module 2: clinical scenario tuberculosis Flashcards
when did the organism of tuberculosis start to flourish?
when our ancestor transitioned away from being hunter-gatherers to living under more crowded conditions
what organism is tuberculosis caused by?
mycobacterium tuberculosis
what is special about the morphology of mycobacterium tuberculosis and how it affects the gram stain
unique outer coating that doesn’t take up the stain used to identify bacteria
where does M. tuberculosis thrive?
places where levels of oxygen is high –> lungs
how does M. tuberculosis spread?
air droplets when affected patients cough, sneeze, or speak in confined spaces
what are symptoms caused by M. tuberculosis?
chronic coughing
fever
blood-tinged sputum
loss of appetite
severe weight loss
when people die of tuberculosis, what is used to identify the disease?
hard nodules, tubercules, were found in the lungs
why did people in the 1800s think tuberculosis was an inherited disease?
adults unknowingly spread it to people in closest proximity to them and their children
what are Koch’s postulates?
four principles that had to be true before an organism could be considered the cause of a disease
list Koch’s postulates
- organism had to be present in every case of disease
- organism had to be isolated from the patient with the disease and grown in pure culture
- organisms taken from the pure culture had to cause the disease in healthy laboratory animals
- organism had to be isolated from animal and identified as same organism that was taken from patient
describe the pathogenesis of M. tuberculosis
- inhaled into lungs and phagocytosed by cells living within alveoli
- macrophages engulf bacteria into membrane-lined vesicle and fuse that vesicle with another that contains acidic enzymes to kill bacteria
list and describe three ways in which M. tuberculosis protects itself against the body’s acidic enzyme system
- mycolic acids -> hydrophobic, they increase the bacterium’s resistance to degradation by enzymes that work best in aqueous environments
- ways to prevent the two vesicles from fusing while simultaneously allowing vesicle containing bacteria to fuse with different vesicles containing nutrients
- covers itself with substance that acts as antacid to counteract acidic environment of vesicle holding enzymes
what kind of infection is the dormant period where people are symptom free and don’t infect others?
latent
what are percolators?
patients that may have clinical problems on the horizon
what are places the organism can survive once it breaks out of the macrophage and go dormant?
pulmonary tissue
local lymph nodes that drain the affected part of lung
bloodstream
what are other organs besides the lungs that tuberculosis can affect?
bones
joints
tissue surrounding brain
what is active tuberculosis?
patients will have symptoms for consumption
after a few weeks of active infection, how does the body respond and what is the end result?
- body sends variety of white blood cells to infected pulmonary tissue
- end results in formation of large, thick capsules around infected alveolar macrophages and damaged tissue
what are granulomas and what is their function?
- thick white capsules that either protect M. tuberculosis from immune response or protect the rest of the body from dissemination of bacteria
what happens to granulomas after the tissue is damaged?
center dies and takes on soft white texture of cheese
what is the mortality rate of tuberculosis?
70%, top ten causes of death worldwide
what kind of drug is isoniazid?
antibacterial
how does isoniazid work?
inhibits the synthesis of some special components that make up the bacteria’s thick cell wall and as a result, kills M. tuberculosis that are actively dividing in people with active tuberculosis as well as slow growing bacteria in patients with latent tuberculosis
what cells have enzymes that metabolize when drugs are administered?
hepatocytes
where can the enzymes of hepatocytes be found?
smooth ER or cytosol
where is N-acetyltransferase present in?
cytosol of hepatocytes
some cells of small intestines
how does acetyltransferase function?
transferring acetyl groups to the drug being metabolized
how does the body metabolize isoniazid?
N- acetyltransferase transfers acetyl group from acetyl CoA to isoniazid to form acetylisoniazid, which is inactive against M. tuberculosis
when dis isoniazid reach its highest blood concentration?
~ 30 minutes
what was the elimination half-life of isoniazid?
little more than 1.5 hours
what is elimination half life?
time it takes for blood concentration to decrease by 50%
what did it mean when the elimination half life of isoniazid of the three groups was 1 hour (bottom of graph)?
they metabolized isoniazid much faster than people in the top group
the opposite is true for the top group
which of the three groups that metabolized isoniazid is the blood concentration much higher?
the top group
The activities of the _________________enzyme were different among the three groups of patients.
N-acetyltransferase
match the three groups that metabolized isoniazid to ineffective, effective, and toxic and what this means
bottom line- ineffective: fast acetylators
middle line- effective: intermediate acetylators
top line- toxic: slow acetylators
