November 8, 2023 Flashcards
Given the following:
➢{Hb} is 14g/100mls blood
➢Arterial blood Hb is 90% saturated based on the arterial PO2
➢Venous blood Hb is 60% saturated at the resting venous PO2
Calculate the (a-v) O2 difference
Aterial:
1.34(0.9) = 1.206mls O2/g Hb
14g Hb/100mls x 1.206mls O2/g Hb
= 16.884 vols%
Venous:
1.34(0.6) = 0.804mls O2/g Hb
14g Hb/100mls x 0.804mls O2/g Hb
= 11.256 vols%
(a-v)O2 difference:
16.884 - 11.256
= 5.63 vols%
Use words to describe why a superbly trained athlete can experience hypoxemia during intense exercise
ANSWER QUESTIONS AT BEGINNING OF EACH LECTURE
what is the response of the kidney and bone marrow to reduced O2 delivery?
increase EPO secretion and RBC production
how does the kidney and bone marrow negative feedback loop work when there is reduced tissue O2 delivery
- reduced O2 carrying capacity
- kidney secretes Erythropoietin (EPO)
- EPO stimulates bone marrow to produce RBCs
- Increased O2 carrying capacity
How does EPO affect stem cells
- EPO stimulates the differentiation of stem cells into erythroblasts and further into erythrocytes
- Precursors that lead to RBCs
3.Proliferation of erythroblasts
4.Maturation (enucleation) of reticulocytes into the RBC (removal of nucleus)
page 116
what is Aplastic Anemia and how does it occur
Occurs when the bone marrow is destroyed by radiation or chemicals (insecticides, herbicides, organic solvents, paint removers, and other toxic chemicals); since RBCs are made in bone marrow you will become anemic
how is Aplastic Anemia treated
requires a bone marrow transplant
in what scenario is Aplastic Anemia done on purpose
Sometimes done on purpose, as with chemotherapy to treat blood cancers(i.e. lymphomas); destroy stem cells, then replace it
how are anemias characterized?
low Hct and Hb
Impaired endurance performance (fatigue)
how is Aplastic anemia induced:
chemically induced
how is Sickle cell anemia induced:
genetically induced
how is Pernicious anemia induced:
surgically or diet induced
how is Iron-deficiency anemia induced:
diet induced
(meat and fish are important sources of Fe; the redder the meat or fish, the more iron)
what are the results of 2 weeks of iron deficiency:
➢VO2 Max
➢Hematocrit
➢Mitochondrial enzymes
➢Endurance
➢VO2 max decreases about 50%
➢ Hematocrit decreases 60% (100 to 40)
➢ Mitochondrial enzymes decrease about 80% (100 to 20)
➢ Endurance totally diminishes
graph on page 118
what are the results of Dietary iron repletion over 7 days after having 2 weeks of iron deficiency:
➢VO2 Max
➢Hematocrit
➢Mitochondrial enzymes
➢Endurance
➢VO2 max is closely related to O2 transport capacity (related to Hct)
➢ Mitochondrial enzymes and endurance take a few days to increase
➢ All increase to about normal within a week
how does Vitamin B12 affect RBC
Stimulates RBC synthesis
what does a lack of Vitamin B12 do
Lack of Vitamin B12 causes anemia
where can Vitamin B12 in the regular diet
found in fish, meat, yogurt, milk, etc.
what diet is deficient in Vitamin B12
It is deficient in the vegan diet
what is Pernicious Anemia
deficiency in Vitamin B12
How does Vitamin B12 lead to RBC synthesis once ingested
- Parietal cells in the stomach secrete IF (intrinsic factor)
- IF binds ingested vitamin B12 (B12 can’t be absorbed without IF)
- IF-B12 complex is absorbed by the gut by endocytosis and travels to the bone
marrow - Vit B12 stimulates RBC synthesis in bone marrow cells
what is the primary cause of Pernicious Anemia
Lack of parietal cells result in a lack of B12 being taken up (can be sufficient in diet just not being absorbed because no IF meaning not being taken up into bone
marrow)
The primary cause of pernicious anemia is a deficiency of intrinsic factor, a protein produced by the stomach lining. Intrinsic factor is necessary for the absorption of vitamin B12 in the small intestine. Without sufficient intrinsic factor, vitamin B12 cannot be effectively absorbed, leading to a B12 deficiency.
what is Sickle Cell Anemia
Sickle cell anemia: a genetic disease due to a ‘point mutation’ in the beta globin gene; it affects 0.14% of the African American population in the US
how many globin subunits are in adults Hb?
How many polypeptide chains?
In adults Hb, there are 2 alpha and 2 beta globin subunits
(4 polypeptide chains)
how many amino acid chains does the alpha globin subunit have?
How many does the beta-globin subunit have?
The alpha globin subunit has 141 amino acid chains
beta globin subunit has 146 amino acids
what is each globin subunit bound to
Each subunit is bound to heme, which contains a central iron atom which binds O2
3 nucleotides = ______ amino acids
3 nucleotides = 1 amino acids
what is a ‘point mutation’
a change in a single nucleotide base (ex: ATCG) within the DNA sequence of a gene.
How does Sickle Cell Anemia happen
a change in a single nucleotide base in the codon for glutamate results in amino acid switch in the primary structure (valine instead of glutamate)
this causes Beta globin proteins that are mutated, to polymerize(combine together) the cell at a low PO2 →
this leads to distorted RBC shape and stiff cells which plug capillaries, then break (hemolysis), and this leads to anemia
how many nucleotides in the B-globin gene are required to code for the functional protein
3x146
what subunits are expressed in fetal Hb
alpha2, gamma2
Gamma are expressed in children
what subunits are expressed in adult Hb
alpha2, beta2
Beta and alpha are expressed in adults
when Gamma gene shut off
Gamma gene is shut off postnatally
what is Hydroxyurea
- a drug that increases the production of fetal Hb by inducing gamma (y) subunit expression
- this competes with the beta subunit during Hb synthesis and ‘replaces’ it, leading to more Hb F (fetal) in the blood
Fetal Hb does not have the mutated beta globin subunit which causes sickling
Fetal Hb does not have the mutated beta globin subunit which causes sickling
does Hb F or Hb adult have stronger affinity for O2
Hb F has a stronger affinity for O2
The Function of Myoglobin (Mb)
and
How does it work
An iron containing protein which binds O2 and is found in muscle
Mb stores O2 and facilitates its diffusion within the muscle cell to the mitochondria
which has a higher O2 affinity Mb or Hb
Mb has a higher affinity for O2 than Hb does
why is Mb Important in aquatic animals
Important in aquatic animals so they can store sufficient O2 to remain underwater for long periods of time
not so much in other mammals for endurance purposes
explain the Mb “knockout” animal (mouse) experiment
removed Mb from mouse
results showed:
Heart and skeletal muscle become pale
However, endurance performance was not impaired
how is Mb useful as a diagnostic tool
It is supposed to be in muscle, and if you find it in the blood, this means it has leaked out (rhabdomyolysis) - muscle injury has taken place
Breakdown product of released myoglobin (ferrihemate) is toxic to kidney epithelial cells, and can cause acute renal failure
Because myoglobin is also found in high concentration in the heart, it is a sensitive marker for cardiac muscle injury, making it a potential marker for
heart attack in patients with chest pain
Describe some characteristics of Restrictive Lung disease (stiff lung):
compliance:
elasticity:
examples of Restrictive disease:
air inspiration/expiration:
Decreased compliance
increased elasticity
Pulmonary fibrosis, pulmonary edema
Hard to get air in, decreased volume of air per breath
Describe some characteristics of Obstructive Lung Disease (COPD):
compliance:
elasticity:
examples of obstructive disease:
air inspiration:
Tidal volume:
Increased compliance
decreased elasticity (floppy lung)
Emphysema, bronchitis (small airway, obstructive diseases, causes often related to smoking)
Asthma (large airway, obstructive disease)
Easy to get air in, difficult to get air out
Smaller tidal volume
