Nutrition red blood cells Flashcards
Why RBCs need to be flexible and how they achieve it
The shape, because no nucleus, no mitochondria, there is actin inside the cell that keeps it in this form
Biconcave disk, very skinny
Increase surface area for oxygen exchange
Membrane needs to be very flexible (120 days lifespan) to squeeze in small capillarie
Composition of hemoglobin
Tetramer of proteins 2 alpha and 2 beta globin
2 heme groups
What kind of compound is heme and what structure it has
It is a special product of AAs
It is called pyrrole ring with 4 nitrogens in the center
and iron is connceted with 4 bonds with N and 2 with oxygen-> coordination muber of 6
What AAs binds Fe in hemoglobin
Histidine
Myoglobin is
Monomeric polypeptide chain with heme in thce center
Myoglobin will accept oxygen from hemoglobin in capillaries, that will provide oxygen for aerobic metabolism in muscles (generating through continuation of TCA cycle)
Third type of hemoglobin
Fetal hemoglobin ( 2 alpha and 2 beta chains)
What is oxy,deoxy,carboxy hemoglobin
Oxy-> oxygen bound to iron (bright red)
Deoxy-> no oxygen bound to iron (darker red)
Carboxy (CO bound)- cherish red, binds more strongly then oxygen
What minimum hemoglobin should be bound to oxygen and with what equipment
Pulseoxymeter (measures the difference between color of oxy and deoxy-Hb)
SPO2 95% anf higher, if below 90% ->problems breathing
What is carbamino -Hb
CO2 bound to globin part of Hb
It contributes to a quarter of CO2 transportation
Co2 is also more strongly bound to Hb than oxygen
NO is ___ and binds to
It is a vasodilator that binds to globin
Why something binds to globin, in what state is iron
Fe 2+
What is Met-Hb
Oxidized iron (brown color in raw hamburgers)
How glucose gets inside RBCs
GLUT 1- keeps the concetration is the same as in plasma (5 mmol/L)
and then it is converted quickly to G6P to capture inside glucose
In chronic hyperglycemia what happens to glucose that get inside the RBCs
Glucose+Hb-> increase of HbAc, non-enzymatic glycation
Should be 5% ( in normal people)
in diabetic from 6.5-11%
What do we need to do to keep RBCs healthy
Keep electrolytes (Na-K Atpase)
Generate ATP by glycolysis, no futher , because no mitochondria. the end is pyruvate, which is converted to lactate and send to cori cycle
NADH that is generated through glycolysis help to reduce iron
To keep the cell protected from free radicals-> glutathione. G6P dehydrogenase that takes glucose through the pathway that will generate NADPH and that will reduce GSSG to GSH
How do we control oxygen release from RBCs
We have an isomerasition of 1,3 diphosphoflycerate to 2,3, that binds with hemoglobin more and prevents release of oxygen and results in keeping HbO2 in its oxidized state
So energy state of the cell and the level of ATP that is going to influence the proportion of 1,3 and 2,3
In tissues we have more 1,3 and less 2,3 to release oxygen
How fetus its oxygen supply
Through maternal circulatory system, there is a pool of mother’s blood in placenta
Fetal hemoglobin is hungrier for oxygen (because of alittle different AA profile) than maternal hemoglobin, at any oxygen concentrations fetus is going to capture oxygen from mother
What happens with baby when he is born and does not get ocygen from mother
New hemoglobin is going to be synthesized to adult hemoglobin
A complete turnover of RBCs in 2 month+ growing-> huge requirement iron
Get in breast milk
How baby can meet the needs for iron from breast milk if milk is low in iron
in milk higher availability, because it is in the form of lactoferrin (2+ Fe)
What type of disesase is G6PD deficiency
Genetic, X-linked, recessive, many SNPs
people who are homozygous recessive
How G6PD can be bad and good
There can be some crisis, that sets up oxidative stress due to lack of glutathione
Can be infection or fava beans (prooxidant)
Higher AGE’s, hemolytic anemia, increased bilirubin, jaundice
But protection against malaria (some drugs agaisnt anemia are toxic to people with G6PD deficiency
Jaundice is a condition that causes skin and the whites of the eyes to turn yellow.
AGE’s-Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars.
Describe iron metabolism
We absorb iron as Fe 2+
Free iron is toxic, so it is always should be bound to protein
Ferritin (3+) inside the cells (enterocytes) and then on the basal lateral side we have ferroportin that escortes iron out. Iron is brought to transferrin.
Transferrin trasnports iron to the bone marrow.
In bone marrow iron (2+) is combined with protoporphyrin->heme and then it is added to already existing globular proteins.
Hb take out nucleus->RBCs for 120 days
All RBCs go to the liver to be catabolized. Heme is converted to bilirubin
What happens to iron metabolism when we become iron deficient
We use iron stores (ferritin)
- Depletion of iron stores
– decreased plasma ferritin - Changes in iron transport
– increased absorption efficiency
– increased transferrin iron binding capacity
– decreased transferrin saturation %
– increased transferrin receptors - Defective erythropoiesis
decreased plasma iron
Erythrocyte protoporphyrin - Iron Deficiency Anemia
Microcytic hypochromic erythrocytes
Associated behavioural signs
Iron is bound to protein in what form
Fe 3+ and it functions as Fe 2+
What acute phase protein is trasnferrin
Positive
Why when we have an infection or cold transferrin increases?
It keeps iron from invading pathogens, because they need iron to replicate, so we sequesture all iron in proteins
The other case when we have increased concentration of trasnferrin (not infection)
Iron deficiency, because we have 6 binding sites on trasnferrin and to be more efficient in absorbing iron, we make more transferrin, so we can bring more iron to bone marrow
Do we have big storage of iron
No, it is actually low, most of iron is working iron in RBCs or in other proteins
Most of ferritin is stored in
Liver
Causes of iron deficiency
- Decreased dietary iron
– Less iron absorbed
– Vegetarian diets lack heme - Inhibition of absorption
Mineral Interactions: Calcium, zinc
supplements can iron absorption
Absorption inhibitors
If iron is in 3+-> not absorbed
3. Increased red cell mass
Pregnancy, growth
4. Increased losses
hemolysis
GI bleeding (occult)
Heavy menstrual losses
How vitamin E can be related to hemolysis
It is antioxidant, that is fat-soluble, keeps integrity of cell membranes
How heme iron is absorbed and released
Heme Iron
• 25% absorbed
• Absorbed as heme
• Fe released in
mucosal cell
What to do if diagnosed with iron deficiency
Take iron and then retest ( did dietary iron made a difference), if not than looking for problem in absorption or increased losses
Absorption of non-heme iron
Absorption highly
variable: 1‐50%
absorbed, average <10%
– Released from ligands
by gastric HCl
– Absorbed as Fe2+
reduced ferrous iron not
as Fe3+ oxidized ferric
iron
There is one AAs that is very importnat in making Hb, its deficiency can cause low hemoglobin
Histidine
RDA for iron fo rmen and women
Men -8
Women -18
Iron deficiency anemia cut offs
Hb<140 in men, 120 mg/l in premenopause women, 140 in postmenopausal
What is hepcidin
Hepcidin is a key regulator of the entry of iron into the circulation in mammals from intestine or stores. synthesized in liver
It is master regulator of iron
Its job is to sequesture iron in these stores, so that pathogens do not have a chance to use it
IL-6 stimulates hepcidin pathway in the liver
What is the action of hepcidin
It binds to feroportin, internalizes it and targets it to be broken
So if there is less feroportin-> iron does not get out, it is still bound to ferritin, so after three days intestinal cell turnover and we do not absorb iron at all
we are deficient (it is usually decreased-> more ferroportin->more absoprtion)
Draw a cheme of iron pathway
Why it is not good idea to foritfy all products with iron
Hemochromatosis: (chronic iron overload with tissue damage)
5+ types - Autosomal recessive
Defective regulation of hepcidin synthesis (decreased)
Increased ferroportin synthesis
Very efficient iron absorption
Iron deposition as hemosiderin, –cirrhosis
Men will at risk more,because they has less losses
What is the response of the organism to decreased oxygen supply
Secretion of erythropoietin, a hormone that stimulates the bone marrow to produce more RBCs
Stages of RBC developmentProery
Proerythroblast in bone marrow
Erythroblast
Then early intermediate phase,where DNA decreases, nucleus extruded,mitochondria disappear
Reticulocytes->blood->mature erythrocytes
How erythropoietin secretion is stopped
Negative feedback to kidneys, when increased O2 supply
How atheletes can play around with erythropoietin
They can train in high altitutes, so increased RBCs count
Nee to come to olympics ahead of time
If you can take exogenous erythropoietin, you can have increased endurance
Or to sleepin low oxygen environment
What is one unit of heme made of and how it is made
Aminolevulinate subunits are connected together
Succinyl CoA(from TCA cycle)+ Glycine-> (with ALA synthease) to aminolevulinate
Then PBG sythase connects Aminoevulinate into porphobinogen
PBG deaminase connects 4 of this units into the chain and they are connected in cyclic form
Decarboxylase finish the formation of heme, so nitrogens are getting ready to accept iron
Ferrochelase puts iron onto heme, finishing the reaction
What is acute intermittent porphyria
decrease synthesis of PBG deaminase, the problem is that there is an increasse in precursors but decrease in heme.
Usually heme will stop the sysnthesis reaction by negative feedback, so more ALA. It is toxic to neurons and produce psychiatric problems
Treatment of AIP is high CHO diet, it will decrease the production of precursors or get some heme precursors that will result in negative feedback, in very bad cases glucose through IV
What is porphyria cutanea tarda
decarboxylase is blocked, results inchanges in the skin when it is exposed to sunlight, in may increase hair growth, blistering and darkening in the skin. The therapy is to stay out of the sun
Sickle cell anemia is the result of
SNP (autosomal recessive)
Glutamic acid is changed to Valine
Sickle cell anemia ressembles G6PD deficiency how
Homozygous- not good
heterozygous- protection against malaria
Lactose persistent also a survival mechanism
Difference between homozygotes and heterozygotes sickle cell anemia
• Homozygotes
– Hb polymerizes under
low oxygen tension
– RBCs sickle, get stuck,
ischemia
• Heterozygotes
– Resistant to malaria
Heme is degraded where and how
In the liver
Protein is broken down thorugh proteolysis
Heme is degraded firstly by breakig the cyclic structure into the chain (biliverdin) and then we convert it to bilirubin
Who we exrete bilirubin if it is not soluble
Conjugated. In the liver, bilirubin is conjugated with glucuronic acid by the enzyme glucuronyltransferase, making it soluble in water: the conjugated version is the main form of bilirubin present in the “direct” bilirubin fraction. Much of it goes into the bile and thus out into the small intestine.
Some of it is excreted through bile, which is going to be converted to stercobilinogen by bacteria (color of feces).
Or bilirubin diglyconuride (conjugated type) can go to kidneys and be excreted through urobilinogens
What is jaundice
Another term is (icterus)
Accumulation of biliruin in different tissues
The result of increased need to degrade heme , when increased RBCs degradation, hemolytic anemia, like in malaria, also when there is liver disease
Or Liver can be fine, but there is a problme in removing of bilirubin, the problem in bile duct (cholestasis, bilary atresia)->pale feces, dark urine
How neonates can have jaundice
Babies can have not such developed liver function or not be able to produce bilirubin or to get read of it
Babies can have lighter feces because they do not have bacteria yet, not mature liver
Can make an exposure to UV light to help break bilirubin
