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Medical Biology- Spring > HCP 2 > Flashcards

HCP 2 Flashcards

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1
Q

What are the 2 (ionic) forms of iron?

A

Ferrous iron (Fe2+)

Ferric iron (Fe3+)

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2
Q

What are the two dietary forms of iron?

What are the dietary sources of each?

A

Heme bound iron: animal derived (beef, eggs, fish, liver)

Non-heme bound iron: plant derived (spinach, beans)

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3
Q

In what ionic form is iron transported in the blood and stored in the body? Why must it be in this form?

A

Ferric iron (Fe3+)

Ferrous iron (Fe2+) is very reactive ➡️ catalyzes formation of free radicals & ROS

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4
Q

How is ferric iron absorbed into enterocytes?

A

1) reduced from Fe3+ ➡️ Fe2+ via ferric reductase (duodenal cytochrome b) in apical membrane of enterocytes
2) transported from lumen into enterocytes via DMT1 (driven by H+ gradient)

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5
Q

How is heme bound iron transported into enterocytes?

A

via brush border protein or endocytosis (exact mech unknown)

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6
Q

In enterocytes, how is iron freed from heme?

A

Oxidized via heme oxygenase ➡️ CO + biliverdin + free Fe3+

Free Fe3+ reduced to Fe2+ in enterocyte

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7
Q

What protein transports free Fe2+ in enterocyte to basolateral membrane?

A

Mobilferrin

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8
Q

What steps occur to transport Fe2+ out of enterocytes ➡️ transport in blood?

A

1) Fe2+ transported out of enterocytes via ferroportin 1 (FP1)
2) Fe2+ oxidized to Fe3+ via hephaestin (iron oxidase)

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9
Q

What protein binds to Fe3+ iron for transport in the blood?

A

Transferrin

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10
Q

What protein regulates iron absorption? What cells secrete this protein?

How does it regulate iron absorption?

A

Hepcidin

Kupffer cells (liver)

Iron levels ⬆️ ➡️ hepcidin binds to DMT1 & FP1 ➡️ endocytosis & degradation ➡️ ⬇️ iron absorption

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11
Q

What are the substrates in the heme synthesis pathway? (Initial substrates ➡️ heme)

A

(mitochondria): Glycine + Succinyl CoA ➡️ delta-Aminolevulinic acid (ALA)

(Cytosol): ALA ➡️ Porphoblinogen ➡️ Hydroxymethylbilane ➡️ Uroporphyrinogen III ➡️ Coproporphyrinogen III ➡️ oxidized in mitochondria intermembrane space to Protoporphyrinogen IX

(Mitochondria): Protoporphyrinogen IX ➡️ Protoporphyrin IX (with Fe2+) ➡️ Heme

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12
Q

What are dietary sources of vitamin B12?

A

Animal products (meat, fish, shellfish, eggs)

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13
Q

How is vitamin B12 freed from ingested dietary protein?

A

In stomach:

1) Hydrochloric acid (from parietal cells
(2) pepsin (pepsinogen from chief cells ➡️ pepsin, activated via HCl)

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14
Q

What molecule does free vitamin B12 bind to in the stomach?

Where is this molecule secreted from?

A

R protein (haptocorrin): protects B12 from acidic gastric environment

R protein secreted by salivary glands

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15
Q

How is vitamin B12 freed from R protein? Where does this occur?

What molecule does vitamin B12 then bind to? Where is this molecule from?

A

In duodenum: R protein degraded via pancreatic proteases

Free B12 binds to intrinsic factor, IF (secreted by chief cells in stomach)

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16
Q

Where in the GI tract is vitamin B12 absorbed? How is it absorbed?

A

Absorbed in ileum

Vitamin B12-IF complex binds to cubulin receptors in ileum ➡️ taken up into enterocytes via endocytosis

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17
Q

What protein does vitamin B12 bind to for transport in the blood?

A

Transcobalamin II (TCII)

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18
Q

What are the main two reactions in the body that require vitamin B12 as a cofactor?

A

1) Conversion of homocysteine + N5-methyl-THF ➡️ methionine + THF (via methionine synthase)
2) Conversion of methylmalonyl CoA ➡️ succinyl CoA (via methylmalonyl CoA mutase)

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19
Q

Why can a vitamin B12 deficiency impact DNA synthesis?

A

⬇️ vit B12 levels ➡️ ⬇️ methionine levels ➡️ body converts folate stores to N5-methyl-THF (irreversible) ➡️ ⬇️ THF ➡️ ⬇️ N5,N10-methylene THF & ⬇️ N10-formyl THF ➡️ ➡️impaired DNA synthesis

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20
Q

What are the dietary sources of folate?

A

Spinach, beans, liver, leafy & dark green veggies

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21
Q

What are the two forms of folate?

A

1) Dietary folate: folate polyglutamate (PteGlu7)

2) Medicinal folate: pteroylmonoglutamate (PteGlu1)

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22
Q

What enzyme deconjugates dietary folate for absorption into enterocytes?

What metal cofactor is required for the function of this enzyme?

A

Folate conjugase (brush border peptidase): Deconjugates PteGlu7 ➡️ PteGlu1 (removes glutamate residues)

Zinc

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23
Q

What part of the GI tract is folate absorbed? How does folate enter enterocytes?

Study These Flashcards
A

Jejunum

Brush border PteGlu1 carrier

24
Q

What is the active form of folate in the body?

Where does conversion of ingested folate ➡️ active form occur?

Study These Flashcards
A

Tetrahydrofolate (THF)

Liver: PteGlu1 ➡️ Dihydrofolate ➡️ THF

25
What is the function of THF, as N10-formyl THF, in the body?
Purine synthesis (adenine, guanine) ➡️ needed for DNA synthesis
26
What is the function of THF, as N5,N10-methylene THF, in the body?
Thymine monophosphate (dTMP) synthesis ➡️ needed for DNA synthesis
27
What is the function of THF, as N5-methyl THF, in the body?
Methionine synthesis from homocysteine
28
What is the general composition of the RBC membrane, by %?
50% protein 40% lipid 10% carbohydrate
29
RBC membrane skeleton proteins: Alpha & beta spectrin ➡️ function?
Gives RBCs ability to stretch & reform Form geodesic dome shape ➡️ important in maintaining biconcave shape of RBCs
30
RBC membrane skeleton proteins: Ankyrin ➡️ function?
Connect alpha & beta spectrin tetramers to Band 3
31
RBC membrane skeleton proteins: Protein 4.1 ➡️ function?
Attaches to alpha & beta spectrin and actin
32
RBC membrane skeleton protein: Protein 4.2 ➡️ function?
Enhances interaction of ankyrin to plasma membrane
33
RBC membrane skeleton proteins: Actin ➡️ function?
Tail of alpha & beta spectrin attached to actin Actin also attached to protein 4.1
34
Integral RBC membrane proteins: Glycophorins A, B, C ➡️ function?
High sialic acid content Glycophorin A & B: Highly glycosylated ➡️ gives RBCs (-) charge ➡️ highly hydrophilic ➡️ RBCs do not adhere to each other or endothelium Glycophorin C: associated with protein 4.1 ➡️ ⬆️ binding between membrane and skeleton
35
Integral RBC membrane proteins: Band 3 ➡️ function?
Extracellular domain: has blood group antigen Cytosolic domain: binds to carbonic anhydrase II ➡️ enables exchange of HCO3- (in) and Cl- (out) at tissues HCO3- (out) and Cl- (in) at lungs
36
What is the diameter of an RBC?
6-7 micrometers
37
Where is bone marrow found?
Medullary canals of long bones and small cavities of cancellous/spongy/trabecullar bone
38
What are the 2 types of bone marrow?
1) red bone marrow: site of erythropoiesis | 2) yellow bone marrow: contains adipocytes
39
What are the anatomical features of red bone marrow?
``` Reticular connective tissue stroma Hematopoietic cords (islands) Sinusoidal capillaries w/discontinuous endothelium (between hematopoietic cords) ```
40
At what stage in erythropoiesis does erythropoietin (EPO) act? Where is EPO secreted from?
Stimulates conversion of Burst-forming unit erythroid cells (BFUE) ➡️ colony-forming unit erythroid cells (CFUE) Kidneys (major) and Liver (minor)
41
At what stage in erythropoiesis does heme synthesis occur?
Basophilic erythroblasts
42
Which cell stage in erythropoiesis is: 1) mostly basophilic? 2) both basophilic and acidophilic? 3) mostly acidophilic?
1) basophilic erythroblast 2) polychromatophilic erythroblast 3) orthochromatophilic erythroblast (normoblast)
43
Erythropoiesis: What causes basophilia? What color dye stains basophilic cells? What causes acidophilia? What color dye stains acidophilic cells?
Basophilic: due to ⬆️ polysomes, stains blue Acidophilic: due to ⬆️ hemoglobin, stains pink
44
At what stage in erythropoiesis does extrusion of the nucleus occur?
Orthochromatophilic erythroblasts
45
At what stage in erythropoiesis does lose of polyribosomes occur?
Reticulocytes
46
How is anemia diagnosed, using lab values?
⬇️ hematocrit (ratio of RBCs to total blood volume) ⬇️ [hemoglobin]
47
Specific to case 2, what can cause microcytic anemia? What can cause macrocyctic anemia?
Iron deficiency ➡️ Microcytic anemia Vitamin B12 or folate deficiency ➡️ Macrocytic anemia
48
What are the morphological features of microcytic anemia?
RBCs appearance: 1) Small (microcytic) 2) Pale (hypochromic), with enlarged zone of pallor (hemoglobin at peripheral rim) 3) Poikilocytosis (small & elongated)
49
What are the morphological features of macrocytic anemia?
RBCs appearance: 1) large (macrocytic) and oval-shaped 2) hyperchromic (due to adequate hemoglobin) 3) variation in size (anisocytosis) and shape (poikilocytosis) 4) low reticulocyte count 5) may be nucleated
50
What are the shared characteristics of hemolytic anemias?
1) ⬇️ RBC lifespan (10-20 days less than the normal 120 days) 2) ⬆️ EPO levels ➡️ ⬆️ in erythropoiesis 3) RBC hemolysis ➡️ accumulation of hemoglobin degradation products
51
What is the inheritance pattern of hereditary spherocytosis?
Autosomal dominant (75% of cases) Compound heterozygosity (inheritance of 2 different defects) in 25% of cases
52
What are the most common mutations in hereditary spherocytosis?
Frameshift or nonsense mutations of alpha-spectrin, beta-spectrin, ankyrin, band 4.2, or band 3 RBC proteins ➡️ synthesis of these proteins
53
What is the morphology of RBCs in hereditary spherocytosis?
Small | Hyperchromic, lack central zone of pallor
54
What is the anatomical location of the spleen?
L upper quadrant of abdominal cavity (protected by ribs 9, 10, 11)
55
What are the two main components of the parenchyma of the spleen? What are the functional parts of each component?
White pulp (20% of spleen): periarteriolar lymphoid sheaths (PALs), lymphoid nodules, marginal zone (bet. red & white pulp) Red pulp (Majority of spleen): splenic cords (cords of Billroth), splenic sinusoids
56
How big are the slits between the stave cells of the splenic sinusoids?
less than or equal to 2-3 micrometers

Medical Biology- Spring (8 decks)

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