Plasma concentrations and RBC Metabolism Flashcards
Why don’t small embryos need cardiovascular systems?
they are small enough that diffusion is enough to get oxygen in and waste out of their entire body - but as soon as they’re bigger than a few mm, they need a CV system, which is why it’s the first to develop
the cardiovascular system is inherently linked to what other system?
lymphatics
What is the normal pH of blood?
7.35 to 7.45, averaged to 7.4 (slightly alkaline)
Describe blood’s temperature?
higher than normal body temp
What is the composition of plasma?
91% water, 7% blood proteins, 2% nutrients, hormones, electrolytes, etc.
What percentage of the whole blood is plasma?
46-63%
What are the three primary classes of plasma proteins?
albumins
globulins
fibrinogen
Where are most of the plasma proteins produced?
in the liver (about 90% of them): all albumins and fibrinogens, and most globulins
What happens in terms of plasma proteins in cirrhosis?
The liver isn’t working appropriately and fails to make enough albumin. Without the albumin, the oncotic pressure in the plasma isn’t high enough, so you don’t pull fluid back into the CV system on the venous side. This results in a buildup of fluid in the abdomen, called ascites.
What percentage of the total oncotic pressure in the plasma is from albumin?
about 70-80%
What is the function of albumin?
it’s a carrier protein for free fatty acids, calcium, zinc, steroid hormones, copper and bilirubin
What do you have to consider about albumin in terms of drug dosing?
It’s capable of binding some drugs - this both decreases their effective concentration and increases their lifetime in circulation (so if you know a drug is a binding substrate for albumin, you have to take that into consideration when taking levels)
Which direction does fluid move on the arterial end? venous end?
fluid is pushed out of the vessel on the arterial end because of starling forces (high hydrostatic pressure beats the oncotic pressure)
fluid is pushed into the vessel on the venous end because the hydrostatic static pressure is no longer high enough to overcome the constant oncotic pressure inside the vessel
What are the two general types of globulins in the plasma?
antibodies and transport globulins
What is the function of fibrinogen?
clotting - they interact to form lots insoluble strands of fibrin that make the framework for a blood clot
How can anemias be classified?
based on RBC size (normocytic, microcytic, and macrocytic) and hemoglobin concentration
What is the mean corpuscular volume?What’s normal?
the average volume of a patient’s RBC - normal is 80-100 femtoliters
What is a normal mean corpuscular hemoglobin concentration?
32-37 g/l is normochromic
under 32 is hypochromic
Why is an RBC’s shape important for function? (2 reasons)
- It allows the RBC to travel through spaces that are smaller than itself
- the large ratio of surface area to volume allows for rapid O2 absorption and release
Nutritional deficiencies in what will produce inadequate RBC production?
B12, iron, and folate
What hormone stimulates erythropoiesis? Where is is secreted from? When?
erithropoietin (EPO) from the kidneys in response to anything that will reduce O2 transport: anemia, decreased blood flow to the kidneys, O2 content of lungs declines, respiratory surfaces of the lungs are damaged, etc.
EPO accelerates the maturation of RBCs by doing what?
mainly by speeding up the rate of Hb synthesis (can increase it by 10-fold in the bone marrow)
What do you call the blast cell after it extrudes the nucleus/
a reticulocyte
Where in the body do the reticulocytes mature into RBCs?
the spleen (they lose ribosomes, mRNA and ability to divide)
What organelle DO the RBCs retain?
the cytoskeleton - for structure
What is the life span of an RBC?
120 days
How do old RBCs get removed?
any RBC that has a cell membrane rupture or other damage will be detected and engulfed by a phagocyte - mostly in the spleen, but also the liver
What is heme broken down to in the macrophages?
biliverdin first, which is then converted to bilirubin (in the spleen)
What binds bilirubin to transport to the liver? How is it excreted?
albumin binds it and takes it to the liver for excretion in the bile
What happens to the billirubin when it reaches the small intestine with the bile?
It’s converted to pigments called urobilinogens and stercobilinogens which are excreted in urine and feces
How do RBCs get their energy if they don’t have a nucleus or mitochondria? Why is this evolutionarily a good idea?
anaerobic metabolism of glucose (from the surrounding plasma)
It’s a good idea because it means that no O2 will be “stolen” by mitochondria in the cell and literally all the O2 can be saved for tissue
What happens in a RBC metabolism enzymopathy?
in general, it results in ATP-deficient RBCs that are rigid and therefore removed by the spleen
What is the most common glycolysis pathway enzympathy ?
pyruvate kinase deficiency - causes a hemolytic anemia (severity ranges)
To bind oxygen, what state does hemoglobin’s iron have to be in?
ferrous (Fe2+)
Why is oxidative stress so bad for RBCs?
ROS can oxidize Fe2+ to ferric iron (Fe3+), which cannot bind oxygen
What do we call hemoglobin if it’s iron is in the ferric state (Fe3+)?
methemoglobin
How does the body regenerate hemoglobin from methemoglobin?
It uses NADH from the NADH-cytochrome b5 methemoglobin reductase system
Describe the presentation of a patient with congential methemoglobinemia?
They look blue! But really don’t have many issues. It’s from excessive methemoglobin due to a deficiency in cytochrome b5 reductase, or just from excess methemoglobin because of a mutation that stabilizes the Fe3+ form
How can you get an acquired methemoglobinemia? What’s the treatment?
By ingesting oxidants like nitrites, quinones, aniline and sulfonamides like BENZOCAINE, lidoaine and dapsone
Treat with a reducing agent like ascorbid acid or METHYLENE BLUE
Within RBCs, there is a shunt in glycolysis to generate what O2-binding modulator?
2,3, bisphosphoglycerate (2,3-BPG)
What does 2,3-BPG do?
It stabilizes the deoxy form of hemoglobin, so it facilitates the release of O2 to the tissues (just remember that Lance Armstrong used it in the doping scandal)
What will happen if 2.3-BPG formation is defective?
Hb will not release O2 and you’ll have hypoxia and hemolysis
What is the body’s major strategy for removing ROS outside of peroxisomes?
glutathione
In what state must glutathione be in order to reduce hydrogen peroxide to water? What cofactor is necessary for this? From what pathway?
It has to be in the reduced state - the sulfhydryl form.
This requires NADPH from the pentose phosphate pathway (NADPH gets oxidized to NADP+)
What do we need in our diets to have glutathione?
selenium
What does glucose 6 phosphate dehydrogenase do?
It catalyzes the first step of the pentose phosphate pathway to form NADPH to keep glutathione in the reduced form.
What happens in G6PD deficiency?
The pentose phosphate pathway doesn’t work, so you don’t have reduced NADPH to reduce glutathione. So in the event of an oxidative stressor (eating fava beans, sulfonamide drugs, etc), the patient will have a acute severe hemolytic anemia related to oxidative damage
How can you diagnose a G6PD deficiency?
test the enzyme level at steady state
look at a peripheral blood smear and you’ll see Heinz bodies, bite cells and blister cells
What are the symptoms of a G6PD deficiency?
dark urine, pale skin, jaundice, hepatomegaly, splenomegaly, tachycardia, fever
THe amount of O2 bound to hemoglobin depends primarily on what?
the O2 content of the plasma: low plasma O2 - Hb will release oxygen
Describe what happens to O2 binding when pH decreases (H+ concentration increases)
the CO2 produced by metabolism is converted to carbonic acid in the RBCs. This dissociateds into bicarb and a proton.
THe proton reacts with the Hb int eh RBC, which causes comfortmation changes such that O2 is released into the tissue
Describe what happens to O2 binding when pH increases - in the lungs for example?
Here, carbonic anhydrase can cleave carbonic acid into H20 and Co2, and the Co2 is exhaled
Less Co2 means H+ binding to Hb
O2 is then free to bind to Hb to be carried to the tissues
Although most of the CO2 from metabolism is carried to the lungs as bicarb, some binds to Hb. What form of Hb does htis stabilize?
this stabilizes the deoxy conformation, so O2 is more likely to be released to the tissues during times of high CO2 concentration, which just makes intuitive sense
What effect will increased temperature have on O2 binding to Hb?
Increased temperature denatures the O2-Fe bond such that is reduces the affinity of hemoglobin for oxygen, thus facilitating release of O2 for the tissue (reduced temperature has the opposite effect)
How can the spleen tell when an RBC has gone bad?
the passageway thorugh the spleen is only 3 microns ind iabmeter and the RBC is over twice that size. THis means that it has to deform itself in order to pass through. If it’s damaged and can no longer deform, the RBC will become stuck and macrophages will know to come break it down
What happens in hereditary spherocytosis?
Sometimes wrong with one of the RBC’s membrane proteins - usually ankyrin
- this means you have aberrant interactions between the lipid bilayer and the cytoskeleton, such that the RBCs have reduce deformability and the spleen removes them at much faster rates, causing an anemia
When can hereditary spherocytosis present?
You would think just in neonates (and that’s when it presents most often), but it can present in all ages
Often it will come on with any illness that causes splenic hypertrophy, like mononucleosis
What is the gold standard test for diagnosing hereditary spherocytosis?
you do an incubated osmotic fragility test - it measures the ability of the RBCs to swell in a graded series of hypotonic solutions
What is the main treatment for hereditary spherocytosis?
splenectomy - it corrects the anemia, but not the RBC defect obviously.
