quiz 3.1 blood to heme Flashcards by Zeth Renae Raquedan

occurs when the endothelium lining blood vessels is damaged or removed

thrombosis

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first and intiial step in hemostasis of injured vessels

vasocon

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3 phases shared by hemostasis and thrombosis

platelet aggre
fibrin mesh formation
dissolution

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3 types of thrombi

white
red
fibrin deposits

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phase wherein platelets bind to collagen at the site of vessel wall injury, form TXA2 and release ADP

platelet aggre

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this binds to the paltelet aggregate making it more stable

fibrin mesh

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a phase involving plasmin

dissolution

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thrombus that is relatively poor in RBC, found in rapid blood flow vessels

white fibrin

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thrombus found in vessels where blood is retarded or there is stasis with or without injury

red fibrin

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fibrin found in capillaries or small vessels

fibrin deposits

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types of coagulationf actors

zymogen
cofactor
fibrinogen
transglutaminase
regulatory and other proteins

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in vitro, the intrinsic pathway can be activated by

negatively charged surfaces

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common name factor 1

fibrinogen

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common name factor 2

prothrombin

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common name factor 3

tx factor

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common name factor 4

calcium

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common name factor 5

proaccelerin

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common name factor 7

proconvertin

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factors under ex. pathway

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factors under itnrinsic

12
11
9
8

PK
HMWK

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first common factor for ex and int pathways

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the ext. pathway is initiated at the site of ___ with the exposure of _____

tx injury

tx factor

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TF acts as a cofactor for ____, enhacning its enzymatic activity

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activation of factor 10 requires what complex

extrinsic tenase complex (Ca-TF-fac 7a)

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TF nad factor 7a activates what shit in the intrinsic pathway

factor 9

major physiologic inhibitor of coag

TF pahway inhibitor (TFPI)

how does TFPI inhibit coag

TFPI + factor 10a inhibits TF-7a complex

links the intrinsic and extrinsic pathway

factor 10

main action of thrombin

activates fibrinogen

a highly specific transglutaminase that is activated by fibrinogen

factor 8a

important natural inhibitor of coagulation, genetic deficiency of this protein can result in thrombosis

antithrombin

the endogenous activity of antithrombin is greatly potentiated by the ____________

presence of sulfated GAGs (heparans)

the action of heparin can be strongly antagonized by cationic polypeps like

protamine

the regulatory mechanism of thrombin is attirubted to its acility to combine with

thrombomodulin

a genetic deficiecny of either ___ or ____ can cause venous thrombosis

protein C or S

px with ______ have a increased risk for venous thrombosis

factor 5 Leiden

why higher risk sa venous thrombosis ang may Leiden

Leiden cannot be inactivated by APC

APC degrades

factors 5a and 8a

vit-K dependent facotrs

``` 2 7 9 10 protein C and S ```

why vit-K dependent ang 2 7 9 10

they need vit-K dependent y-carboxylation of glut resideues to function

what inhibits the y-carboxylation in vit-K dependents

warfarin

warfarin inhibits what specifically

y-carboxylation

during synth of factors, vit-K is important in modification and formation of

gamma-carboxyglutamate

coumarin or heparin: which is instantaneous

heparin

coumarin or heparinL which takes days to take effect

coumarin

a predicatable administration of inihibitors of thrombin

oral

most common hemophilia

hem A

hemophilia A is deficiency of

factor 8

hempphilia B is deficiecny of

factor 9

most common genetic bleeding disorder

von Willebrand factor

a large multimeric glycoprotein that stabilizes factor 8

von Willebrand factor

functions of von Willebrad

stabilize factor 8 | promotes platelet adhesion

fibrin clots are dissolved by

plasmin

activates plasminogen

tx plasminogen activator

the fast-acting inhibitor of plasmin

a2-antiplasmin

activators of plasminogen all cleave what

arg-val bond

the carboxypeptidase that can inhibit fibrinolysis by removing the terminal lysines from fibrin

thrombin activatable fibrinolysis inhibitor (TAFIa)

the second activator of plasminogen

urokinase

main action of urokinase

degrades ECMatrix

t-PA is marketed as _____ is produced by recombinant DNA methods

alteplase

t-PA or streptokinase: which is selective

t-PA

three steps in hemstatic plugs by paltelet

adhesion secretion aggregation

platelets adhere to ____ via _____

collagen GPIa-IIa GPIb-IX-V

the binding of GPib-IX-V is mediated via

von Willebrand

granules found in and released by platelet

dense and alpha

most potent activator of platelet and initiator of activation

thrombin

the further events leading to platelet activation upon binding of PAR-1 and 4 are examples of

outside0in transmembrane signaling

signaling wherein chemical messenger outside the cell generates effector molecules inside the cell

outside-in transmembrane signaling

phospholipase Ca hydrolyzed PIP2 to form what effectors molecules

IP3 | DAG

cytosolic phospholipase A2 liberates arachidonic acid to form

TXA2

TXA2 promotes or inhibits platelet aggreg?

promotes

potent inhibitor of platelet aggregation produced by endothelial cells

prostacyclin

action of prostacyclin is via

cAMP formation > decreasing calcium

roles of endothelial cells in inhibiting platelet activities

ADPase PGI2 heparan sulfate plasminogen activators

an antiplatelet drug

aspirin

how does aspirin inhibit paltelets

inhibits production of thromboxane A2/COX1

full name of aspirin

acetylsalicylate

a potent aggregator of platelets and vasocon

TXA2

antiplatelet drugs

clopidogREL prasugREL ticagRELor

overall test for paltelet and vessel wall function

skin bleeding time

in vitro test of platelet-related hemostasis

closure time

a measure of the extrinsic pathway

a measure of the intrinsic pathway

aPTT

used to monitor heparin therapy

PTT

used to monitor warfarin therapy

"circulating tissue"

blood

fluid in an uncoagulated bllod

plasma

fluid in a coagulated blood

serum

blood comprises ___ of the total body weight

7-8%

normal blood pH

7.35-7.45

normal volume of blood

5-6L in M | 4-5l IN Fe

normal sp.gr. of blood

1.035-1.075

the ability of stem cells to generate specialized cell types

potency

a stem cell that is capable of producing all the cells in an organism

totipotent

a stem cell that produce only cells of a closely related family

pluripotent

a stem cell that produce only one type of cell

unipotent

embryonic or adult stem cells: which is limited in capability to differentitate

adult

common lymphoid progenitor gives rise to

B cells T cells NK cells plasmacytoid dendritic cells

common myeloid progenitor gives rise to

monocytoid dendritic cells granulocyte-monocyte progenitor megakaryocte-erythroid progenitor

cytokine that plays an important role in the proliferation of hematopoietic stem cells and some of their progeny

stem cell factors

glycoprotein imporatnt in regulating the rpoduction of platelets

thrombopoietin

cytokines produced by leukocytes that regulates various aspects of hematopoiesis

interleukins

hemoglobin comprises ___ of RBCs

33%

normal RBC count

4. 6M in Fe | 5. 2M in M

RBCs that still contain RNA of the ribosomes and elements of the ER is called

retics

erythropoiesis uses what

erythropoietin IL-3 thrombopoietin

EPO is synthesized mainly by the ___ and released in response to ___

kidney | hypoxia

RBCs are dependent on ____ to generate ATP

glycolysis (anaerobic)

_______ is a variant of hgb that cannot transport oxygen

methemoglobin

_____ reduces the ferric of methemoglobin to ferrous restoring its function

cytochrome b5 reductase

RBCs depend on what 2 ways for production of energy

Embden-Meyerhoff (anaerobic) | HMP shunt

3 important products of anaerobic glycosis

NADH ATP 2,3-DPB

the most important product of PPP/HMP

NADPH

principal determinant of shunt flow in the PPP is

NADP-NADPH ratio

H2O2 can be detoxified by the most active enzyme in the RBCs

catalase

the protein involved in the facilitated diffusion of glucose

GLUT1

GLUT1 exhibits specificity for __ and ____

glucose | related D-glucose

dependent or indepdent of insulin: GLUT1?

insulin-indepedent

retics has __ and __ for energy production

glycerol kinase | glycerol

active in protein synthesis: RBC or retics?

retics

once retics are released into the circulation, they lose their organelles within

24hrs

what is injected in rabbits to hemolyze and induce prod of retics

phenylhydrazine

the tail end of this spectrin binds to ___

actin

actin binds to spectrin and ___

protein 4.1

a globular protein that binds tightly to the tail end of spectrin near the actin-binding site

protein 4.1

sugar moiety of bld grp A

N-acetylgalactosamine

sugar moiiety of bld grp B

galactose

the secretor genes code for

fucosyl transferase

presence of glycoproteins of ABO substances are determined by

Se(secretor) gene

NV WBC

4k-10k/uL

how does WBCs move

thru ameboid motion and diapedesis

neutropenia is most likely to occur when

chemotherapeutic regimens and after bone marrow transplantation

the acute inflammatory response by neutrophils include

increase vascular permeability entry of activated neutro activation of platelet spontaneous subsudence if successful

used in adhesion of enutro to endothelial cells

integrins

mutations affecting the NADPH oxidase system causes

chronic granulomatous dse

the respiratory burst of phagocytic cells involves ____ and helps kill bacte

NADPH oxidase

chemokines are stabilized by

disulfide bonds

basophils secrete what

histamine | heparin

phagocytes internalize invading microorganisms inside _____

phagosomes

honeycomb channel that icnreases surface area in platelets

open canalicular system

the mitochondria of paltelets enable them to generate ATP via

b-oxidation of fatty acids

formation of enlarged hyperreactive paltelets, resulting in an higher risk for thrombosis

acute coronary syndrome

autoimmune disorder marked by depressed platelet count caused by generation of autoantibodies

immune thrombocytopenic purpra

antibodies that attack not only the endogenous but also dontaed paltelets

alloantibodies

dse where Abs from mom's circu cross the placenta and attack platelets in the fetus

neonatal alloimmune thrombocytopenia

can be induced by tamoxifen, ibuprofen, vancomycin, and many sulfonamides

thrombocytopenia

dse of infants characterized by progressive kidney failure, thrombocytopenia and hemolytic anemia

hemolytic-uremic sundrome

genetically inherited deficiency in GP1b

Bernard-Soulier

genetically inherited deficiecny in GPIIb/IIIa complex

Glanzmann thrombasthenia

highest affinity to the anode in electrophoresis

albumin

highhest afffinity to the cathode in electrophoresis

gamma

highest concentration among the proteins in electrophoresis

albumin

lowest conc among proteins in electrophoresis

alpha1

a protein that is an exception of the rule that all proteins has either N or O linked oligosacch

albumin

exhibits highest activity og any of the erythrocyte glycolytic enzymes

triose phosphate isomerase

principal stimulator of synthesis of acute phase reactants by hepatocytes

cytokine | IL-1

a transcription factor involveed in teh stimulation of synthesis of certain of the acute phase reactants

nuclear factor kappa-B

majormprotein in the palsma (60%)

albumin

use of solvents or electrolytes to remove diff. protein ractions in accordance to their solubility

salting-out method

in teh salting out method, proteins are separated into

albumin globulins fibrinogens

permits resolution of plasma proteins into five bands

electrophoresis

proteins under the alpha1-globulins

a1-acid glycoproteins a1-fetoglobulin retinol-binding a1-antitrypsin

proteins under the alpha2-globulins

ceruloplasmin haptoglobulins a2-macroglobulins

major glycoprotein in fetal plasma and amniotic fluid

a1-fetoglobulin

globulin that transports retinol

retinol-binding

retinol-inding protein forms a complex with

trasnthyretin

inhibits leukocytes proteases to protect the lungs from damage due to inflamm

a1-antitrypsin

lack in a1-antitrypsin leads to

emphysema

carries copper, and is named after its color due to high copper conc

cerulopasmin

protein that converts ferrous to ferric prior to incorporation of ferric into transferrin

ceruloplasmin

dse where there is low ceruloplasmin in plasma and high copper in brain and liver

wilson's dse

protein that forms acomplex with hgb which cannot be excreted from the kidneys preventing loss of free hgb

haptoglobulin

protein that binds to proteinases and the complex are rapidly cleared from the plasma

a2-macroglob

protein for transport of zinc in plasma

a2-macroglob

proteins under beta-globulins

``` transferrin hemopexin crp b2-microglobulin beta-LPP ```

transports iron in the circulation to sites where it is required

transferrin

a transferrin can hold how many ferrics

2 mol

binds heme after RBC breakdown and prevents its excretion

hemopexin

very small amount in plasma bcoz easily excreted due to low MW

b2-microglobulin

fraction made of immunglobulin/antibodies

gamma globulin

fibrinogen is increased during

mens preggy inflamm infec

in nephrotic syndrome, hepatic cirrhosis, glomerulonephritis, albumin is ___________

decreased

in dehydration, albumin is

increasded

in inflamm syndrome, a1-acid glycoprotein is

decreased

a1-fetoglob is increased in

acute hepa hepatoma preggy

hemopexin is increased in

injectiin of porphyrogenic drugs

children or adult: higher a2-macro

children

treatment or intervention for lack of heme

IV hemin

iron is almost always n ___ form int eh body

protein-bound

<1% of iron is in __ form

iron-sulfur clusters

26% of iron is in ______________ form

transport and storage

iron from ____________ is readily absorved

meat sources

rank the physical states of iron accdg to bioavailability

heme > ferrous > ferric

inhibitors of iron absorption

``` phytates tannins soil clay laundry starch iron overload antacids ```

competitors of iron absorption

``` lead cobalt strontium manganese zinc ```

facilitators of iron abosrption

``` ascorbate amino acids citrate iron deficiency stomach acid high alt exercise pregnancy ```

why is iron absorption tightly regulated in the proximal duodenum

no physiologic pathway for excretion

how does gastric acid help in iron absorption

lowers pH in duodenum

enterocytes reduce ferric to ferrous via

ferrireductase

transfer o iron from the apical surfaces of enterocytes into their interioirs is perfomred by

DMT1 divalent metal transporter

passage of iron across the basolateral mrmbarne is carried out by

iron regularory protein 1

the IREG1 may react with what copper-containign pritein

hephaestin

mechanism wherein further absortpion of iron is blocked if a sufficient amount has been taken up

muscosal block

iron forming a complex with apotransferrin is called

transferrin

transferrin is cmpsoed of

iron with apotransfferrin

how many iron transported per tranferrin

2 mol of ferric

__ and ___ maintain the conc. of free iron in the body fluids at avlues below 10^-10 mol L^-1

trasferrin and lactoferrin

how is iron itnernalized by endocytosis

binding to transferrin receptors

transferrin and lactoferrin are taken up into the cells by ___

receptor-mediated endocytosis

excess iron is stored as ______ and in _____

ferritin | liver

specific untranslated sequences of the mRNAs for both TfR and dferritin

iron response elements (IRE)

partly degraded form of ferritin but still containing irokn

hemosiderin

dse characterized by microcytic hypochromic RBCs, reduced iron uptake and/or excess excretionq

IDA

manifesstation of IDA that is the habitual ignestion of unusual substances like earth, clay, ice, etc

pica

dse that is excess irona bsorption, saturation of iron-binding proteisn, deposition of hemosiderin in tx

hereditary hemochromatosis

deposition of excess iron in the organs and skin produces ______________

bronze pigmentation (bronze dse)

mutation in hereditary hemochromatosis

cys282 to tyr | his68 to asp

primary cause of heredotary hemochromatosis is the inheritance of

autosomal recessive allele

differenc of secodnary from primary hemochromatosis

secodnary is not caused by mutation and is not inherited

cyclic compounds formed by linkage of four pyrrole rings through methenyl bridges

porphyrins

an example of porphyrin that contains amgnesium

chlorophyll

an example of porphyrin that contains iron

heme

A P A P A P A P

uroporphyrin 1

A P A P A P P A

uroporphyrin 3

M P M P M P M P

coproporphyyrin 1

M P M P M P P M

coproporphyrin 3

M V M V M P P M

heme

substituents in uropohphyrin

acetate | proprpionate

heme and protoporphyrin IX are what type of porphyrin

type 3

the four pyrrole rings in heme is connected by

methenyl bridges

what steps in heme synthe occurs in the mitochondria

1 6 7 8

what steps in heme synth occurs in the cytosol

2 3 4 5

1st step in heme synth

formation of ALA via ALA synthase

ALA is formed from

succnyl CoA and glycine

the coenzyme important to activate glycine for ALA synthesis

ALA synthase is inhibited by

heme

step 2 in heme synth

formation of porphobilinogen

the first itnermediate in heme synth that has pyrrole ring

porphobilinogen (PBG)

step 3 inn heme synth

fomration of HMB hydroxymethylbilane

HMB is formed from

condensation of 4 PBGs

enzyme invovled in step 3

uroporphyrinogen 1 synthase / PBG deaminase / HMB synthase

step 4 in heme synth

HMB cyclizes to form uroporphyrinogen 1 or 3

enzyme in step 4

uroporphyrinogen 3 synthase

the pyrrole rings in uroporphyrinogens are linked by

methylene bridges

step 5 in hem synth

uro 3 to copro 3

decarboxylation of uro 3 converts ____ to ____

acetate to methyl

step 6 -7 of heme synth

copro 3 enters mitochon to become protoporphyrinogen 3 then to protoporphyrin 3

enzyme in step 6-7

coproporphyrinogen oxidase

enzyme in step 8

ferrochelatase

step 8 of heme synth

incorporation of iron into protoppor

heme biosynth occurs in most mammalian cells except

mature RBC

the hepatic and erythroid form of ALA synthase are respectively called

ALAS1 | ALAS2

the rate-limiting rxn in heme synth sic atalyzed by

ALAS1

does glucose inhib or promote heme synth

inhibit

dse from abnormal metab of heme synth pathway

porphyria

3 most common porphyria

IAP PCT PP

enzyme lesion in the early stage of the pathway leads to accum of what

ALA and PBG

symptoms of accum of ALA and PBG

abdom pain | neuropsychiatric symptoms

enzyme lesion in the alter part of the heme pathway leads to accum of

porphyrinogebs

symptoms of accum of porphyrinogens

photosensitivity (400 nm)

PCT is diagnosed thru

urine

acquired disorder assoc. with estrogen and alcohol use

PCT

onlymanifestation in PCT

photosens

possible complication n PCT

hypertricosis | hirsutism

intiai and common amnifest of IAP

abdom pain

CNS abnormatlities from IAP may icnulde

sezure coma delirium

precipitating factors for IAP

sulfonamides barbi estrogen

mild photsens characterized by painful burning or stinging sensations, pruritus, eythema, edema

possible tx for porphyrias

glucose loading hematin b-carotene

dse of no ferrochelatase

dse of no uroporphyrinogen decarboxylase

PCT

enzyme in step 5

uroporphyrinogen decarboxy

dse of no uroporphyrinogen synthase

AIP

increased in ALA dehydratase deificnecy

urianry ALA | copro

tetrapyrrole ring of heme durign degradation is cleaved bet. ring 1 and 2 by

heme oxygenase

heme oxygenase cleaves between where

ring 1 and 2

the action og heem oxygenase produces

green biliverdin

biliverdin is reduced by ____ to form ______

biliverdin reductase | bilirubin

bilirubin is bound to ____ to be transported to liver

albumon

heaptocyte take the bilirubin and conjuagte it with

UDP-glucoronic acid

conjugation occurs thru _____________ forming ester type bonds between OH at C1 of glucorni acid carboxyl grps of bilirubin

UDP-glucoronosyltrasnferase

rate determining step in hepatic bilirubin metab

glucoronide synthesis

drug taht can induce both conjugate fomration and transport process

phenobarbital

results from accelerated hemolysis around the time of birth

neonatal physiologic jaundice

due to mutations int he gene encoding bilirubin-UGT

criggler-najar syndrome

due to mutations int he gene encoding bilirubin-UGT but is commonly benign

gilbert syndrome

due to hepatic parenchymal cell damage, impairing conjugation

toxic hyperbilirubinemia

this term includes all cases of extraheaotic obstrutive jaundice

cholestatic jaundice

mutations in the gene encoding MRP-2, the protein involved in the secretion of conjugated bili into bile

dubin-johnson

thought to be an abnormality in hepatic storaoge of bili

rotor