wk 11, lec 2

Question 1

what are red blood cells aka

Answer 1

erythrocytes

Question 2

what do RBCs contain

Answer 2

• Carry O2
• Contain hemoglobin  bind O2 in lungs and release in tissues (for gas transport and exchange)
• Remove CO2 (bring back to lungs for exhalation)

Question 3

where are RBCs made

Answer 3

• Made in bone marrow
  o Erythron= proliferating marrow erythroid precursors + circulating RBCs

Question 4

RBC lifecycle

Answer 4

120 days

Question 5

where are RBC recycled

where are made in fetus

Answer 5

• Recycled in liver and spleen
  o Made in spleen and liver in fetus

Question 6

shape of RBC

Answer 6

• Biconcave shape; maximize SA for gas exchange and to move through vessels

Question 7

when will hemoglobin bind and dissociate at low and high [ ]

Answer 7

o Hemoglobin binds oxygen at high [ ]
o Oxygen dissociates from Hb at low [ ]
o Healthy O2 saturation in Hb is 95-99%

Question 8

when will Hb bind Co2

Answer 8

o HB binds CO2 with low affinity

Question 9

what do RBCs have to convert CO2 in bicarbonate HCO3-

Answer 9

carbonic anhydrase

Question 10

what do RBC lack

Answer 10

nuclei

o Cant synthesize protein and limit lifespan

Question 11

what are RBC derived from

Answer 11

from myeloid progenitor (pronormoblast)

Question 12

steps to form RBC

Answer 12

• RBCs derived from myeloid progenitor (pronormoblast)
  o Stimulated to divide by GM-CSF and erythropotein (EPO)
  o Before nucleus extruded; RBC accumulate Hb and proteins
  o The late normoblast because anucleate
  o Reticulocyte has remnants of golgi, ER, ribosomes which get extruded to become mature RBC

Question 13

what 2 things stimulate myeloid progensit to divide and get closer to being RBC

Answer 13

GM-CSF and erythropoietin (EPO)

Question 14

how many times does pronormoblast divide to make RBC and via stimulation of what

Answer 14

• Pronormoblast divides to make 16-32 mature RBCs via EPO stimulation

Question 15

where is EPO erythropoietin made

Answer 15

kidneys by epithelial cells

Question 16

• EPO made in kidney by epithelial cells ; what happens in high vs low oxygen conditions

Answer 16

o High oxygen conditions= hypoxia inducible factor (HIF) is ubiquinated and degraded by proteasomes

o Low oxygen conditions= HIF binds proteins, is translocated to the nucleus and stimulates EPO production (make more RBCs)

Question 17

high or low oxygen to make EPO

Answer 17

low oxygen

Question 18

generation of RBC depends on

Answer 18

EPO, bone marrow, adequate iron and amino acids for HB production

Question 19

which energy pathway for RBC to get ATP

Answer 19

• RBC need glycolysis for ATP (no oxidative metabolism bc no mitochondria)

Question 20

what antioxidant to RBC have

Answer 20

• RBC have glutathione stores when in high oxygen and cant make new proteins need to be able to combat free radical production

Question 21

cytoskeleton in RBC - if absent what disorder does it cause

Answer 21

• Cytoskeletal proteins help RBC maintain shape –> disorder = loss of red cell mass (anemia)

Question 22

subunits in hemoglobin

Answer 22

2 alpha and 2 other chains

Question 23

what does each subunit in hemoglobin contain

Answer 23

o Each subunit has heme moiety containing iron to bind oxygen

Question 24

what is the majority type of hemoglobin and what is less

Answer 24

• 97% is HbA (2 alpha, 2 beta chains)
  o 2% is HbA2 (2 alpha, 2 delta chains)

Question 25

fetal hemoglobin

Answer 25

o Fetal Hb (2 alpha, 2 gamma) – very high affinity for oxygen bc cant bind 2,3 DPG well

Question 26

what has a higher affinity for hemoglobin that oxygen

Answer 26

- Carbon monoxide has 200x higher affinity for Hb than oxygen o Forms carboxyhemoglobin

Question 27

how is heme made

Answer 27

- Heme is made through reactions with glycine and succinyl-CoA precursors

Question 28

what is the hemoglobin dissociation curve what 4 things decrease hemoglobin affinity for oxygen****

Answer 28

1. increase temp 2. increase DPG 3. increase PCO2 4. decrease pH

Question 29

where are RBCs eliminated

Answer 29

by macrophages in spleen red pulp

Question 30

how is hemoglobin metabolized where does the iron go? where does the heme go? where does the globin go?

Answer 30

o Iron recycled and sent back to bone marrow o Heme eliminated in bile and stool as bilirubin o Globin is recycled into its component amino acids

Question 31

what happens to senescent (old) erythrocytes/ RBCs

Answer 31

- Senescent (old) erythrocytes are phagocytosed by macrophages and heme degraded into biliverdin then bilirubin and released into blood

Question 32

what is heme degraded into

Answer 32

degraded into biliverdin then bilirubin and released into blood o Unconjugated bilirubin carried to liver bound by albumin

Question 33

what is unconjugated bilirubin carrier to the liver by

Answer 33

albumin

Question 34

where is bilirubin conjugated and how

Answer 34

in the liver o Add 1-2 residues of glucuronic acid o Catalyzed by uridine diphosphate glucanosyltransferase (UDG)

Question 35

how is conjugated bilirubin excreted

Answer 35

- Bilirubin glucuronide excreted into bile

Question 36

where is iron absorbed

Answer 36

duodenum

Question 37

what is better absorbed fe2+ or fe3+

Answer 37

fe2+

Question 38

how is iron transported

Answer 38

o Transported through divalent metal transporter (DMT)

Question 39

what prevents iron overload

Answer 39

hepcidin

Question 40

hepcidien function

Answer 40

o Excess iron can damage cells so liver transport iron from enterocytes into bloodstream via hepcidin  Hepcidin prevents iron overload

Question 41

what does hepcidin block

Answer 41

ferroportin transporter

Question 42

what is hepcidin stimulated by

Answer 42

inflammation IL-6

Question 43

what is hepcidin inhibited by

Answer 43

reduced iron stores and erythroferrone (released by developing erythroblasts)

Question 44

what does transferrin transporter accept iron from

Answer 44

- Transferrin transporter transport iron though blood o Accepts iron from ferroportin

Question 45

cells with transferring receptors do what

Answer 45

- Cells with transferrin receptors can endocytose transferrin and store it in ferritin protein complex

Question 46

where is iron stored

Answer 46

- Store iron in hepatocytes, spleen, and bone marrow

Question 47

storage form of ferritin is

Answer 47

hemosiderin

Question 48

what % of anemia is iron deficiency anemia

Answer 48

50%

Question 49

causes of iron deficiency anemia

Answer 49

- Lack of iron in diet, parasites stealing iron, increased iron requirements in childhood or pregnancy, menstruation, trauma, GI bleed

Question 50

iron requirements for male and female

Answer 50

- Male: 15 mg/d with 6% absorption - Female: 11 mg/d with 12% absorption

Question 51

what increases the absorptionn of iron and what decreases it

Answer 51

- If iron deficient can increase absorption by 20% if meat, but 5-10% if vegetarian o Vegetarians; phytates and phosphates reduce iron absorption by 50%

Question 52

symptoms of iron deficiency

Answer 52

fatigue, dyspnea, exercise intolerance o Blood loss: metorrhagia, hematochenzia, melena, hematuria

Question 53

signs of iron deficiency

Answer 53

pallor (conjunctiva), tachycardia, flow murmur

Question 54

labs for iron deficiency anemia

Answer 54

o labs: abnormal CBC Low CBC count, reduced Hb [ ], reduced reticulocytes, microcytic and hypochromic RBC, increased red cell distribution width - Severe: size (anisocytosis) and shape (poikocytosis) changes in microcytic and hypochromic RBC - Labs: iron o Decreased ferritin and serum iron, increased total iron binding capacity

Question 55

morphology in iron deficiency anemia

Answer 55

microcytic and hypochromic

Question 56

what's impacted in early iron store depletion

Answer 56

marrow iron stores, serum ferritin, total iron binding capacity (TIBC)

Question 57

progression of iron deficiency

Answer 57

- Initially: ferritin drops, TIBC increases - Then: serum iron and transferrin saturation drop - Late: CBC abnormal; hypochromic, microcytic anemia - Blood Hb [ ] drop

Question 58

alsolute iron deficiency vs functional iron deficiency

Answer 58

Absolute iron deficiency: Reduction of total body iron stores, which may progress to IDA Functional iron deficiency: Iron is inadequately mobilized from stores to the circulation and erythropoietic tissue.

Question 59

causes of absolute iron deficiency

Answer 59

-increased demands -decreased intake -decreased absorption -chronic blood loss

Question 60

causes of functional iron deficiency

Answer 60

-chronic inflammation and elevated hepcidin levels (i.e. IBD, kidney disease, autoimmune, infection) -increased erythropoiesis (ESA therapy or endogenous response to anemia)

Question 61

iron stores in functional iron defieincy

Answer 61

could be normal or high