quiz 3.1 blood to heme Flashcards
occurs when the endothelium lining blood vessels is damaged or removed
thrombosis
first and intiial step in hemostasis of injured vessels
vasocon
3 phases shared by hemostasis and thrombosis
platelet aggre
fibrin mesh formation
dissolution
3 types of thrombi
white
red
fibrin deposits
phase wherein platelets bind to collagen at the site of vessel wall injury, form TXA2 and release ADP
platelet aggre
this binds to the paltelet aggregate making it more stable
fibrin mesh
a phase involving plasmin
dissolution
thrombus that is relatively poor in RBC, found in rapid blood flow vessels
white fibrin
thrombus found in vessels where blood is retarded or there is stasis with or without injury
red fibrin
fibrin found in capillaries or small vessels
fibrin deposits
types of coagulationf actors
zymogen cofactor fibrinogen transglutaminase regulatory and other proteins
in vitro, the intrinsic pathway can be activated by
negatively charged surfaces
common name factor 1
fibrinogen
common name factor 2
prothrombin
common name factor 3
tx factor
common name factor 4
calcium
common name factor 5
proaccelerin
common name factor 7
proconvertin
factors under ex. pathway
7
3
factors under itnrinsic
12
11
9
8
PK
HMWK
first common factor for ex and int pathways
10
the ext. pathway is initiated at the site of ___ with the exposure of _____
tx injury
tx factor
TF acts as a cofactor for ____, enhacning its enzymatic activity
7
activation of factor 10 requires what complex
extrinsic tenase complex (Ca-TF-fac 7a)
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
PT
a measure of the intrinsic pathway
aPTT
used to monitor heparin therapy
PTT
used to monitor warfarin therapy
PT
“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
- 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
PP
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
PP
possible tx for porphyrias
glucose loading
hematin
b-carotene
dse of no ferrochelatase
PP
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
