Chapter 49 - Hypoxia and Cyanosis

Question 1

Explain the Pasteur effect when a cell is in a hypoxic state.

Answer 1

Shift from oxidative phophorylation (aerobic metabolism) to anaerobic glycolisis.

Question 2

Name a mechanism responsible for cell death due to severe hypoxia.

Answer 2

“In seve hypoxia, when ATP production is inadequate to meet the energy requirements of ionic and osmotic equilibrium, cell membrane depolarization leads to uncontrolled Ca2+ influx and activation of Ca2+-dependent phopholipases and proteases. These events, in turn, cause cell swelling, activation of apoptotic pathways and, ultimately, cell death.”

Question 3

How might a cell adapt to hypoxia?

Answer 3

Hypoxia leads to transcription of genes that encode for proteins fundamental for adaptation. These include “glycolytic enzymes, such as phophoglycerate kinase and phophofructokinase, as well as the glucose transportes Glut-1 and Glut-2; and by growth factors, such as vascular endothelial growth factor (VEGF) and erythropoietin, which enchance erythrocyte production. The hpoxia-induced increase in expressoin of these key proteins is governed by the hypoxia-sensitive transcription factor, hypoxia-inducible factor-1 (HIF-1).”

Question 4

How do you explain that hypoxia results in vasodilation of peripheral arterioles but results in vasoconstriction of pulmonary vasculature?

Answer 4

“During hypoxia, systemia arterioles dilate, at least in part, by the opening of K ATP channels in vascular smooth-muscle cells due to the hypoxia-induced reduction in ATP concentration. By contrast, in pulmonary vascular smooth-muscle cells, inhibition of K+ channels causes depolarization which, in turn, activates voltage-gated CA2+ channels raising the cytosolic [Ca2+] and causing smooth-muscle cell contraction.”

Question 5

What are the mechanisms reponsible for headaches in high-altitude?

Answer 5

The most common is due to hypoxia induced cerebral vasodilation. On the other hand, rarely one can develop high-altitude cerebral edema, which manifests by severe headache and papilledema and can cause coma.

Question 6

Capilary leakage might be responsible for pulmonary and cerebral edema in high-altitude as a consequence of hypoxia.
True or False?

Answer 6

True.

Question 7

How do you expect to find the dissociation curve of hemoglobin-O2 in the following cases: (i) severe pulmonary disease; (ii) high-altitude.

Answer 7

(i) shift to the right

(ii) shift to the left

Question 8

Name the three groups of pathophysiological mechanisms that lead to respiratory hypoxia.

Answer 8

Ventilasion-Perfusion mismatch, hypoventilation and shunting.

Question 9

Name two causes of respiratory hypoxia that are only partially corrected with FiO2 of 100%.

Answer 9

Perfusion of nonventilated portions of the lung, such as in atelectasis, and intrapulmonary shunting, such as in arteriovenous malformations.
(right-to-left shuting, either located in the lungs or the heart, is not able to restaure PaO2 with FiO2 of 100%)

Question 10

What is the approximately altitude that result in cease of normal activity of unacclimated individuals?

Answer 10

5000m

Question 11

In anemic hypoxia, PaO2 is reduced.

True or False?

Answer 11

False.
“Although the PaO2 is normal in anemic hypoxia, the absolute quantity of O2 transported per unit volume of blood is diminished.”

Question 12

What conditions associated with hypoxia might have normal PaO2?

Answer 12

Anemic hypoxia and circulatory hypoxia.

Question 13

Name the causes of specific organ hypoxia.

Answer 13

Decrease of arterial inflow, venous congestion, reduced cardiac output and peripheral vasoconstriction due to heart failure or hypovolemic shock, for example.

Question 14

How come a healthy individual can adapt to exercise?

Answer 14

“Exercice is a classic example of increased tissue O2 requirements. These increased demands are normally met by several mechanisms operating simultaneously: (1) increase in the cardiac output and ventilation and, thus, O2 delivery to the tissues; (2) a preferential shift in blood flow to the exercising muscles by changing vascular resistances in the circulatory beds of exercising tissues, directly and/or reflexively; (3) an incrase in O2 extraction from the delivered blood and a widening of the arteriovenous O2 difference; and (4) a reduction in the pH of the tissues and capillary blood, shifting the Hb-O2 curve to the right, and unloading more O2 from hemoglobin. If the capacity of these mechanisms is exceeded, then hypoxia, especially of the exercising muscles, will result.”

Question 15

How do you expect do find pO2 in venous blood of a patient with cyanide intoxications?

Answer 15

pO2 is usually high since in histotoxic hypoxia the tissues cannot uptake O2.

Question 16

Where would one find the chemosensitive cells to hypoxia?

Answer 16

Carotid and Aortic Bodies, aswell as in the respiratory center in the brainstem.

Question 17

Which alterations in pO2 and pCO2 result in increased O2 delivery to the brain?

Answer 17

Decreasing in pO2 and increasing in pCO2.
Hyperventilation might result in decrased in pCO2, which increases cerebrovascular resistance, thus diminishing O2 delivery to the brain.

Question 18

Describe the chronic mountain sickness.

Answer 18

“In persons with chronic hypoxemia secondary to prolonged residence at a high altitude (>13,000ft., 4200m), a condition termed chronic mountain sickness develops. This disorder is characterized by a blunted respiratory drive, reduced ventilation, erythrocytosis, cyanosis, weakness, right ventricular enlargement secondary to pulmonary hypertension, and even stupor.”

Question 19

Cyanosis is due to carboxy-hemoglobin.

True or False?

Answer 19

False.
Cyanosis is due to deoxygenated hemoglobin or deoxy-hemoglobin or hemoglobin derivatives (methemoglobin or sulfhemoglobin).
“A cherry-colored flush, rather than cyanosis, is caused by COHb.”

Question 20

Where would you look for early cyanosis, especially in dark-skinned persons?

Answer 20

“mucous membranes in the oral cavity and the conjunctivae rather than examination of the skin is more helpful in the detection of cyanosis.”

Question 21

In which of the following patients do you expect to observe cyanosis for a higher value of SatO2: patient A, with severe anemia; patient B, healthy otherwise; patient C, with marked polycithemia.

Answer 21

Patient C. Note that cyanosis is a result of the absolute quantity of hemoglobin reduced in the venous territory. Therefore, in a patient with increased hemoglobin concentration, it is expected that the relative quantity deoxygenated to produce cyanosis is lower than a healthy patient (B) or one with anemia.

Question 22

Name one condition associated with central and peripheral cyanosis.

Answer 22

Cardiogenic shock with pulmonary edema.

Question 23

The presence of cyanosis and clubbing of the digits is pathognomonic of cardiac disease.
True or False?

Answer 23

False.
Although more common in cardiac conditions with right-to-left shunting, it can also be observed occasionnaly in patients with pulmonary disease, such as lung abcess or pulmonary arteriovenous fistulae.

Question 24

Cyanosis due to respiratory cause only occurs in the acutelly ill.
True or False?

Answer 24

False.

Question 25

High-altitude might cause hypoxia and cyanosis. As one is ascending, which of those do you expect to encounter first?

Answer 25

PaO2 = ~60mmHg at 3000m altitude but hypoxemic symptoms are evident at 5000m. Cyanosis might develop at 4000m. Thus, analytical hypoxemia occurs first, but symptomatic hypoxemia might occur after cyanosis, in otherwise healthy individuals at least.

Question 26

What is the mechanism that might explain reduced SaO2 in cirrhosis?

Answer 26

“SaO2 and cyanosis may also occur in some patients with cirrhosis, presumably as a consequence of pulmonary arteriovenous fistulae or portal vein-pulmonary vein anastomoses.”

Question 27

Raynaud’s phenomenon is always associated with cyanosis.

True or False?

Answer 27

False.

Question 28

List the causes of clubbing.

Answer 28

“Clubbing may be hereditary, idiopathic, or acquired and associated with a variety of disorders, including cyanotic congenital heart disease, infective endocarditis, and a variety of pulmonary conditions (among them primary and metastatic lung cancer, bronchiectasis, asbestosis, sarcoidosis, lung abcess, cystic fibrosis, tuberculosis, and mesothelioma), as well as with some gastrointestinal diseases (including inflammatory bowell disease and hepatic cirrhosis). In some instances, it is occupational, e.g., in jackhammer operators.”

Question 29

Hypertrophic osteoartrhopathy is usual with chronic cardiac disease.
True or False?

Answer 29

False.
“Clubbing in patients with primary and metastatic lung cancer, mesothelioma, bronchiectasis, or hepatic cirrhosis may be associated with hypertrophic osteoarthropathy.”

Question 30

Name one example wheares clubbing might be reversible.

Answer 30

Following lung transplation for cystic fibrosis.