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Topic

RBC metabolism and membrane physiology

RBC metabolism and membrane physiology


Overview

Energy production processes of the RBC


Mechanisms to maintain heme iron in the reduced state


RBC membrane physiology

RBC Membrane Review

Explain the role of the RBC membrane in deformability



Explain how the osmotic balance of the erythrocyte is maintained

Energy production in the RBC



Characteristics of oxygen delivery

It does not require energy.

Energy production in the RBC



Oxygen delivery does not require _____

Energy

Energy production in the RBC



Oxygen _____ does not REQUIRE ______

energy

Energy production in the RBC



_______ transport does not ______ energy

Oxygen


require

Energy production in the RBC



________ does not require energy

Oxygen transport

Energy production in the RBC



Oxygen transport does not ___________

require energy

Erythrocyte metabolic processes requiring energy



Reading

Mainteneance of intracellular cationic electrochemical gradients



Maintaience of membrane phospholipids



Maintainence of skeletal protein plasticity



Maintenance of functional ferrous hemoglobin



Protection of cell proteins from oxidative phosphorylation



Initiation and maintenance of glycolysis



Synthesis of glutathione



Mediation of nucleotide salvage reactions

Erythrocyte metabolic processes requiring energy


Reading

Mainteneance of intraCELLULAR cationic electrochemical GRADIENTS



Maintaience of membrane PHOSPHOLIPIDS



Maintainence of skeletal PROTEIN plasticity



Maintenance of functional FERROUS hemoglobin



Protection of cell proteins from OXIDATIVE phosphorylation



Initiation and maintenance of GLYCOLYSIS



SYNTHESIS of glutathione



Mediation of NUCLEOTIDE salvage reactions

Erythrocyte metabolic processes requiring energy



Mainteneance of INTRA_________ cationic ELECTROCHEMICAL ________



Maintaience of MEMBRANE ____________



Maintainence of SKELETAL ___________ PLASTICITY



Maintenance of FUNCTINOAL ___________ HEMOGLOBIN



Protection of cell PROTEINS from ___________ PHOSPHORYLATION



INITIATION and maintenance of ____________



______________ of glutathione



Mediation of ____________ SALVAGE reaction

cellular


gradient



phospholipids



protein



ferrous



oxidative



glycolysis



synthesis



nucleotide

Erythrocyte metabolic processes requiring energy



Mainteneance of ______CELLULAR cationic _______________ GRADIENTS



Maintaience of _____________ PHOSPHOLIPIDS



Maintainence of _________ PROTEIN ________



Maintenance of __________ FERROUS ___________



Protection of cell ____________ from OXIDATIVE ________________



_____________ and maintenance of GLYCOLYSIS



______________ of glutathione



Mediation of NUCLEOTIDE_________ reactions

intra


electrochemical



membrane



skeletal


plasticity



functional


hemoglobin



protein


phosphorylation



initiation



synthesis



salvage


Various metabolic pathways in RBCs

Embden-Meyerhof pathway


Hexose monophosphate pathway


Methemoglobin reductase pathway


Rapoport-Lubering pathway

Various metabolic ___________ in RBCs



EMBDEN-Meyerhof _________


HEXOSE monophosphate __________


METhemoglobin reductase _________


RAPOPORT-Lubering __________

pathways



pathway


pathway


pathway


pathway

Various metabolic pathways in RBCs



Em_____-Meyerhof _________


Hex____ monophosphate pathway


____hemoglobin reductase pathway


Rap________-Lubering pathway

bden


pathway


ose


Met


oport

Various metabolic pathways in RBCs



_________-MeyerhOF pathway


_________ monoPHOSPHATE pathway


___________ reductASE pathway


___________-LuberING pathway

Embden


Hexose


Methemoglobin


Rapoport

Various metabolic pathways in RBCs



_______-Meyerh___ pathway


__________ mono__________ pathway


____________ reduct____ pathway


Rapoport-Luber___pathway

Embden


of


Hexose


phophate


Methemoglobin


ase


ing

Various metabolic pathways in RBCs



Embden-_______hof pathway


Hexose ______phosphate pathway


Methemoglobin _______ase pathway


Rapoport-______ing pathway

meyer


mono


reduct


luber

Various metabolic pathways in RBCs



Embden-___________ pathway


Hexose _____________ pathway


Methemoglobin _________ pathway


Rapoport-___________ pathway

meyerhof


monophosphate


reductase


lubering

Various metabolic pathways in RBCs



____________-Meyerhof __________


_________ monophosphate _________


__________ reductase ____________


____________-Lubering ___________

Embden


pathway



hexose


pathway



Methemoglobin


pathway


Rapoport


pathway

Various metabolic pathways in RBCs



Embden_____________________


Hexose _______________________


Methemoglobin _________________


Rapoport-___________________

meyerhof pathway


monophosphate pathway


reductase pathway


lubering pathway

Various metabolic pathways in RBCs

Embden-Meyerhof pathway


Hexose monophosphate pathway


Methemoglobin reductase pathway


Rapoport-Lubering pathway

Various metabolic pathways in RBCs



_______________________


Hexose monophosphate pathway


Methemoglobin reductase pathway


Rapoport-Lubering pathway

Embden-Meyerhof pathway

Various metabolic pathways in RBCs



Embden-Meyerhof pathway



What is it essentially?

Anerobic glycolysis

___________________________



Anaerobic glycolysis

Embden-meyerhof pathway

Embden-meyerhof pathway



Anaerobic _________

Glycolysis

Embden-meyerhof pathway



____________ glycolysis

Anerobic

Embden-meyerhof pathway



What is it essentially?

Anerobic glycolysis

Embden-meyerhof pathway



Anerobic Glycolysis


Significance

90% of energy produced through this pathway - net 2 ATP

Embden-meyerhof _________



Anaerobic _________



Significance: 90% of ENERGY produced through this _________ - net 2 ATP

pathway


glycolysis


pathway

Embden-meyerhof pathway



______ Glycolysis


Significance: 90% of _____ produced through this pathway - net 2 ____ (adenotriphosphate)

Anaerobic


energy


ATP

Embden-meyerhof pathway



Anaerobic Glycolysis



Significance: ____ of energy produced through this pathway - net 2 _____

90%


ATP

Embden-meyerhof pathway



Anaerobic _______



Significance: ______ of _____ produced through this pathway - net _ ATP

glycolysis


90%


energy


2

Embden-meyerhof pathway



___________ Glycolysis



Significance: _____ of energy ______ through this _______- ____ 2 ____

Anaerobic


90%


produced


pathay



net


ATP

Embden-meyerhof pathway



Anaerobic Glycolysis



Significance: ____ of _____ ______ ______this ______- ___________

90%


energy


produced through


pathway


net 2 ATP

Embden-meyerhof pathway



Anaerobic Glycolysis



Significance:

90% of energy produced through this pathway - net 2 ATP

Various metabolic pathways in RBCs

Embden-Meyerhof pathway


Hexose monophosphate pathway


Methemoglobin reductase pathway


Rapoport-Lubering pathway

Embden-Meyerhof pathway


___________________________


Methemoglobin reductase pathway


Rapoport-Lubering pathway

Hexose monophosphate pathway

Hexose monophosphate pathway

Produces NADPH and reduced glutathione to protect RBCs from oxidative stress

___________________________



Produces NADPH and reduced glutathione to protect RBCs from OXIDATIVE stress

Hexose monophosphate pathway

Hexose monophosphate pathway



Produces _________ and reduced GLUTHATHIONE to protect _____ from _____________ stress

NADPH


RBCs


oxidative

Hexose monophosphate pathway



Produces ________ and reduced glutha______ to protect ______ from _______ STRESS

NADPH


thione


RBCs


oxidative

Hexose monophosphate pathway



PRODUCES _________ and REDUCED glu_______ to PROTECT _____ from oxidative ______

NADPH


thathione


RBCs


stress

Hexose monophosphate pathway



___________ NADPH and ________ _______ to ___________ RBCs from ______________

Produces


reduced gluthathione


protect


oxidative stress

Hexose monophosphate pathway



______________ and _____________ to ______________ from _______________

Produces NADPH


reduced gluthathione


protect RBCs


oxidative stress

Hexose monophosphate pathway

Produces NADPH and reduced glutathione to protect RBCs from oxidative stress

Various metabolic pathways of RBCs

Embden-Meyerhof pathway


Hexose monophosphate pathway


Methemoglobin reductase pathway


Rapoport-Lubering pathway

Embden-Meyerhof pathway


Hexose monophosphate pathway


_______________________________


Rapoport-Lubering pathway

Methemoglobin reductase pathway

Methemoglobin reductase pathway



Function

Maintains heme iron in ferrous (+2) state

__________________________



Function: Maintains HEME iron in FERROUS (+2) state

Methemoglobin reductase pathway

Methemoglobin reductase pathway



Function: MAINTAINS _____ iron in _________ (+2) STATE

heme


ferrous

Methemoglobin reductase pathway



Function: ______ heme IRON in ______ (+_) ______

Maintains


ferrous


2


state

Methemoglobin reductase pathway



Function: ________ Heme _____ in _____ (__)_______

Maintains


iron


ferrous


+2


state

Methemoglobin reductase pathway



Function: ______________________ in _______________

Maintains Heme iron in ferrous (+2) state

Methemoglobin reductase pathway



Function

Maintains Heme iron in ferrous (+2) state

Various metabolic pathways of RBCs

Embden-Meyerhof pathway


Hexose monophosphate pathway


Methemoglobin reductase pathway


Rapoport-Lubering pathway

Embden-Meyerhof pathway


Hexose monophosphate pathway


Methemoglobin reductase pathway


____________________

Rapoport-Lubering pathway

Raporport-Lubering pathway



Function

Produces 2,3-DPG

________________________



Function: Produces 2,3-DPG

Raporport-Lubering pathway

Raporport-Lubering pathway



Function: Produces 2,3-_____

DPG

Raporport-Lubering pathway



Function: Produces _____-DPG

2,3

Raporport-Lubering pathway



Function: _________ 2,3-_____

Produces


DPG

Raporport-Lubering pathway



Function

Produces 2,3-DPG

Notes


Embden-Meyerhof pathway

Anaerobic pahtway of glucose metabolism



Glucose is metabolized through a series of reactions to form PYRUVATE and then LACTATE



Produces 90% of RBC energy (consumes 2 molecules of ATP, generates 4 ATP = net 2 ATP)

Embden-Meyerhof pathway



____________ pahtway of glucose metabolism



Glucose is metabolized through a series of reactions to form _________ and then __________



Produces ____ of RBC energy (consumes 2 molecules of ATP, generates _ ATP = net _ ATP)


Anaerobic


pyruvate


lactate


90%


4


2

Hexose monophosphate pathway is also known as pentose phosphate ______

shunt

Hexose monophosphate pathway



Reading

Also known as pentose phosphate shunt



Prevents accumulation of H2O2



Prevents oxidation



Reduced state is ideal

Also known as PENTOSE phosphate _____



Prevents accumulation of H2O2



Prevents OXIDATION



REDUCED state is ideal





Pathway?

shunt


Hexose monophosphate pathway

Hexose monophosphate pathway



Also known as ______ PHOSPHATE _____



Prevents ACCUMULATION of ______



Prevents ___________



__________ state is IDEAL

Pentose


shunt


H2O2


oxidation


reduced

Hexose monophosphate pathway



Also known as pentose _______shunt


Prevents _________ of H2O2


Prevents __________


Reduced state is ______

phosphate


accumulation


oxidation


ideal

Methemoglobin reductase pathway



Reading

While HMP prevents the formation of methemoglobin, this pathway reduces it if formed.

While HMP prevents the formation of METHEMOGLOBIN, this pathway REDUCES it if formed.




Pathway?

Methemoglohbin reductase pathway

Methemoglobin reductase pathway



While _____ prevents the FORMATION of ____________, this pathway ______ it if FORMED.

HMP


methemoglobin


reduces

Methemoglobin



While HMP prevents the __________of methemoglobin, this pathway _________it if __________.

formation


reduces


formed

Reading



Rapoport-Lubering pathway

Gernerates 2,3-BPG (2,3 DPG) important in oxygen delivery

Rapoport-lubering pathway



Generates ______ (_______) important in oxygen ______.

2,3 BPG


2,3 DPG


delivery

Rapoport-lubering pathway



Generates _________ important in ____ delivery

2,3 BPG/DPG


oxygen

Notes: Hexose monophosphate pathway

Detoxifies accumulated peroxide


Diverts Glucose-6-phosphate (G6P) to pentose phosphate (PP) by the action of glucose-6-phosphate dehydrogenase.



In this process, nicotinamide adenine dinucleotide phosphate (NADP) is reduced to NADPH



NADPH is then available to reduce glutathione disulfide to glutathione



Normal G6PD activity is needed for functioning RBCs



G6PD deficiency is most common RBC enzyme deficiency

Notes: Methemoglobin reductase pathway

Heme iron is constantly exposed to oxygen, an oxidizing agent



Methemoglobin results from the oxidation of heme iron from the ferrous to the ferric state



Reduction of methemoglobin by NADPH is more efficient in the presence of methemoglobin reductase.

Erythrocyte membrane


Shape of erythrocyte

Biconcave discs

Erythrocyte membrane


The shape of erythrocyte allows RBC to do what?

Pass through narrow vessels

The shape of erythrocyte allows them to pass through _____ vessels.

narrow

The shape of erythrocyte allows them to pass through __________.

Narrow vessels

The shape of _______ allows ____ to pass through narrow vessels

erythrocyte


them

Notes: Shape of erythrocyte

Biconcave discs averaging 90 fL in volume


Enables RBC to pass through narrow vessels

Reading: relative viscocity

Normal Mean cell hemoglobin concentration (MCHC) is 32-36%



MCHC above 36% compromises deformability.

What is MCHC?

mean Cell hemoglobin concentration

MCHC


Normal value

32-36%

MCHC


Above 36%



Outcome

compromises deformability

Normal Mean cell __________ concentration (MCHC) is 32-36%



MCHC above 36% __________ deformability.

hemoglobin


compromises

Normal Mean ____ hemoglobin _________ (MCHC) is 32-36%



MCHC above _____ compromises __________.

cell


concentration


36%


deformability

Normal __________cell hemoglobin concentration (MCHC) is 32-___%



MCHC _______ 36% compromises _________.

mean


36%


above


deformability

RBC membrane



Structure

Semi-permeable lipid-bilayer supported by a protein cytoskeleton

RBC membrane


structure



Semi-_________ lipid-_______ supported by a protein ________

permeable


bilayer


cytoskeleton

RBC membrane structure



______-permeable ______-bilayer ________ by a _________cytoskeleton

Semi


lipid


supported


protein

RBC Membrane structure


Semi-permeable lipid-bilayer supported by a protein cytoskeleton

Notes


Chemical composition of RBC membrane

40% lipid, 52% protein,8% carbohydrate

Define


Glycophorin

Prinicipal RBC glycoprotein, location of RBC antigens

Glycophorin



Principal RBC glyco_______, location of RBC anti____

protein


gens

Glycophorin



Principal _____ glycoprotein, location of _____antigens

RBC


RBC

Glycophorin



Principal RBC _______, location of RBC ________

glycoprotein


antigens

Glycophorin



________ RBC ________ , _________ of RBC __________

Principal


glycoprotein


location


antigens

Glycophorin


def.


Principal RBC glycoprotein, location of RBC antigens

RBC membrane structure


Recap

Semi-permeable lipid bilayer supported by protein cytoskeleton

RBC membrane structure



Semi-permeable lipid bilayer supported by protein cytoskeleton



List the protein cytoskeleton

Spectrin


Ankyrin

RBC membrane structure



Semi-permeable lipid bilayer supported by protein cytoskeleton



List the protein cytoskeleton: Spect__ and Anky___

rin


rin

RBC membrane structure



Semi-permeable lipid bilayer supported by protein cytoskeleton



List the protein cytoskeleton: ____rin and ___rin

Spec


anky

RBC membrane structure



Semi-permeable lipid bilayer supported by protein cytoskeleton



List the protein cytoskeleton

Spectrin


Ankyrin

Define


Deformability

RBCs' ability to stretch undamaged up to 2.5 times their resting diameter as they pass through narrow capilliaries and splenci pores.

_____________________



RBCs' ability to STRETCH undamaged up to 2.5 times their resting DIAMETER as they pass through narrow CAPILLARIES and splenic pores.

Deformability

Deformability



RBCs' ability to _______ UNDAMAGED up to 2.5 times their resting _________ as they pass through narrow _________ and SPLENIC pores.

stretch


diameter


capillaries

Deformability



RBCs' ability to ___________ up to ____ times their resting _________ as they pass through narrow __________ and _________ PORES.

stretch undamaged


2.5


diameter


capillaries


splenic

Deformability



RBCs' ability to _____________ up to __________ their _____________ as they pass through ____________and _____________.

stretch


2.5 times


resting diamter


narrow capillaries


splenic pores

Deformability



_____________ to stretch undamaged up to 2.5 times their resting diameter as they _____________narrow capilliaries and splenic pores.

RBC's ability


pass through

Deformability



__________ to ________________ to ________their ____________ as they ________________ and _________________.

RBC's ability


stretch undamaged up


2.5 times


resting diameter


pass through narrow capillaries


splenic pores

Deformability

RBC's ability to stretch undamaged up to 2.5 times of their resting diameter as they pass through narrow capillaires and splenic pores

Role of RBC membrane in deformability

Pass through narrow capillaries and splenic pores.



Allow aged RBC (lost deformability) to be filtered in splenic pores and destroyed by splenic macrophages.

Role of RBC membrane in ____________



Pass through NARROW capillaries and splenic PORES.



Allow AGED RBC (lost deformability) to be filtered in splenic pores and destroyed by splenic macrophages.



deformability

Role of RBC membrane in deformability



Pass through ______ capillaries and splenic ______.



Allow _____ RBC (lost DEFORMABILITY) to be filtered in splenic _____ and destroyed by splenic MACROPHAGES.


narrow


pores


aged


pores

Role of RBC membrane in deformability



Pass through narrow _________ and ______ pores.



Allow aged ____ (lost ___________ ) to be FILTERED in ______ pores and DESTROYED by ______ MACROPHAGES.


capillaries


splenic


RBCs


deformability


splenic


splenic

Role of RBC membrane in deformability



____________ narrow capillaries and splenic pores.



_______ aged RBC (lost deformability) to be _______ in splenic pores and ________ by splenic macrophages.


pass through


allow


filtered


destoryed


Role of RBC membrane in deformability



Pass through ___________ and ____________



Allow ______________ (_____________) to be ______ in ___________ and _______by ____________.


narrow capillaries


splenic pores



aged RBC


lost deformability


filtered


splenic pores


destoryed


splenic macrophages

Role of RBC membrane in deformability

Pass through narrow capillaries and splenic pores



Allow aged RBC (lost deformability) to be filtered in splenic pores


destoreyd by splenic macrophages

Can aged RBC membrane pass through splenic pores?

N

Explain how osmotic balance of the erythrocyte is maintained

The concentration of sodium is low within the cell.


The concentration of potassium is high within the cell.


Both sodium and potassium cannot pass through the membrane without cation pump.



The osmotic balance is maintained by Cation pump, which stabilize sodium concentration and fluid.

Explain how osmotic balance of the erythrocyte is maintained



The concentration of sodium is ____ within the cell.


The concentration of potassium is ____ within the cell.


Both sodium and potassium cannot pass through the membrane without ____ pump.



The osmotic balance is maintained by Cation ____, which stabilize sodium concentration and fluid.

low


high


cation


pump

Explain how osmotic balance of the erythrocyte is maintained



The concentration of sodium is _____within the cell.


The concentration of potassium is ____ within the cell.


Both _____ and ________ cannot pass through the membrane without _____________.



The osmotic balance is maintained by ___________, which stabilize _______ concentration and fluid.

low


high


soidum


potassium


cation pump


cation pump


sodium

Explain how osmotic balance of the erythrocyte is maintained



The concentration of _____ is low within the cell.


The concentration of _________is high within the cell.


Both _____ and ______ cannot pass through the ______________ without _____________



The ___________ balance is maintained by ______, which stabilize ______ concentration and ____.

sodium


potassium



sodium


potassium


membrane


cation pump



osmotic pressure


cation pump


sodium


fluid

Explain how osmotic balance of the erythrocyte is maintained



The ___________ of _______ is ____ within the ____.


The ___________ of _______ is ____ within the ____.


Both _____and __________cannot pass through the _______without ________



The ________________ is _________by __________, which __________________ and ___.



The concentration of sodium is low within the cell.


The concentration of potassium is high within the cell.


Both sodium and potassium cannot pass through the membrane without cation pump.



The osmotic balance is maintained by Cation pump, which stabilize sodium concentration and fluid.

Explain how osmotic balance of the erythrocyte is maintained

The concentration of sodium is low within the cell.


The concentration of potassium is high within the cell.


Both sodium and potassium cannot pass through the membrane without cation pump.



The osmotic balance is maintained by Cation pump, which stabilize sodium concentration and fluid.

Are sodium and potassium permebale to the RBC membrane

N

Sodium and potassium are imperemable to RBC membrane

Y

Besides sodium and potassium, what cannot pass through the RBC membrane?

Calcium

Besides _____ and _________, calcium cannot pass through the RBC membrane

sodium


potassium

Role of Calcium

Stabilize the membrane peremability



Blood clotting

Role of calcium



Stabilize the membrane _______



___________ clotting

peremability


blood

Role of calcium



__________ the _________ peremability



Blood ____________

Stabilize


membrane



clotting

Role of calcium



___________ the membrane ___________



________________

stabilize


peremability



blood clotting

Role of calcium

Stabilize the membrane peremability



Blood clotting

What is permeable to the membrane?

Water


Cl-


HCO3-

What is permeable to the membrane?



Water, ____, HCO3-

Cl-

What is permeable to the membrane?



________, Cl-, __________

Water


HCO3-

What is permeable to the membrane?

Water


Cl-


HCO3-