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Breathing Problem

Last summer at a farm in Mohawk, New York, a 39 year old farm hand was overcome while climbing up the chute of a recently filled silo and was taken to the emergency room. In the preceding 10 days, the farm owner had filled this silo with grass and chopped corn silage. On the day of the farmhand’s illness, the harmer had asked him to climb up the unloading chute inside the silo and toss out fresh silage. When the farmhand climbed the chute, he became short of breath and confused and had to descend. No obvious cause for his trouble (no excessive heat, strange odors, etc.) was noted, so he made a second attempt but again had to climb down and was noted to be cyanotic, pale, and diaphoretic.

Question 1 - Single Best Answer

Cyanotic and diaphoretic mean?

A) Blue and sweaty.
B) Yellow and hot.
C) Blue and gasping for breath.
D) Gasping for air and bleeding from both nostrils.

Question 2 - Single Best Answer

The significance of cyanosis is?   

A) He had a fever.
B) He was having an allergic reaction.
C) He wasn't getting enough oxygen.
D) He was hemorrhaging.

Question 3 - Single Best Answer

The significance of his sweating, in the absence of excessive environmental heat, is?   

A) he had a fever.
B) he had an infection.
C) he was going into shock.
D) he had just returned from a heavy exercise session.

At a local hospital, the examining physician noted cyanosis and respiratory distress; blood pressure of 84/60; pulse, 128; respiration, 32; and temperature, 37.5 C. Normal Lab Values

The patient had wheezes and crackles on auscultation of his chest, but no signs of consolidation; after asthma was diagnosed, he was treated with epinephrine, intravenous aminophylline, and steroids.

Question 4 - Single Best Answer

What do you think led to the diagnosis of asthma?   

A) the acute onset.
B) the lack of fever
C) the wheezes and crackles
D) lack of consolidation
E) more than one of the above

White blood count was 21,000; hematocrit, 57.8%; and hemoglobin, 18.6 gm. Arterial blood gas examination while on 2 liters/min of nasal oxygen showed pH 7.35; PaCO2, 32mm Hg; PaO 45 mm Hg. An electrocardiogram showed a sinus tachycardia, and a plain chest radiograph disclosed extensive fluffy bilateral infiltrates.Normal Lab Values

Question 5 - Single Best Answer

The white cell count was?   

A) normal
B) high
C) low

Question 6 - Single Best Answer

The hematocrit and hemoglobin were?   

A) normal
B) high
C) low

Question 7 - Single Best Answer

Taken together, these two results, white count and hematocrit, show?   

A) a hemorrhage was occurring
B) the patient's volume of blood was contracted, leading to a concentration of both red and white cells.
C) the patient had an infection.
D) anemia

Question 8 - Single Best Answer

The blood gases were?   

A) Normal
B) PaCO2 was low and PaO was high
C) PaO was low and PaCO2 was high
D) Both were high
E) Both were low

Question 9 - Single Best Answer

The electrocardiogram (sinus tachycardia) and chest x-ray (fluffy bilateral infiltrates) showed?   

A) a heart attack due to a ruptured blood vessel in the lung.
B) a rapid heart beat likely due to fluid in the lungs.
C) signs pathognomonic of tuberculosis.
D) a tension pneumothorax.

Question 10 - Single Best Answer

The patient's respiratory distress and dangerously low blood oxygen concentration were due to?   

A) constricted bronchioles
B) a hemorrhage in the lungs resulting in a fluid build up.
C) fluid filled lungs
D) a pseudomembrane in the trachea
E) carbon monoxide poisoning

Question 11 - Single Best Answer

The fluid filling the lungs was?   

A) whole blood
B) blood plasma
C) water due to hydroscopic bacteria
D) CSF
E) pus

The patient was moved to the intensive care unit, where a tentative diagnosis of pneumonia was made. He became agitated, would not wear an oxygen mask, and remained in shock. Five hours after admission, he experienced cardiopulmonary arrest and died despite vigorous attempts to resuscitate him.

Post mortem examination the next day showed grossly edematous lungs with pleural effusions (200ml) on both sides; the right lung weighed 900 gm, and the left weighed 1,000 gm (normal is around 600 gm). Microscopy of the lungs showed alveoli flooded with proteinaceous material; the alveolar walls were intact. No bacteria, fungi, or evidence of viral disease was found. Early bronchiolitis (inflammation of the bronchioles) was present. There were no granulomas or hyaline membranes. No hyperplasia of bronchiole musculature was seen. An investigation of the farm two weeks later failed to uncover any problem with the corn silage, which was still being unloaded. The cows were eating normally and producing the usual amounts of milk. The farmer reported that, following his farmhand's illness, he had turned on the silo blower and sent another worker up to toss out corn; no ill effects had occurred.

Question 12 - Single Best Answer

Possible causes of the patient's death include?   

A) an acute asthma attack
B) severe pneumonia
C) chemical damage to the lung
D) spontaneous pneumothorax

Question 13 - Single Best Answer

This chemical damage was likely due to?   

A) exposure to an anaerobic environment
B) exposure to carbon monoxide
C) exposure to nitrogen oxides from bacterial energy production
D) exposure to radioactive gas
E) exposure to carbon dioxide

The case outlined above is typical for massive exposure to nitrogen oxides. Silo filler's disease represents and occupational hazard associated with ensiled crops. Laboratory studies have shown that toxic levels of NO, NO2, and N2O4 are regularly produced in silos. Because these oxides are dense, they tend to settle in the chute and around the base of the silo, and exposure often occurs without the knowledge of the worker entering the silo. Although NO2 is brown and has an odor, N2O4 is colorless, and exposure can occur without warning. If undetected by smell or sight, the potent nitrogen oxides may be inhaled deep into the lungs, where contact with the mucosal moisture produces nitric acid, which burns the airways, respiratory bronchioles, and alveoli. In fatal exposure, vascular collapse and the outpouring of serum rapidly produce shock and death.

The patient died as a result of nitrogen oxide production by anaerobic bacteria in the silage. Bacteria produce these gases, instead of CO2, as a result of their energy production. This accident could have been easily prevented by ventilation for 20 minutes before the worker entered the silo or he could have been equipped with a full-face mask and an air supply.

The patient in this case died as a result of a normal bacterial process - energy production – coupled with ignorance of this possibility on the part of the farmer and the worker. Although it is tempting to see the bacteria as “them vs us” it is more often than not that the bacterial processes that are harmful to humans are just a result of the bacteria’s normal living strategy.

This case is designed to teach you about bacterial energy production. The following exercise will familiarize you with bacterial energy production, and is more important than the particulars of nitrogen oxide poisoning.

Question 14 - Single Best Answer

All life requires energy. Bacteria are no exception. For one thing, they need to synthesize macromolecules. What are other energy requiring functions?   

A) catabolism of large molecules
B) active transport
C) motility
D) anabolism of large molecules
E) B,C,D

Question 15 - Single Best Answer

How do bacteria convert the C-C bond energy in glucose to a usable form?   

A) oxidation reactions
B) reduction reactions
C) phosphorylation
D) polymerization

Question 16 - Single Best Answer

What is the most common biological hydrogen acceptor?   

A) DNA
B) cytochrome C
C) cytochrome A1
D) NAD
E) ADP

Question 17 - Single Best Answer

How is a supply of NAD assured?   

A) depolymerization
B) de novo synthesis of NAD
C) export of NADH2
D) fermentation and respiration
E) sunlight

The supply of NAD is maintained by regeneration of NAD from NADH2 – by oxidizing the NADH2. Remember that when something is oxidized something else must be reduced. Fermentation and respiration are the ways this is done. In fermentation an organic compound is reduced and NADH2 is oxidized. In respiration oxygen (or another inorganic compound like NO3-!) is reduced and NADH2 is oxidized…if oxygen is reduced it is said that oxygen is the terminal electron acceptor.

The simplest FERMENTATION reaction is the LACTIC ACID FERMENTATION. In this fermentation, pyruvic acid (produced during glycolysis) is reduced to lactic acid while NADH2 is oxidized. Pyruvate is, in fact, central to most fermentation reactions, but lactic acid is not the only product. Alcohol, acetic acid, formic acid, butanediol, butyric acid and propionic acid are all possible products depending on the attendant enzymatic reactions. Many bacteria are identified by the fermentation products they produce. NOTE that in all these reactions, oxygen is unnecessary, as an organic compound is reduced while NADH2 is oxidized.

Respiration involves electron transport in the cytoplasmic membrane and extrusion of protons (H ions) to create a proton gradient, proton motive force (PMF), or ENERGIZED membrane. The process is called aerobic respiration if oxygen is the terminal electron acceptor and anaerobic respiration if another inorganic compound is the terminal electron acceptor. In the case of the Silo-Filler, nitrate (NO3-) was the electron acceptor. A silo is a perfect environment for the production of NO2. Grass is ensiled to exclude oxygen and allow the production of acids (from fermentation) which act as preservatives for the grass and provides feed for livestock over the winter (think of a silo as a huge vat of sauerkraut). But some facultative anaerobes such as E. coli can also carry out anaerobic respiration by using NO3- as the terminal electron acceptor (in place of O2) and production NO and NO2. This allows the efficiency of respiration to be maintained and an energized membrane to be directly produced.

Question 18 - Single Best Answer

The term protonmotive force (also called an "energized membrane") means there is an electrical potential across the membrane. This electrical potential can be created when?   

A) there is unequal distribution of ATP, a potential source of energy
B) there is a higher concentration of H+ on the inside of the cell than on the outside.
C) there is a higher concentration of H+ on the outside of the cell than on the inside.
D) both A and C are correct.

Question 19 - Single Best Answer

Three functions directly energized by the protonmotive force are?   

A) Transport of sodium into the cell, transport of lactose out of the cell, and producing ATP.
B) Sodium, lactose, and calcium export.
C) Transport of lactose into the cell, transport of calcium out of the cell, producing ATP.
D) Sodium, lactose, and calcium import.
E) None of the above are correct.

Thus ATP can be used to produce a protonmotive force, and the protonmotive force can be used to produce ATP, and either fermentation or respiration can provide fuel for all the cell's energy needs, although respiration is by far the most efficient.

These steps are the final steps of bacterial energy production. The first steps involve getting nutrients into the cell. Most bacteria have envelopes to exclude harmful substances so have had to evolve ways to selectively TRANSPORT molecules that they need through these envelopes. Very few substances enter cells by simple diffusion, although water, O2, and CO2 do. Some molecules, glycerol is an example, enter by facilitated diffusion, where there is a carrier in the cell envelope that moves the substance with the concentration gradient. Substances that move against a concentration gradient require active transport, an energy requiring process. The energy can come from either ATP or an energized membrane (proton motive force) or even PEP. Lactose is transported by the lactose permease (remember the lactose operon, z, y, a, where y is the permease?). It uses energy from the proton gradient (energized membrane). Galactose is transported by breaking down ATP. In group translocation, sugars are phosphorylated by a phosphoenolpyruvate (PEP) dependent phosphotransferase system (PTS). Some sugars transported this way include glucose, mannose, and N-acetylglucosamine. The phosphate group is transferred from PEP through a series of intermediary proteins to the sugar. The protein that directly phosphorylates the sugar is Enzyme II and is sugar-specific. It is phosphorylated by HPr-P (phosphorylated HPr). One of the proteins (EII for glucose), when phosphorylated, also activates adenyl cyclase. Thus when lots of glucose is coming into the cell, cAMP concentration is low because the EII-P is being used to get the glucose into the cell so adenyl cyclase is not activated. This can lead to repression of some other transport systems (i.e., lactose) and means that if both glucose and lactose are available to the bacteria, it will use the glucose first. This is the most efficient way it can get its energy.

Question 20 - Single Best Answer

There is a higher concentration of Na+ outside cells than inside. To get Na+ OUT of the cell which process COULD be used?

A) diffusion
B) facilitated diffusion
C) active transport
D) group translocation