood cancer in Africa
2. Infectious Mononucleosis
   • Epstein Barr virus
   • More serious in young adults
   • High incidence among upper socioeconomic college populations
3. Nasopharyngeal Carcinoma
   • Epstein Barr virus
   • Major cause of death in Southeast Asia
4. Viral Hemorrhagic Fevers

Cytomegalovirus

• Infects salivary glands, epithelium, and liver
• Symptoms include fever, malaise, enlarged spleen
• In pregnant women, may cause serious congenital disease if it enters fetal bloodstream
• More serious in the immunocompromised

1. Yellow fever
2. Dengue
3. Marburg
4. Ebola
5. Lassa
6. Argentine
7. Bolivian
8. Hanta
9. All are caused by enveloped, RNA viruses
10. Natural reservoir is an animal or insect host
    • Humans are infected when they come in contact with natural host ("index" case)
    • Once infected, humans can transmit some of these viruses among themselves
      • Examples are Ebola, Marburg, and Lassa
11. Many cause severe, life-threatening disease
12. Except for Dengue and Yellow fever, all are biosafety level 4 viruses

Protozoan and Helminthic Diseases of the Cardiovascular and Lymphatic Systems

1. American Trypanosomiasis
2. Leishmaniasis
3. Toxoplasmosis
4. Malaria
5. Babesiosis
6. Schistosomiasis
   • This is caused by a Helminth

• Trypanosoma cruzi
• Euglenozoan, hemoflagellate
  • Flagellated protozoan
  • No sexual reproduction
• Reservoir is wild animals such as rodents, opossums, armadillos
• Found in southern Texas, Central and South America
• Reduviid bug is the vector
  • It bites its victim and then defecates into the wound, transmitting the pathogen
• Organism multiplies intracellularly
• Damages heart

• Also a Euglenozoan hemoflagellate, Leishmania species
  • Many species, although 3 main groups
  • Cause visceral, cutaneous, and mucocutaneous forms of disease
  • Small mammals are the reservoir
• Transmitted through the bite of the female sandfly (vector)
• This disease is also communicable, in that direct contact with an active lesion can transmit the infection

• Toxoplasma gondii, an Apicomplexan
  • Not motile; obligate intracellular parasites; complex life cycles that include intermediate and definitive hosts
  • Organisms that cause malaria and babesiosis belong to this group as well
• Disease is acquired through ingestion of undercooked meats or from cat feces
• Is especially dangerous to pregnant woman’s fetus (results in stillbirth or neurological damage)
• In most people, symptoms are mild
  • If immunocompromised, neurological damage may occur

• Plasmodium, also an Apicomplexan
• Three species of Plasmodium produce 3 types of malaria
• Vector is Anopholes mosquito
  • Plasmodium sporozoites are produced through sexual reproduction of the gametocyte stage of the organism in the mosquito
  • When the mosquito bites man, sporozoites are injected
  • Sporozoites undergo schizogony in the human red blood cells, producing merozoites
  • They reproduce asexually
  • A few will develop into male or female sexual forms called gametocytes
    • Within the human host, nothing more will happen
    • BUT, if the Anopholes takes a blood meal, they will mate within the mosquito’s intestine, to form a zygote, which produces sporozoites

• This protozoan disease is carried by the same ticks that carry the bacterial diseases
  • Babesia microti, also an apicomplexan
  • Organism infects red blood cells
  • Found in Massachusetts, Connecticut, and New York
• More serious in immunocompromised people

• Small fluke, Schistosoma species, is etiologic agent
  • Three types, causing 3 different diseases
  • Recall that flukes, or Trematodes, are Platyhelminthes ("flatworms")
• Man is definitive host (adult parasite)
  • Excretes eggs in feces/urine
  • Eggs hatch in water, releasing larva (miracidia)
  • The larva penetrate the snail, the intermediate host, where they form cercariae
  • When cercariae are released, they are infective to man, penetrating his skin