Exam 4 - Lecture 6 Flashcards
1
Q
Describe polio
A
Polio was described as a huge thing in the 60s. It is a neuromuscular infection that messed up neuromuscular transmissions. It caused the central nervous system to be unable to talk to the skeletal muscles.
2
Q
What were the effects of polio on individuals?
A
For some people, polio was very bad, causing loss of control of almost all skeletal muscles. For others, it was more limited.
3
Q
How can one manipulate the controls of the iron lung?
A
It was believed the person could manipulate some controls on the iron lung from inside.
4
Q
When did vaccines for polio develop, and how were people feeling about the disease around that time?
A
Dr. Schmidt believes vaccines were developed in the 60s, but acknowledges dates might be wrong. People were really scared of polio in the 50s and 60s.
5
Q
Who was mentioned as being particularly affected by polio?
A
Kids
6
Q
What was unknown about polio before its cause was identified and how long did it take?
A
People couldn’t figure out where the disease was coming from or how it was spreading. For about 20 years, they couldn’t figure out what was going on.
7
Q
What were the primary ways to design vaccines discussed in the source (back then)?
A
One using a dead virus and another using a less potent live virus.
8
Q
Describe the method using a dead virus for vaccine development.
A
One method involved growing virus in a lab, killing it, and injecting the dead virus so the immune system would recognize it and build antibodies. This method worked out pretty well initially.
9
Q
Describe the method using a less potent live virus for vaccine development.
A
Engineering the virus to be just less potent.
10
Q
How effective were the two early polio vaccines?
A
For a while, there were two vaccines, both very effective, maybe around 99% effective. Significant because hardly any vaccines are that effective.
11
Q
What significant safety incident occurred with one of the polio vaccines?
A
A safety incident occurred where a batch of the dead virus vaccine was contaminated with live virus. They grew a bunch in the lab, thought they had killed it, but it was not dead.
12
Q
What were the consequences of the polio vaccine safety incident? Which type of vaccine was it?
A
They ended up injecting about 10,000 people with live virus. A lot of people got hurt really bad. A lot of them ended up in the iron lung. Because of this incident, they pulled the dead virus vaccine off the market.
13
Q
Which polio vaccine became the standard after the safety incident?
A
They went with the weakened/engineered live virus vaccine as the standard. Dr. Schmidt thinks this is the form still used today.
14
Q
What downside do people often relate to vaccines, according to the source?
A
People always relate the downsides to things like the autism rate.
15
Q
How was the polio virus infection traced and spread?
A
The infection was traced back to swimming pools and school pools as a source of infection. It happened typically during times of the year when students had swimming lessons.
16
Q
How was polio eliminated?
A
Polio was pretty much eliminated soon after the vaccine was released.
17
Q
Where is polio still present today?
A
It is still present in third-world countries.
18
Q
What is the reason why there is not a lot of polio floating around nowadays?
A
Nowadays, people might say there’s not a lot of polio floating around, but there’s a reason for that: the vaccine.
19
Q
What charity was mentioned in the context of polio and public health?
A
The role of charities like the March of Dimes in raising awareness and funds is discussed.
20
Q
What was the origin of the March of Dimes charity?
A
It started as a campaign to do research to find a way to beat the polio virus.
21
Q
How did the March of Dimes raise money?
A
They had big campaigns where you would put a dime in an envelope and sent it to the charity. This was back when postage wasn’t 80 times the cost of the donation. It was a big campaign for people to save up their dimes from loose change and send them. The charity ended up raising lots and lots of money.
22
Q
What was mentioned as a success in medical research, similar to the effort against polio?
A
Dr. Schmidt mentions the success of childhood cancer research.
23
Q
What was the mortality rate for childhood cancer in the past?
A
Childhood cancer used to be incredibly dangerous with very high mortality rates.
24
Q
What are the current treatments for many childhood cancers, and what is the survival rate?
A
Nowadays, a lot of childhood cancers are being beaten with a combination of drugs, radiation, chemo, and bone marrow transplants. The survival rate is believed to be like 90% somewhere around there, which is incredibly high.
25
What was said about tackling adult cancer?
If tackling adult cancer were prioritized, it certainly could be done, but there's only so much money.
26
Define emphysema according to the source.
Emphysema is a disease where the inside of the lungs are basically shredded.
27
What is a result of the lungs being shredded in emphysema?
This results in lower surface area for gas exchange.
28
Explain lung compliance in the context of emphysema.
In emphysema, the lungs become more compliant (easier to fill). However, they become harder to empty.
29
What happens to alveoli in COPD and emphysema?
COPD involves losing alveoli. Alveoli are arranged next to each other. In emphysema, there can be a merger of alveoli, resulting in larger alveoli.
30
What happens to the walls of merged alveoli in emphysema?
The walls of these merged alveoli often have less recoil.
31
Why are larger alveoli problematic in emphysema?
Larger alveoli are harder to empty, leading to breathing difficulties.
32
What happens to the lung overall if emphysema happens across the entire lung?
If this happens across the entire lung, a lot of alveoli are lost, along with some elastic tissue. The large, fused alveoli are hard to get air out of. Over time, the lung looks more like the picture described and gets bigger, which is not good for breathing.
33
Describe the role of digestive enzymes in the lungs.
These enzymes are probably set up to destroy things that shouldn't be in the lungs, such as bacteria or crud from infections. They help remove debris, break it down, and eliminate fluid problems.
34
How can destroyed cells affect fluid problems in the lungs?
Destroyed cells releasing proteins can affect interstitial protein osmotic pressure, leading to fluid problems.
35
What does the source say about the presence and activity of this digestive system in the lungs?
The lungs have a built-in digestive system to destroy stuff that shouldn't be there. This system is always active, even if its low activity.
36
What type of enzyme is the version found in the lungs?
The enzyme version in the lungs is a version of trypsin.
37
What is the normal activity level of trypsin in the lungs, and why is this important?
Normally, this activity is on the low end. We don't want this enzyme running wild, potentially chewing up the 'rubber bands' or 'springs' (elastic tissue) in the lungs. We want trypsin there, but not roaming and destroying every protein if not needed.
38
What molecule inhibits trypsin in the lungs most of the time?
There is a molecule that inhibits trypsin most of the time when it's not needed. This compound is called Alpha One antitrypsin.
39
Where does Alpha-1 antitrypsin come from and how does it get to the lungs?
Created in the liver and then put into blood and carried to the lungs.
40
What happens if the gene for Alpha One antitrypsin doesn't work, or the molecule isn't there?
If the gene doesn't work, the molecule doesn't work, or it's just not there, trypsin activity would switch over into being very high.
41
How does high trypsin activity affect the lungs?
High trypsin activity might start chewing up these springs (stretchy proteins like lung walls), causing the loss of recoil pressure or force in the lungs.
42
What is high trypsin activity compared to by Dr Schmidt?
Trypsin going out of control and chewing up stuff it shouldn't be is like an autoimmune disorder where antibodies destroy things they shouldn't.
43
What are some causes discussed for Alpha One antitrypsin impairment?
Inherited disorders, smoking and liver problems.
44
What is the prevalence of genetic deficiency in Alpha One antitrypsin?
About one in every 3,000 people have a genetic deficiency in Alpha One antitrypsin. They just don't make it or make a version that doesn't work.
45
What is typically the result of Alpha One antitrypsin deficiency?
Emphysema.
46
What is the prognosis for Alpha One antitrypsin deficiency?
Without a lung transplant, this deficiency is probably going to lead to death at about 30 years of age. In some folks, death happens earlier.
47
Why are people with Alpha One antitrypsin deficiency usually good transplant candidates?
These people are usually good transplant candidates because they didn't destroy their lungs themselves; it wasn't a behavior thing. You don't have to worry about them getting fresh lungs and going back to smoking 10 packs a day.
48
How does smoke impair Alpha One antitrypsin activity?
Smoke can inhibit the action of alpha-1 antitrypsin.
49
Why are super small particles from smoke a problem for the lungs' filtering system?
Super small particles from smoke are too small to get caught in the mucus in the nose. The nose filters larger particles by spinning air and making it take a hairpin turn, slamming particles into sticky mucus. This system works great for filtering relatively small things, but smoke is too small. Smoke doesn't have enough mass or inertia to be adequately captured by mucus.
50
What is the direct effect of smoke on Alpha One antitrypsin?
Bringing smoke into the lungs is a chemical inhibitor of alpha one antitrypsin. It just blocks its activity.
51
How do liver problems relate to Alpha One antitrypsin deficiency?
The liver is the source of alpha one antitrypsin.
52
What can cause liver problems that affect Alpha One antitrypsin?
Liver problems could be congenital or due to alcoholism.
53
What old habit was mentioned related to liver function and smoking?
A long time ago, people used to smoke a lot. You would see people chain-smoking at bars while drinking. The reason was that alcohol turns on the liver, including metabolizing nicotine. Someone drinking heavily burns through nicotine very fast, making them smoke an awful lot.
54
What type of therapy does Dr. Schmidt think Alpha One antitrypsin deficiency would be a good target for?
Dr. Schmidt thinks Alpha One antitrypsin deficiency would likely be a good target for gene therapy.
55
How is Alpha One antitrypsin deficiency similar to cystic fibrosis in terms of genetic therapy?
Genetic therapy is similar to the approach for cystic fibrosis. Cystic fibrosis is also a lung disorder, resulting from one gene mutation. Alpha One antitrypsin deficiency involves just one gene being messed up. Easier if only one gene!
56
What is mentioned as a potential way to provide Alpha One antitrypsin?
Dr. Schmidt assumes that one could isolate this stuff from people and provide it intravenously.
57
What is the situation regarding Alpha One antitrypsin deficiency for patients who receive lung transplants?
Patients who receive lung transplants for Alpha One antitrypsin deficiency still have the deficiency and are still losing new lung tissue.
58
What is the desired state of iron in hemoglobin for oxygen transport?
The desired state of iron is ferrous (Fe2+) with two positive charges.
59
What is the function of ferrous iron in hemoglobin?
Ferrous iron is capable of temporarily binding and later releasing oxygen. This is the 'good' version of iron.
60
What process can lead to the conversion of ferrous to ferric iron?
Oxidative stress.
61
How does oxidation typically affect electrical charge?
Oxidation typically involves removing an electron, which is like adding a positive charge.
62
What is the oxidized state of iron in hemoglobin, and what is its charge?
The oxidized iron is ferric (Fe3+), which has three positive charges.
63
What is the function of ferric iron in hemoglobin?
Ferric iron typically can't release oxygen; it might bind permanently.
64
What is the consequence of oxygen binding permanently to hemoglobin?
If oxygen binds permanently, it takes up a spot for other oxygens and can't be released where needed.
65
What is the normal percentage of circulating hemoglobin in the ferric form?
Typically, about 1.5% of circulating hemoglobin is in the ferric form.
66
Why is normal arterial hemoglobin saturation not 100%?
Part of the reason is venous admixture from bronchial circulation mixing with oxygenated blood (believed to mix in the left atrium). Another reason is that a portion of hemoglobin is almost always in a state where it can't do a lot of work; the 1.5% of ferric iron is baked into the 97.4% number.
67
What enzyme handles the reduction of ferric iron back to ferrous iron? What is the process called?
An enzyme called methemoglobin reductase is in charge of reducing ferric iron back to ferrous iron. This is a reduction process.
68
What is another name for hemoglobin with ferric iron?
Another name for hemoglobin with this 'bad iron' is methemoglobin.
69
How does methemoglobin reductase restore hemoglobin function?
The enzyme methemoglobin reductase is capable of removing a positive charge (or adding an electron) to reduce the charge from 3+ to 2+. This restores or resets hemoglobin as it's being oxidized.
70
How many chains does typical hemoglobin have, and what are they in adults?
Hemoglobin typically has four different chains. Adult hemoglobin has two alpha chains and two beta chains.
71
How many oxygen molecules can each hemoglobin chain carry? How many atoms?
Each chain can carry one O2 molecule, but every O2 molecule has TWO oxygen ATOMS. Therefore, one hemoglobin can carry 4 oxygen molecules, or 8 oxygen atoms.
72
What part of the hemoglobin is affected in sickle cell anemia?
Sickle cell anemia is a result of having defective beta chains.
73
How are the genes for hemoglobin chains passed down?
Parents.
74
What is the sickle trait?
If you receive one defective beta gene, consistent with sickle cell anemia, you have the sickle trait. Having one bad beta gene (e.g., from dad, with a good version from mom) results in sickle cell trait.
75
How many oxygen molecules can hemoglobin carry?
Hemoglobin can carry 4 oxygen molecules, or 8 oxygen atoms.
76
What is the sickle trait?
If you receive one defective beta gene, consistent with sickle cell anemia, you have the sickle trait. Having one bad beta gene (e.g., from dad, with a good version from mom) results in sickle cell trait, but not necessarily full blown anemia.
77
What is full-blown sickle cell disease?
If you have two defective beta chains, that's full-blown sickle cell disease.
78
What is the core mechanism causing problems in sickle cell disease?
Hemoglobin gets stuck in the capillaries.
79
Describe how red blood cells move through capillaries.
As blood cells move through capillaries, they barely fit; the capillary internal diameter is less than the red blood cell diameter. Red blood cells must be flexible to get through capillaries.
80
What is a potential benefit of red blood cells barely fitting in capillaries when healthy?
It's probably good that they barely sneak through when healthy, as the red blood cell walls are against capillary walls, reducing fluid in the way for gas exchange.
81
What triggers the shape change in red blood cells with defective sickle hemoglobin?
As oxygen is unloaded, the shape of the red blood cell changes into the sickle version. Deoxygenation causes this change in anatomy and makes the red blood cell rigid and curved, causing it to get stuck.
82
Is sickling painful?
Extremely painful and crippling. Pain is probably one of the worst things about the disease.
83
What happens to a capillary if a sickled red blood cell is jammed in it?
Capillary may die.
84
What are the consequences of a blocked capillary due to sickling?
Until the jammed cell goes away and a new capillary is built, it's problematic because tissue can't get blood or nutrients through the blocked capillary. It has to look for nutrients elsewhere (collateral circulation).
85
How can someone with sickle cell trait reduce the disparity of the trait? Why?
If you have the sickle cell trait, one way to reduce the disparity of the trait is to limit activity. Keeping metabolism low means not pulling as much oxygen from red blood cells.
86
What is the net result of sickled red blood cells?
The net result is that sickled red blood cells are taken out of circulation, and the body has to build new ones, leading to the anemia term.
87
How much oxygen is typically unloaded from blood in the periphery at rest?
At rest, blood unloads about 5 mls of O2 from each deciliter in the periphery. At this level, you typically don't see much sickling.
88
What level of oxygen unloading was mentioned as an example during exercise?
An example is pulling 12 mls of O2 from each deciliter during exercise, which is more than twice normal.
89
What is one potential treatment option for sickle cell disease mentioned that is not very effective?
Supplemental oxygen can be useful for some people to limit sickling but it's not all that effective because oxygen is insoluble. Supplementing oxygen doesn't raise oxygen content very much, limiting its effectiveness.
90
What is another treatment option for full-blown sickle cell disease? What are the challenges and risks?
For full-blown disease, one treatment option is to replace red blood cells with donor cells via blood transfusion. You would have to transfuse an awful lot of blood. Blood is limited. Massive transfusions can be viable but sometimes problematic due to blood supply issues. Transfusions have risks, including the body rejecting new cells or infectious agents in the transplanted blood.
91
What drug treatment is mentioned for sickle cell disease, and how does it work?
Hydroxyurea. Hydroxyurea basically turns on some fetal hemoglobin genes.
92
What is the difference between fetal and adult hemoglobin chains?
The difference between fetal and adult hemoglobin is that fetal hemoglobin has gamma subunits instead of beta subunits.
93
When do beta subunits typically show up?
Right after birth.
94
Are the genes for fetal hemoglobin still in our DNA?
Typically, the fetal body switches over after birth, but the genes for fetal hemoglobin are still in our DNA.
95
Besides oxygen delivery issues, what other major problem is mentioned in sickle cell disease?
CO2 ends up being a problem just as big as oxygen delivery. If oxygen can't be unloaded, tissues switch to anaerobic metabolism, generating lots more 'non-volatile' acids.
96
Why is the sickle mutation conserved and fairly common?
Having the trait gives people a survivability uptick with malaria.
97
Does the source state whether people with full-blown sickle cell disease are resistant to malaria?
Dr. Schmidt doesn't know if people with full-blown disease are resistant to malaria.
98
What other version of hemoglobin was mentioned that uses oxygen, and where is it typically found?
Myoglobin was spoken about earlier; it's another version of hemoglobin that uses oxygen. It uses iron to pull oxygen into tissues where needed, typically skeletal muscle.
99
What are some other versions of hemoglobin mentioned besides adult hemoglobin and myoglobin?
Other versions include acetylated hemoglobin and Hemoglobin A1c (HbA1c). Another version is carboxyhemoglobin (hemoglobin occupied by carbon monoxide).
100
What causes Hemoglobin A1c levels to rise?
Sugars are sticky and get stuck to things, including hemoglobin. With uncontrolled blood sugar, there's more sticky stuff, and HbA1c levels go up.
101
What does A1c stand for?
A1c stands for Hemoglobin A (adult) with extra sugar groups at the 1c location.
102
What is considered a normal HbA1c level?
A normal HbA1c level is probably five or lower.
103
What is a common cause of massively high HbA1c?
Unmanaged diabetes.
104
What occupies hemoglobin in carboxyhemoglobin?
Carboxyhemoglobin is hemoglobin occupied by carbon monoxide.
105
Does the body produce carbon monoxide?
The body produces a small amount of carbon monoxide from chemical reactions.
106
What is a typical normal percentage of carboxyhemoglobin?
Typically, you might have 1% carbon monoxide occupied hemoglobin.
107
What percentage of carboxyhemoglobin might indicate an abnormal environment?
If in an abnormal environment, it probably goes up to about four percent.
108
What does a blood sample showing 4% carboxyhemoglobin indicate?
If a blood sample shows 4% carboxyhemoglobin, it had to come from some other source.
109
Describe carbonic acid and its dissociation.
Carbonic acid is a relatively weak acid that dissociates into a proton (H+) and bicarbonate (HCO3-).
110
What is bicarbonate (bicarb) in this chemical reaction?
Bicarbonate (bicarb) is the conjugate base.
111
How strong is bicarbonate relative to carbonic acid and other bases?
Bicarb is definitely not a strong base compared to others like sodium hydroxide. Bicarb is a much stronger conjugate base than CO2 is an acid. The comparisons are relative.
112
What is the actual acid being looked at in the chemical reaction involving carbonic acid?
The actual acid being looked at is the PCO2. Carbonic acid (H2CO3) is hard to measure and not much is around.
113
Why do the chemical equations involving CO2 favor movement in a certain direction in the body?
The chemical equations favor movement in that direction because there is so much CO2 around. CO2 is everywhere and has a high partial pressure. It's soluble. There's lots of CO2 in our blood.
114
How does CO2 primarily stimulate respiratory drive?
Primarily, this is via the CO2 that turns into protons, which directly activate peripheral and central chemoreceptors.
115
Rank the importance of blood gases/protons for adjusting ventilation.
Ranking: Protons (from CO2) are number 1, CO2 itself is number 2, and Oxygen is probably the third most important.
116
When do peripheral O2 sensors typically start activating significantly?
Peripheral O2 sensors really don't fire crazily until PAO2 is relatively low, around 76 mmHg. That's the ballpark number for when they start activating.
117
How does chronic high CO2 and protons affect respiratory drive in emphysema patients?
If protons remain chronically high, the tertiary gas sensor system (O2 sensors) kicks in. Patients become almost entirely dependent on respiratory drive stimulated by oxygen levels. They switch from looking at CO2 and protons to being almost entirely reliant on O2 levels to adjust ventilation.
118
What happens if you give 100% oxygen to a patient with chronic respiratory disease who is reliant on hypoxia sensors?
If they are totally reliant on hypoxia sensors (looking for PO2 around 70 mmHg), giving them 100% oxygen will likely cause them to stop breathing because they lose their primary drive.
119
What is the real underlying problem for such patients who stop breathing when given high oxygen?
The problem isn't really oxygenation but the increased acids they aren't blowing off.
120
What is the consequence of these patients stopping breathing?
If there's no drive because PO2 is relatively normal, acids build up in the blood, resulting in apnea. Apnea evolves into respiratory acidosis, even worse than the current situation.
121
What is the estimated total surface area of the alveoli in the lungs?
The total surface area basically averages the size of a tennis court.
122
How much oxygen do we need to extract per minute from the environment?
We need a lot of surface area to extract 250 cc (a little less than a can of soda) of oxygen per minute from the environment. The only way to do it is with lots of surface area.
123
Are all pulmonary capillaries or alveoli always being used?
Not all pulmonary capillaries or alveoli are always being used.
124
What does the body limit regarding ventilation?
The body limits dead space ventilation.
125
If there is no dead space ventilation, what can be said about unused alveoli?
If there's no dead space ventilation, unused alveoli must not have blood flow or air flow. This means many alveoli are not in service at any given time.
126
What is a possible reason for keeping many alveoli in reserve?
Safety factor or defense mechanism.
127
How does keeping alveoli in reserve help when exposed to toxins?
If exposed to toxins, limiting exposure to a portion of the lung limits the damage. It's probably best not to have the entire lung exposed to poisons or inhaled substances if the situation is temporary.
128
What does Dr. Schmidt typically think of when considering a sigh noise?
When Dr. Schmidt thinks of a sigh, they think of the noise someone makes, like 'Man, that was crap'.
129
How often does an adult typically sigh?
An adult typically sighs about 12 to 15 times per hour.
130
Is sighing usually a conscious action?
This is not because they feel down but because it's built into the control centers. We do this about a dozen times per hour, usually without noticing.
131
What happens just before a sigh?
To have a sigh, a deeper breath was taken just before. This deeper breath provides the extra volume that is then let out as the sigh.
132
How is sighing applied on a ventilator?
Sighing is an option on the ventilator to apply occasionally. It usually just ups the inspiratory pressure a bit, putting more air in the lungs, then goes back to normal. On old ventilators, it might just be a button to insert one sigh into the settings.
133
What is a likely purpose or benefit of occasional sighing?
This is probably useful for maintaining patency of most alveoli. An occasional deep breath would likely be useful in making sure surfactant levels in the lungs are as normal as possible. It helps make sure there aren't big collapse areas. Keeping them active every now and then is good for lungs ventilated for a long time.
134
How might changing lung volumes periodically (like sighing) help with surfactant?
Changing lung volumes periodically (like with sighing) probably helps free up surfactant. Anything to get extra surfactant dispersed is good.
135
Can surfactant be put into a ventilator for adults?
Surfactant can't really be put into the vent for adults because it would only go to areas with open alveoli, which then you wouldn't need the surfactant. You need it to reach the places that DON'T have surfactant.
136
What breathing pattern is probably similar to sighing?
Yawning.
137
What might be a reason for taking a deep breath/yawn before laying down to sleep?
A real deep breath (yawn) might be smart before laying on your back to go to sleep. When on our back (supine), lung volume decreases. Functional Residual Capacity (FRC) goes from about 3 liters to about 2 liters when lying down. That's a move of about a liter. If operating at very low lung volumes for 8 hours of sleep, taking a deep breath/yawn before laying down likely prepares the lung for low lung volumes.
138
What can influence respiratory control besides basic reflexes?
Higher order systems can influence what's happening with respiratory control.
139
What area in the brain was mentioned as having modulation of the respiratory system?
Areas higher up, like the lower part of the pons, have some modulation of the respiratory system.
140
What is the pontine respiratory group, and what is its function?
The pontine respiratory group is the thing that cuts inspiration off at a normal time.
141
What type of breathing occurs without the pontine respiratory group?
Without the pontine respiratory group, there is agonal breathing.
142
Describe agonal breathing.
Agonal breathing is characterized by very long periods of inspiration followed by very short periods of expiration. Agonal breathing is very bad.
143
What kind of brain injury can lead to agonal breathing patterns?
If someone has a very bad traumatic head injury, pontine groups can get separated from control centers lower in the medulla.
144
Where is a common lesion site in severe brain injury that affects respiratory patterns?
If you have a gunshot to the head or a real bad car wreck that destroys the central nervous system, a common lesion site is right at the junction of the pons and medulla. Everything else gets separated from the medulla. This physical separation can happen with a really bad brain injury.
145
What breathing pattern results from the separation at the pons/medulla junction?
That's the type of breathing pattern you go into: agonal breathing.
146
Is agonal breathing recoverable?
It depends on the problem. If it's massive head trauma, things don't look good. If it's something more temporary, maybe it's recoverable.
147
What anatomical junction is important in maintaining normal respiratory patterns?
The pontine-medullary junction is important in maintaining normal respiratory patterns.
