Wednesday, August 23, 2017

Infections of the Blood

Another week, another set of diseases! I think this is the last week that we're getting infodumped about diseases- future lectures seem to cover stuff related to diagnosis and treatment. Remember: red pathogens are found in Microbe Invader (http://microbeinvader.com).

This lecture started with a bit of anatomy about the cardiovascular system. All you really need to know is that it delivers blood around the body, and that plasma can diffuse out of the capillaries and get picked up by the lymph system. The lymph system later dumps its crap back into the venous system. If you want to know more details regarding the cardiovascular system, just use the search function on this blog. I wrote a fair bit about the anatomy in ANHB2212, and a lot about the physiology in PHYL3002.

Bacterial Infections

Sepsis and Septic Shock

Sepsis is defined as "a toxic inflammatory condition arising from the spread of bacteria or bacterial toxins from the focus of infection." Septicaemia is basically sepsis that results from bacteria in the blood. (Bacteria in the blood, with or without sepsis, is also known as bacteraemia.) Low-level bacteremia is usually okay as our host defensive cells can kill bacteria, and the low levels of iron in our blood are generally insufficient to sustain bacterial growth, but when our defences fail, or when organisms are pathogenic, we might have some problems.

Sepsis can be divided up into three main stages. In the first stage of sepsis, inflammation occurs and cytokines are released, resulting in fever, chills, accelerated breathing and faster heart rate. In the second stage, severe sepsis, at least one organ is damaged. In the third stage, septic shock, there is a significant drop in blood pressure due to inflammation. Septic shock can lead to organ failure and death.

Some of the most frequent causes of sepsis are Neisseria meningitidis, as well as Staphylococcus, Streptococcus and Enterococcus species. In fact, Enterococcus species are some of the leading causes of nosocomial (hospital-acquired) sepsis- they enter the body during invasive procedures, such as dialysis. Septic shock is more likely to be caused by gram-negatives, such as N. meningitidis, as they release endotoxins when they die. The inflammatory response leads to a drop in blood pressure. N. meningitidis septicaemia is also known as meningococcal disease, which is a pretty nasty disease that can be fatal within hours. Septic shock can also be caused by gram-positive bacteria such as Staphylococcus and Streptococcus. They produce potent exotoxins (remember, gram-positive bacteria can't produce endotoxins) called superantigens (i.e. antigens that induce a really strong immune response). This form of septic shock is also called toxic shock syndrome.

Puerperal Sepsis

Puerperal sepsis is also known as "childbirth fever," as it is an infection of the uterus following childbirth or abortion. The infection can spread from the uterus to the abdominal cavity, causing peritonitis and then sepsis. The most common cause is Streptococcus pyogenes. Puerperal sepsis is pretty rare in developed countries, but it is still a leading cause of maternal death in developing countries.

Bacterial Endocarditis

Endocarditis refers to inflammation of the endothelium, which is the innermost of the layers lining the heart (see here for details). There are two main types of endocarditis: subacute and acute.

Subacute endocarditis is usually caused by alpha-haemolytic streptococci in the oral cavity. Bacteria can lodge in pre-existing lesions in the heart, where they become trapped in clots. These clots protect the bacteria from phagocytes, while they get to work destroying the heart. Untreated subacute endocarditis is fatal within months. Risk factors for subacute endocarditis include congenital heart defects, syphilis, or rheumatic fever.

Acute endocarditis is usually caused by our good friend S. aureus. As its name suggests, it progresses more rapidly than subacute endocarditis. It destroys heart valves and, if untreated, kills within days.

Rheumatic fever

See previous post: Carditis

Tularaemia

Tularaemia is caused by F. tularensis, which is a gram-negative rod. It is pretty rare and is usually passed around by infected animals, particularly rabbits and squirrels (as such, it is more common in the USA). It causes ulcers and enlarged, pus-filled lymph nodes.

Brucellosis (undulant fever)

Brucellosis is caused by Brucella species, which grows inside cells. When cultured, it requires enrichment and elevated carbon dioxide. The major species are B. melitensis, B. abortus and B. suis. B. melitensis, which usually affects goats and sheep, can cause severe disease and death in humans. B. abortus, which infects livestock, causes more mild disease, while B. suis, found in swine and cattle, causes ulcers in humans. Other symptoms of Brucella infection include chills, fever, malaise, and sweating. Brucella is transmitted via contact with diseased animals, such as via abrasions in the skin or by drinking unpasteurised milk. Treatment is with long-term tetracycline and streptomycin.

Anthrax

Anthrax is caused by Bacillus anthracis, which is a gram-positive, endospore-forming rod. It is found in soil and affects grazing animals, such as cattle and sheep. There are three main types of anthrax: cutaneous, gastrointestinal, and inhalational. However, only inhalational anthrax enters the bloodstream. When endospores enter the bloodstream, they are taken up by macrophages, where they germinate into vegetative cells. This causes the macrophage to die, releasing bacteria, which then replicate rapidly and secrete toxins. B. anthracis secretes two toxins: oedema toxin and lethal toxin. These toxins share a component called protective antigen, which binds toxins to host cells.

One of the tricky things about B. anthracis is that its capsule is made out of amino acids, not polysaccharides (like most bacterial capsules). As such, protective immunity is not stimulated, and people generally do not acquire immunity to anthrax.

Viral Infections

Infectious mononucleosis (Mono/Glandular Fever)

Infectious mononucleosis is caused by the Epstein-Barr Virus (EBV). Children are often infected by EBV without showing symptoms. However, if EBV is contracted as a young adult, disease can occur. It is usually self-limiting and non-fatal, with symptoms such as fever, fatigue, and sore throat. However, deaths can occur due to rupture of the spleen. EBV is transmitted through saliva, which is why this disease is sometimes known as the "Kissing Disease."

Cytomegalovirus (CMV) 

CMV is actually a type of herpes virus- HHV5 (human herpes virus 5). Nearly all humans are infected with CMV at some point, but it usually causes no or mild symptoms. In the immunocompromised, however, CMV can cause life-threatening pneumonia, and many AIDS patients develop CMV retinitis (blindness due to CMV infection). A foetus may also suffer damage if a pregnant mother acquires CMV for the first time during pregnancy.

CMV is a very sneaky virus. It can remain latent in our white blood cells, and move between cells that are in contact with each other, in order to escape detection by the immune system. CMV can't hide from microscopes, though- they form distinctive inclusion bodies that are known as "owl's eyes."

Yellow fever

Yellow fever is transmitted by mosquitoes, particularly in tropical areas of Africa and Central and South America. It causes fever, chills, headache, nausea, vomiting, and jaundice (which is where the disease gets its name).

Dengue fever

Dengue fever is caused by Dengue virus, which is also transmitted by mosquitoes. Once again, it is endemic in tropical areas. Its symptoms can include fever, severe chills, joint pain and rash. It is usually quite mild, though some people can experience severe pain, giving this disease the nickname of "breakbone fever." There is, however, a more dangerous form called dengue haemorrhagic fever, which is more likely to occur if you have multiple Dengue fever infections in a row.

Emerging viral haemorrhagic fevers

Yellow fever and Dengue fever are known as "classic" haemorrhagic fevers, as we've known about them for a long time. Marburg virus, Ebola virus and Lassa virus also cause haemorrhagic fevers, but as we've only found out about them in the past 50 years or so, they're considered to be "emerging" haemorrhagic fevers. Marburg virus was discovered from African monkeys that were imported into Europe, Lassa virus was found to be from rodents, and Ebola is possibly from fruit bats (though we don't know for certain).

AIDS

See previous post: Chemotherapy III: Antiviral Drugs

Burkitt's Lymphoma

Burkitt's lymphoma is a jaw tumour that seems to result from infection by EBV and malaria. It is possible that malaria infection impairs the immune response to EBV.

And that's the last post covering content for next week's test! (CNS infections are up next, but I don't think they're on the test. Weird.)

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