Hb synthesis and catabolism, choudhury

Question 1

structure of heme

Answer 1

porphyrin ring structure with one Fe atom chelated in center by 4 N atoms
reversible O2 attachement

Question 2

1 Hb can carry how much O2

Answer 2

4 molecules

Question 3

how does nonheme get absorbed

Answer 3

as Fe2+ so through DMT1 driven by H+ gradient

Question 4

how is Fe2+ transported to basolateral membrane

Answer 4

mobilferrin

Question 5

how is heme iron absorbed

Answer 5

duodenal epithelial cells via binding or endocytoses

Question 6

what breaks down heme iron in enterocyte

Answer 6

heme oxygenase, release CO and biliverdin

Question 7

What happens to dietary Fe3+ before absorption

Answer 7

recuded at extracell apical membrane by ferric reductase prior to absorption

Question 8

Fe2+ exits enterocyte how and then what happens

Answer 8

ferroportin

converted back to Fe3+ by haphaestin and binds to transferrin

Question 9

decreased apoferritin synthesis from liver disease changes iron levels how

Answer 9

elevated serum iron levels because apoferritin is the storage mech

Question 10

what is hepcidin and its mech

Answer 10

peptide secreted by hepatocytes that causes degradation of ferroportin to reduce dietary iron absorption

Question 11

what occurs in loss of hepcidin production

Answer 11

hemochromatosis. Fe overload

Question 12

what happens in increase hepatice release of hepcidin

Answer 12

anemia of chronic disease by blocking Fe absorption

Question 13

what is first step of heme synthesis and where does it occur

Answer 13

succinyl CoA and glycing make ALA in the mitochondria

Question 14

how and where is porphobilinogen formed

Answer 14

2 ALA via ALA dehydratase make porphiliniogen in the cytosol

Question 15

what disorders are cause by mutations in ALA dehydratase (porphobilinogen synthase)

Answer 15

porphyria and Pb poisoning

Question 16

sideroblastic anemia is caused by a mutation where

Answer 16

aminolevulnic acid synthase (makes ALA) in mitochondria

Question 17

porphyria can be caused by what mutations

Answer 17

ALA dehydratase and PBG deaminase

Question 18

where and what converts protoporphyrin to heme

Answer 18

in mitochondria

ferrochelatase

Question 19

too much of this substance can inhibit ferrochelatase

Answer 19

lead

Question 20

what is the rate limiting step for heme synthesis

Answer 20

ALA synthase in mitochondria

Question 21

what gives negative feedback on ALA synthesis

Answer 21

heme

Question 22

protoporphyria is caused by mutation where

Answer 22

ferrochelatase

Question 23

where does globin synthesis occur

Answer 23

cytoplasm of normoblasts and reticulocytes

Question 24

which chromosome encodes for alpha globin? beta?

Answer 24

alpha on chrom 16

beta on 11

Question 25

disruption in balance of globin chains is called what

Answer 25

thalassemia

Question 26

what are the embryonic forms of Hb

Answer 26

Gower I and II | II has alpha 2 globin and epsilom

Question 27

what are the fetal forms of Hb

Answer 27

Hb portland and HbF

Question 28

most abundant fetal form Hb

Answer 28

HbF

Question 29

what are the adult Hb

Answer 29

HbA2 and HbA1

Question 30

most prevalent adult Hb and components

Answer 30

HbA1 | 2alpha and 2beta

Question 31

where does heme join globin chains

Answer 31

cytoplasm in RBC of marrow

Question 32

what is needed for normal Hb synthesis

Answer 32

Fe

Question 33

what is the functional Fe pool

Answer 33

Hb, myoglobin, enzymes

Question 34

what is the storage iron pool

Answer 34

ferritin, hemosiderin

Question 35

Hb can only bind Fe in what form

Answer 35

ferrous 2+

Question 36

how many bonds does Fe2+ make with hemoglobin

Answer 36

6 4 heme 1 globin 1 reversible to O2

Question 37

most common cause anemia

Answer 37

Fe deficiency

Question 38

how does heme iron enter enterocyte

Answer 38

endocytosis or binding then split into Fe3+ by heme oxygenase then enterocytes convert it to Fe2+

Question 39

what are the energy metabolism mech of RBC

Answer 39

glycolysis! | pentose phosphate cycle

Question 40

what is created in glycolysis in RBC

Answer 40

ATP for ion pumps and NADH for re-oxidation of Hb

Question 41

what is created in pentose phosphate cycel

Answer 41

NADPH to maintain reduced state glutathione and sulfhydryl groups

Question 42

how is hemolysis of RBC detected

Answer 42

hemoglobinemia annd hemoglobinuria

Question 43

what is Hb degraded into and by what?

Answer 43

macrophages of reticuloendothelial system into 3 parts | Fe, protoporphyrin and globin

Question 44

what happens to protoporphyrin ater heme breakdown

Answer 44

converted to biliverdin which is converted to unconjugated bilirubin

Question 45

what is methemoglboin

Answer 45

Hb carrying ferric iron, cannot carry O2 now

Question 46

hwo does body protect itself from increase methemoglobin levels

Answer 46

methemoglobin reductase from RBC

Question 47

what is sulfhemoglobin

Answer 47

partially denatured Hb | usually from sulfa containing drugs or aromatic amine drugs

Question 48

what is carboxyHb

Answer 48

CO Hb

Question 49

What is structure of HbF

Answer 49

2 alpha, 2 gamma

Question 50

how do we Tx infants with increased unconj bilirubin

Answer 50

light therapy changes trans to cis which is easily excreted in urine

Question 51

what catalyzes unconj to conj bilirbuin in SER

Answer 51

UDPGT

Question 52

When is urinary urobilinogen increased

Answer 52

hyperbilirubinemia

Question 53

when you see increased urinary bilirbuin what does this indicate

Answer 53

increased serum conjugated bilirubin

Question 54

water soluble bilirubin is same as what

Answer 54

conjugated

Question 55

What is Gilberts and findings

Answer 55

enzyme mutation impairing hepatocellular funciton hepatic jaundice total serum bilirubin mainly unconjugated, increased urinary

Question 56

what is Crigler-Najjar type I syndrome and findings

Answer 56

hepatic jaundice enzyme mutation/defective conjugation increased serum unconjugated bilirubin and increase urinary urobilinogen

Question 57

what isdubin johnson syndrome and findings

Answer 57

haptic jaundice defective secretion from hepatocyte increased serum conjugated bilirubin

Question 58

what can cause increase in direct and indirect bili

Answer 58

hepatitis with lowered conjugation or excretion

Question 59

what are findings of post hepatic jaundice

Answer 59

increased serum and urine conjugated bili dec urobilin and stercobilin clay colored stools!!!! no urinary urobilinogen

Question 60

what causes sickle cell trait

Answer 60

missense mutation beta globin chain | position 6 valine for glutamic acid

Question 61

Hb S replaces what Hb

Answer 61

HbF | occurs around 6 mo

Question 62

what results from sickle cell disesase

Answer 62

hypozic tissue injury from microvascular occlusions from abnormal RBC shape painful muscle aches and pains

Question 63

sickle cell patients have what level bilirubin

Answer 63

increased, may have jaundice

Question 64

what type of anemia is characteristic of thalassemias

Answer 64

microcytic hypochromic anemia with target cells!!! on peripheral smear

Question 65

what is alpha thalassemia

Answer 65

impaired produciton alpha chains

Question 66

what are types of alpha thalassemias

Answer 66

Hb H disease: 3 beta 1 alpha | Thalassemia major: loss all 4 alpha so results in hydrops fetalis

Question 67

what occurs in beta thalassemia

Answer 67

elevated HbF and A2 because impaired beta globin synthesis

Question 68

What is cooleys anemia

Answer 68

beta thalassemia major homozygous severe anemia that requires lifelong transfusions

Question 69

what is Tx for beta thalassemia minor

Answer 69

heterozygous | genetic counseling but really nothing

Question 70

clinical signs of beta thalaseemia

Answer 70

prominent protruding forehear and flattened nose hyperplastic marrow? "hair on end"