module 2: clinical scenario tuberculosis

Question 1

when did the organism of tuberculosis start to flourish?

Answer 1

when our ancestor transitioned away from being hunter-gatherers to living under more crowded conditions

Question 2

what organism is tuberculosis caused by?

Answer 2

mycobacterium tuberculosis

Question 3

what is special about the morphology of mycobacterium tuberculosis and how it affects the gram stain

Answer 3

unique outer coating that doesn’t take up the stain used to identify bacteria

Question 4

where does M. tuberculosis thrive?

Answer 4

places where levels of oxygen is high –> lungs

Question 5

how does M. tuberculosis spread?

Answer 5

air droplets when affected patients cough, sneeze, or speak in confined spaces

Question 6

what are symptoms caused by M. tuberculosis?

Answer 6

chronic coughing
fever
blood-tinged sputum
loss of appetite
severe weight loss

Question 7

when people die of tuberculosis, what is used to identify the disease?

Answer 7

hard nodules, tubercules, were found in the lungs

Question 8

why did people in the 1800s think tuberculosis was an inherited disease?

Answer 8

adults unknowingly spread it to people in closest proximity to them and their children

Question 9

what are Koch’s postulates?

Answer 9

four principles that had to be true before an organism could be considered the cause of a disease

Question 10

list Koch’s postulates

Answer 10

1. organism had to be present in every case of disease
2. organism had to be isolated from the patient with the disease and grown in pure culture
3. organisms taken from the pure culture had to cause the disease in healthy laboratory animals
4. organism had to be isolated from animal and identified as same organism that was taken from patient

Question 11

describe the pathogenesis of M. tuberculosis

Answer 11

• 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

Question 12

list and describe three ways in which M. tuberculosis protects itself against the body’s acidic enzyme system

Answer 12

1. mycolic acids -> hydrophobic, they increase the bacterium’s resistance to degradation by enzymes that work best in aqueous environments
2. ways to prevent the two vesicles from fusing while simultaneously allowing vesicle containing bacteria to fuse with different vesicles containing nutrients
3. covers itself with substance that acts as antacid to counteract acidic environment of vesicle holding enzymes

Question 13

what kind of infection is the dormant period where people are symptom free and don’t infect others?

Answer 13

latent

Question 14

what are percolators?

Answer 14

patients that may have clinical problems on the horizon

Question 15

what are places the organism can survive once it breaks out of the macrophage and go dormant?

Answer 15

pulmonary tissue
local lymph nodes that drain the affected part of lung
bloodstream

Question 16

what are other organs besides the lungs that tuberculosis can affect?

Answer 16

bones
joints
tissue surrounding brain

Question 17

what is active tuberculosis?

Answer 17

patients will have symptoms for consumption

Question 18

after a few weeks of active infection, how does the body respond and what is the end result?

Answer 18

• 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

Question 19

what are granulomas and what is their function?

Answer 19

• thick white capsules that either protect M. tuberculosis from immune response or protect the rest of the body from dissemination of bacteria

Question 20

what happens to granulomas after the tissue is damaged?

Answer 20

center dies and takes on soft white texture of cheese

Question 21

what is the mortality rate of tuberculosis?

Answer 21

70%, top ten causes of death worldwide

Question 22

what kind of drug is isoniazid?

Answer 22

antibacterial

Question 23

how does isoniazid work?

Answer 23

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

Question 24

what cells have enzymes that metabolize when drugs are administered?

Answer 24

hepatocytes

Question 25

where can the enzymes of hepatocytes be found?

Answer 25

smooth ER or cytosol

Question 26

where is N-acetyltransferase present in?

Answer 26

cytosol of hepatocytes
some cells of small intestines

Question 27

how does acetyltransferase function?

Answer 27

transferring acetyl groups to the drug being metabolized

Question 28

how does the body metabolize isoniazid?

Answer 28

N- acetyltransferase transfers acetyl group from acetyl CoA to isoniazid to form acetylisoniazid, which is inactive against M. tuberculosis

Question 29

when dis isoniazid reach its highest blood concentration?

Answer 29

~ 30 minutes

Question 30

what was the elimination half-life of isoniazid?

Answer 30

little more than 1.5 hours

Question 31

what is elimination half life?

Answer 31

time it takes for blood concentration to decrease by 50%

Question 32

what did it mean when the elimination half life of isoniazid of the three groups was 1 hour (bottom of graph)?

Answer 32

they metabolized isoniazid much faster than people in the top group

the opposite is true for the top group

Question 33

which of the three groups that metabolized isoniazid is the blood concentration much higher?

Answer 33

the top group

Question 34

The activities of the _________________enzyme were different among the three groups of patients.

Answer 34

N-acetyltransferase

Question 35

match the three groups that metabolized isoniazid to ineffective, effective, and toxic and what this means

Answer 35

bottom line- ineffective: fast acetylators
middle line- effective: intermediate acetylators
top line- toxic: slow acetylators