Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Hematology > Lecture 6 > Flashcards

Lecture 6 Flashcards

1
Q

what are Erythrocytes

A
  • Anucleate cells when mature
  • Comprised of 95% hemoglobin
  • Function
    ‒Primary carry O2 from lungs to tissues
    ‒Secondary – return CO2 from tissues to lungs and buffer pH of blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What does Normal Erythropoiesis look like

A
  • Mature RBCs circulate for 120
    days
  • BM always over-produces RBCs:
    ‒Excess precursors ready for quick
    response if needed
    ‒‘Unnecessary’ RBC precursors die by ‘programmed cell death’ or
    apoptosis (natural process) if no stimulus occurs
  • 1% RBCs replaced daily
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are the

*Progenitors and
precursor cells?

*Controlled by?

*Maturation
sequence?

of Erythropoiesis

A

-the process of how RBCs are produced in the bone marrow in erythroid island next to the venus sinusoid or around a central macrophage with Iron
start with the common myeloid progenitor - megakaryocyte erythrocyte progenitor - mature in the perpherial blood after release

-controlled by EPO - main hormone to control Bone marrow production of red cells - growth factor cytokine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Erythropoietin (EPO) what is it

A
  • Glycoprotein hormone (or growth factor)
  • Synthesized mainly in the kidneys (some in liver)
  • Released into the bloodstream in response to hypoxia
    ‒E.g., not enough RBC or abnormal RBCs, defective HGB, or poor lung function
  • Peritubular cells (fibroblasts) in kidney detect insufficient O2 this triggers EPO production mediated by increased EPO gene transcription by Hypoxia Inducible Factors (HIFs)

HIF proteins build up and promote erythropoiesis

in low PO2 , HIF proteins promote activation of genes that can adapt to hypoxia conditions. HIF binds to kidney and increases EPO and increases O2 in blood by increasing RBC production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Erythropoietin (EPO) what does it do

A
  • stimulate and regulate the production of erythrocytes
  • Binds to EPO-receptors on RBC progenitors and precursors causing:
    1. Allows early release of immature RBCs (reticulocytes) from BM
    2. Preventing RBC apoptosis (CFU-E progenitors protected)
    3. Reduce BM transit time (shortens time between and reduces the number of mitoses of precursors)
  • Recombinant version available for use in treating anemia
    ‒ Especially due to renal disease (no EPO)
    ‒ Used by athletes in ‘doping’ scandals

when epo binds to its receptor EPOR and stimulates JAK2 pathway to promote RBC production at a faster rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Nomenclature for Erythroid
Precursors

A

Pronormoblast
Basophilic normoblast
Polychromatic (or Polychromatophilic) normoblast
Orthochromic normoblast
All above nucleated precursors found ONLY in the bone marrow

Reticulocyte- no nuc- in BM then PB
Erythrocyte - slowly loses nucleus as it matures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does Erythropoiesis occur

A

CFU-GEMM acts on the HSC forming the BFU-E: Burst-Forming Unit-Erythroid - produces daughter cells with few EPO receptors with the help of EPO form CFU -E

colonies CFU-E: Colony-Forming Unit Erythroid have many EPO receptors allowing for their differentiation of the below precursors

Pronormoblasts:
* Earliest recognizable erythrocyteprecursor in the BM
* Production stimulated by EPO
* Able to divide
* Each daughter cell matures to the next stage

Basophilic & Polychromatic Normoblasts:
* Able to divide
* Each daughter cell matures to the next stage

Orthochromatic normoblast:
* Does not divide (nucleated)
* Matures to a Reticulocyte in BM then to PB (no nucleus)

Mature Erythrocyte:
* 18-21 days from BFU-E to RBC
* 8-32 RBCs produced from 1 pronormoblast

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Typical Production of
Erythrocytes

A
  • 1 Pronormoblast produces 8 RBCs
  • Last division at Polychromatic
    normoblast stage
  • Lose nucleus in BM, released to PB before complete maturation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Criteria for differentiating the
stages of RBC development:

A

A - Cell size decreases, and cytoplasm turns blue to salmon pink
B- Nucleus size decreases and color changes from purplish-red to dark blue – N:C Ratio decreases
C - Nuclear chromatin becomes coarser, clumped & condensed (pyknotic) and nucleoli disappear
D- Composite of changes during developmental process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

RBC Maturation Chart:

A

18-24 days= mature RBC from BFU E for 1 week and one week as a CFU E and 1 week to mature from the pronormoblast to mature RBC.

cell diameter and DNA reduces as cell matures

what happens the RBC as the DNA/RNA content reduce and increased acidophilia occurs in a Wrights stain?
RBC cytoplasm from blue to pink increases in hemoglobin content.
Basophilia is high in the prophase - high DNA/RNA/Protein content.

Green arrow increase in Hemoglobin or eosinophile staining. Acidophila corresponds with RBC maturation
hemoglobin makes up most of the protein in the later stages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

HEMOGLOBIN BIOSYNTHESIS

A

-made in mitochondria and cytoplasm
-65% of Hemoglobin Synthesis
occurs in nucleated stages-
-35% Hgb synthesis occurs in the
Reticulocytes

Why can’t mature RBCs make hemoglobin? Mature RBCs lack nucleus, mitochondria, and other organelles, and are therefore, incapable of protein synthesis
The immature forms have these cell tools to make hemoglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Orthochromic Normoblast

How does cell lose its nucleus?

A
  • Nucleus is condensed or ‘pyknotic’ meaning the cell cant divide. Losing the nuc will mean that the RBC will be able to carry more hemoglobin
  • Membrane ‘projection’ forms as nucleus squeezes out to edge of cell
  • Entire projection pinches off and nucleus is ejected
  • Bone marrow macrophages engulf and breakdown expelled nucleus
  • This stage is often seen in PB during disease states
    ‒ Rarely are earlier stages seen except in very severe disease
  • We call this a ‘Nucleated RBC’ or NRBC if seen in PB
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Polychromatic Erythrocyte
(Reticulocyte) - after nucleus is lost

A
  • Large, oval or irregularly-shaped (lumpy) cell with no nucleus
  • Still producing hemoglobin- through RNA and Ribosomes that are leftover in the cytoplasm
  • Cytoplasm contains precipitated RNA (seen supravitally)
  • Location
    ‒ In BM for ~ 1 to 2 days
    ‒ In PB for ~ 1 day then mature into Erythrocytes
  • Up to 2.5% of PB RBC are ‘Retics’ – this is normal
    ‒ > 2.5% in PB is reported as ‘Increased Polychromasia’ - disease process - Wrights GIemsa with methylene blue azure

the polychromatic erythrocyte is retained in the spleen for polishing by splenic macrophages, which
results in the biconcave discoid mature RBC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Mature Erythrocyte

A

Biconcave disc- shape is good for hemoglobin are close to the RBC membrane
* Central pale area- Central pallor 1/3 of cell diameter~
‒ Corresponds to concavity

  • Unable to synthesize HGB
    ‒ No nucleus, ribosomes or mitochondria, no protein synthesis
  • Carries oxygen from lungs to tissues and exchanges O2 for CO2
  • Recall, mature RBC lives ~ 120 days
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Three aspects of RBC physiology
are crucial for normal erythrocyte
maturation, survival and function:

A
  1. RBC membrane‒ Deformability depends on
    membrane shape, viscosity, and elasticity
  2. Hemoglobin structure and function
  3. Cellular energetics

RBCs job is gas exchange using hemoglobin and biconcave shape

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

RBC Membrane contains:

A
  • to maintain shape stable membrane structure
  • transport of nutrients, ions, etc.
  • Considered a lipid-bilayer tied to an cytoskeleton
    ‒ Phospholipids (fluidity) and cholesterol (tensile strength) in equal parts elasticity and strength

Separating plasma from cytoplasm
* Maintain an osmotic differential
* Permeable to H2O, bicarbonate and chloride (anions)
* Impermeable to Ca2+, K+, and Na+ (cations)
‒ Passive transportation of anions, gases, water and glucose
‒ Active transportation of cations

17
Q

RBC Membrane Deformability

A

*RBCs must squeeze through capillaries to exchange O2 & CO2
*Depends on RBC SHAPE, VISCOSITY, & MEMBRANE
ELASTICITY
*Biconcave SHAPE better than sphere – more surface area

18
Q

Cytoplasm Viscosity

A
  • Refers to concentration of HGB in RBC cytoplasm
  • We measure:
    ‒ Amount of HGB (g/L) in total blood
    ‒ By weight per RBC- MCH (pg)
    ‒ Concentration of HGB per RBC – MCHC (g/L) – Normal 32-36%
  • Low viscosity allows the RBC to deform and squeeze through narrow spaces
  • RBCs with MCHC >36% are too viscous & less deformable = RBC life span ↓
    ‒ Cells become damaged as they pass through narrow capillaries or small splenic pores - cold agglutination or spherocytes
19
Q

RBC Membrane part Membrane Carbohydrates

A
  • glyco- protein and -lipid chains
  • Function in cell-cell recognition and adhesions (such as, ABH blood)
  • anchor protective coating called Glycocalyx
    ‒ Adsorbs substances from extracellular matrix
    ‒ Gives net negative charge to RBC membrane
    -RBCs able to repel one another
20
Q

MEMBRANE CHARGE & ZETA
POTENTIAL

A
  • Negative charges of membrane keep RBCs apart – stops them from
    ‘bunching’ up in circulation
  • Anything that will reduce the Zeta potential will allow RBCs to come
    closer together

-the negative charge of RBC is produced by high salic acid content on the membrane

-the positive charge form an ionic cloud around the negatively charged cells

-the difference in the neg and positive is the zeta potential

21
Q

RBC Membrane * Transmembrane Proteins –

A

function as transport and adhesion sites, surface antigens, and signaling receptors ‒ Rh Blood group system, cation pumps (Na/K-ATPase and Ca2+ ATPase), Aquaporin 1, Glut-1, etc.

‒ Possible immunogenicity to
proteins that act as ‘antigens’

  • Anchor to underlying cytoskeleton (Ankyrin or Actin junctional complex) which Provide vertical membrane structure and stability helps with integrity and prevent membrane loss
22
Q

RBC Membrane * Cytoskeletal Proteins

A

*complex lattice and/or anchorage structure found on inner (cytoplasmic) lipid bilayer ‒ Major proteins are α- and β-spectrin, Ankyrin, Protein 4.1, Protein 4.2,Tropomodulin, Tropomyosin, -
-do not penetrate the bilayer

‒ Provides horizontal or lateral support to RBC
membrane and Gives mechanical stability and supports membrane elasticity

23
Q

what are Spectrins

A
  • form a hexagonal cytoskeletal lattice on inner lipid bilayer
    (they are antiparallel heterodimers)
  • Ends linked to actin junctional complex
  • Bonds break and form to RBC membrane deformability
  • Loss or mutations of these proteins can affect the membrane integrity and eventually the shape of the RBC
24
Q

What is
Hemoglobin?

A
  • Globular protein
  • Consists of- 4 Globin chains
    and 4 Heme groups
25
Q

What are Globin Chains

A
  • Protein - long chains of amino acids or polypeptides
  • 141-146 amino acids per chain
  • Different amino acid sequences = different types of globin chains
  • Each combination of two types results in a different HGB
    -* Most types of HGB have: ‒ 2 α ‒ 2 others to form molecule
  • chain divided into 8 helices and 7 nonhelical segments
  • Combine to hold the HEMO
26
Q

What is HEME?

A

-Protoporphyrin IX (C, H, N ring structure)
+ 1 central atom of Ferrous iron
(Fe2+)

Each HEME component can combine
reversibly with 1 molecule of oxygen

27
Q

Iron Sources & Forms

A
  • Ingested and absorbed in GI tract as Fe2+ or Ferrous iron
  • Stored mainly in liver as:
    ‒Ferritin
  • Fe3+ or Ferric Iron is stored in Apoferritin (cage-like protein)

‒Hemosiderin
* Partially degraded aggregates of Ferritin

  • Iron transported to BM as Transferrin
    ‒Up to two molecules bind to Apotransferrin
    (glycoprotein)
  • RBC precursors have receptors to Transferrin
    When bound, receptors and Transferrin are taken into cell & Ferric ions released into cytoplasm
28
Q

HEMOGLOBIN
ASSEMBLY

A

-synthesis occurs in the BM
-production involves enzymes working in the mitochondria and cytoplasm of the RBC

  • globin chains proteins produced from gene transcription in nucleus of RBC and translation to polypeptide chains on ribosomes in the RBC cytoplasm
  • Dimers of: 1 α /HEME & 1 non-α /HEME combine to form tetramer (positively charged)
29
Q

Normal Hemoglobins

A
  • Fetus – Hb F - high affinity for O2
  • Newborn – mostly Hb F, switching to Hb A
  • Adult – mostly Hb A, small amount of Hb A2, very little Hb F

KNOW THE CHART *** WITH STARS

can use Electrophoresis to see what is needed

30
Q

Hemoglobin
Function

A
  • Carries and releases Oxygen
    to tissues
    ‒ Each HGB tetramer can bind
    4 O2 molecules
  • Facilitates removal of CO2
  • Buffers pH of blood (by binding and releasing hydrogen ions)
  • Transports nitric oxide (regulator of vascular patency)
31
Q

RBC Metabolism

A
  • Energy not required to exchange oxygen/carbon dioxide (passive)
  • Energy is required for RBCs metabolic processes
  • RBCs can’t produce enzymes – lack nucleus,
    ribosomes, and mitochondria

** Rely on glucose from plasma and a series of enzyme pathways for ATP production
‒Anaerobic glycolysis (main) - Embden-Meyerhof Pathway (entry via facilitated diffusion)

‒Glycolysis Diversion Shunts-Oxidative glycolysis –
* Hexose Monophosphate Pathway
* Methemoglobin Reductase Pathway
* Rapoport-Luebering Pathway

32
Q

RBC Senescence

A

RBC getting old

  • To maintain membrane volume, permeability, shape, and flexibility, RBCs rely on glucose from plasma and enzyme pathways for ATP - limited time
  • Mature RBCs ⇒ no nucleus, no ribosomes or mitochondria, ↓ ATP over time
    ‒ ∴ as the cellular functions decline the cell is unable to repair cell structure or replenish enzymes involved in metabolic pathways/metabolic function
  • ‘Old’ RBCs change over 120-day lifespan: ‒Membrane becomes rigid and fragile – membrane loses deformability
    ‒Selective permeability decreases, cells more permeable to water – spheroid shape results

RBCs are taken out via intra or extravascular hemolysis

33
Q

RBC Destruction

A
  • Spleen- filters large circulating blood volume ‒ Movement through spleen is slow, glucose depletes, and glycolysis slows, less ATP is produced, and pH is low increasing oxidation of iron
  • Stressful environment + age-related changes, leaves ‘Old’ RBCs unable to squeeze through splenic sinusoids and are removed by splenic Macrophages
  • This is called Extravascular Hemolysis
  • Most RBCs lost this way
    ‒ AKA Macrophage-Mediated Hemolysis
    ‒ Occurs outside of vasculature
    ‒ Excessive in some Hemolytic anemias
34
Q

Extravascular Hemolysis

A

In spleen, senescent RBCs are phagocytosed and lysed by Macrophages
* Enzymes of the macrophage phagolysosome either salvage or metabolize RBC
* HGB is broken down & components are released
‒ Globin into metabolic amino acid pool
‒ Iron stored as Ferritin in macrophage or released as Transferrin in plasma
‒Protoporphyrin degraded eventually into Bilirubin and then Bile or Urobilinogen

35
Q

Intravascular Hemolysis

A
  • RBC destruction inside the blood vessels ‒AKA Fragmentation or Mechanical Hemolysis
    ‒ mechanical or traumatic stress in vessels
    ‒Damage to blood vessels that causes clots to trap the RBCs
  • RBCs fragment or lyse
    ‒Free hemoglobin released directly into the peripheral blood
  • Minor component of normal RBC destruction
  • System in place to salvage RBC components
  • Free HGB in plasma attaches to transport proteins Haptoglobin or if oxidizedbinds to Hemopexin
  • Breakdown products taken to liver &/or excreted through kidney
36
Q

In times of Increased
Intravascular Hemolysis what happens

A

‒ Kidney can become overwhelmed & renal failure can occur (hemoglobinemia
and hemoglobinuria can be seen)
‒ E.g., Malarial protozoa bursting out of RBCs

37
Q

Feedback loop

A

-after 120 days damaged RBC removed via extravascular hemolysis via spleen or liver
-Fe recycled and globin sent to amino pool causing decrease of O2
-This decrease causes production of EPO in kidney
-Which bind to surface receptors of erythrocyte progenitors to stimulate Bone marrow erythropoiesis
-This stimulates the CFU-E and then after 7 days when precursor cells mature to produce a fully goblinized RBC
- The rbc is released in to peripheral circulation to be use for gas exchange

Hematology (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions