[DISCUSSION] MODULE 2: QUIZ 3 COVERAGE Flashcards
dynamics of RBC production and destruction
Erythrokinetics
collection of all stages of erythrocytes throughout the
body
Erythron
=the developing precursors in the bone marrow + circulating
erythrocytes in peripheral blood and vascular spaces within
specific organs
Erythron
= conveys the concept of a unified functional tissue
Erythron
= red blood cells in circulation only
Red cell mass
THE RBC MEMBRANE COMOPOSITION:
a. proteins (52%)
b. lipids (40%)
c. carbohydrates (8%)
THE RBC MEMBRANE NEEDS TO BE:
a. flexible
b. deformable
c. semi-permeable
A continually moving sea of fluid lipids that
contain a mosaic of different proteins
FLUID MOSAIC MODEL
-Some proteins float freely in the lipid stream
-others are anchored at specific parts
FLUID MOSAIC MODEL
-major source of red cell energy (90% of glycolysis)
EMBDEN-MEYERHOFF PATHWAY (EMP)
-major source of red cell energy (90% of glycolysis)
EMBDEN-MEYERHOFF PATHWAY (EMP)
glycolysis
glucose catabolism = glucose to pyruvate
pyruvate can be metabolized by:
a. Aerobic pathway: Tricarboxylic acid cycle
b. Anaerobic pathway/anaerobic glycolysis
4 RBC METABOLISM
- EMBDEN-MEYERHOFF PATHWAY (EMP)
- HEXOSE MONOPHOSPHATE PATHWAY/PENTOSE PHOSPHATE SHUNT
- METHEMOGLOBIN REDUCTASE PATHWAY
- RAPPAPORT – LEUBERING PATHWAY
contributes to 10% of glycolysis
HEXOSE MONOPHOSPHATE PATHWAY/PENTOSE PHOSPHATE SHUNT
provides adequate stores of NADPH
maintains glutathione in its reduced form
prevents denaturation of hemoglobin
HEXOSE MONOPHOSPHATE PATHWAY/PENTOSE PHOSPHATE SHUNT
Main enzyme of HEXOSE MONOPHOSPHATE PATHWAY/PENTOSE PHOSPHATE SHUNT
G-6PD
-Maintains hemoglobin iron in Fe 2+ (ferrous) to be
functional
METHEMOGLOBIN REDUCTASE PATHWAY
Responsible for the generation of 2,3-DPG which regulates hemoglobin affinity for oxygen
RAPPAPORT – LEUBERING PATHWAY
2 RBC DESTRUCTION
- EXTRAVASCULAR HEMOLYSIS / MACROPHAGE MEDIATED HEMOLYSIS
- INTRAVASCULAR HEMOLYSIS/FRAGMENTATION
happens within the RES (spleen) when complement is not
activated or incompletely activated
EXTRAVASCULAR HEMOLYSIS / MACROPHAGE MEDIATED HEMOLYSIS
90% of red cell destruction
EXTRAVASCULAR HEMOLYSIS / MACROPHAGE MEDIATED HEMOLYSIS
-increases unconjugated bilirubin, urine and fecal urobilinogen
EXTRAVASCULAR HEMOLYSIS / MACROPHAGE MEDIATED HEMOLYSIS
-seen in Rh hemolysis
EXTRAVASCULAR HEMOLYSIS / MACROPHAGE MEDIATED HEMOLYSIS
-happens within blood vessels when complement is completely
activated
INTRAVASCULAR HEMOLYSIS/FRAGMENTATION
-10% destruction
INTRAVASCULAR HEMOLYSIS/FRAGMENTATION
-leads to hemoglobinuria, decreased haptoglobin and hemopexin
INTRAVASCULAR HEMOLYSIS/FRAGMENTATION
-type of hemolysis seen in ABO hemolysis
INTRAVASCULAR HEMOLYSIS/FRAGMENTATION
2 LEUKOCYTES
a. Granulocytes
b. Agranulocytes
- share the same lineage (CFU-GEMM)
Granulocytes, red cells, monocytes, megakaryocytes
CFU-L
Lymphocytes
Production and development of the three granulocytes
GRANULOPOIESIS
three granulocytes:
N, E, B
GRANULOPOIESIS Similarities:
Maturation sequence
GRANULOPOIESIS Differences:
Cytokines that influence their production and
differentiation
NEUTROPHIL DEVELOPMENT
Stem cell pool:
Pluripotential Hematopoietic Stem Cell
NEUTROPHIL DEVELOPMENT Mitotic pool:
Progenitors
Precursors
common myeloid progenitor
. CFU-GEMM
(granulocyte-macrophage progenitor)
CFU-GM
(granulocyte progenitor)
CFU-G
Neutrophils Mitotic pool:
Progenitors
a. CFU-GEMM (common myeloid progenitor)
b. CFU-GM (granulocyte-macrophage progenitor)
c. CFU-G (granulocyte progenitor)
NEUTROPHIL
Mitotic pool:
Precursors
a. Myeloblast
b. Promyelocyte
c. Myelocyte
NEUTROPHIL DEVELOPMENT
Maturation pool:
Precursors
Metamyelocyte
Neutrophilic band
NEUTROPHIL Maturation pool:
Precursors
a. Metamyelocyte
b. Neutrophilic band
Size (um) 14-20
N:C Ratio 8:1 – 4:1
Nucleus Shape Round to oval
Nucleus Chromatin Homogenous, delicate, fine euchromatin
Nucleus Nucleoli 2-4
Cytoplasm Staining Slightly basophilic
Cytoplasm Granules No granules
Cellular activity 0-3% of nucleated cells in the BM
Classification:
-Type I blasts
“granular blasts”
-Type II blasts
-Type III blasts
MYELOBLAST
Size (um) 16-25
N:C Ratio 3:1 – 2:1
Nucleus Shape Round to oval
Nucleus Chromatin Heterochromatin slightly coarse
Nucleus Nucleoli 1-3
Cytoplasm Staining Basophilic
Cytoplasm Granules Formation of Primary or Azurophilic granules
Cellular activity 1-5% BM Hof/Paranuclear halo surrounding the nucleus
PROMYELOCYTE
Size (um) 12-18
N:C Ratio 1:1
Nucleus Shape Oval or round
Nucleus Chromatin Coarser and condensed
Nucleus Nucleoli None
Cytoplasm Staining Mixture of acidophilic and basophilic
Cytoplasm Granules Formation of Secondary/ Specific granules “Dawn of neutrophilia”
Cellular activity
6-17%
Last stage capable
of mitosis
MYELOCYTE “DAWN OF NEUTROPHILIA”
Size (um) 15-18
N:C Ratio 1:1
Nucleus Shape Kidney shaped
Nucleus Chromatin Coarse and clumped
Nucleus Nucleoli None
Cytoplasm Staining Beige or salmon
Cytoplasm Granules Formation of Tertiary / gelatinase granules
Cellular activity 3-20% in the BM
METAMYELOCYTE
Size (um) 9-15
N:C Ratio 1:1 to 2:2
Nucleus Shape Elongate/band (C or S)
Nucleus Chromatin Coarse and clumped
Nucleus Nucleoli None
Cytoplasm Staining Beige or salmon
Cytoplasm Granules
-Continuous formation of Tertiary / gelatinase granules
-Formation of secretory granules (vesicles)
Cellular activity No answer given
STAB
Size (um) 9-15
N:C Ratio 1:1 to 2:2
Nucleus Shape 2-5 lobes
Nucleus Chromatin Highly condensed chromatin
Nucleus Nucleoli None
Cytoplasm Staining and Cytoplasm Granules
- conatian continuously forming pink to rose-violet secretory granules
Cellular activity No answer given
NEUTROPHIL / POLYMORPHONUCLEAR
(PMN) CELLS
3 NEUTROPHIL FUNCTION
- PHAGOCYTOSIS
- GENERATION OF NETs: NEUTROPHIL EXTRACELLULAR TRAPS
- Secretory function
GENERATION OF NETs
Nuclear and organelle membrane dissolves – DNA release
DNA + cytoplasmic enzymes – cell membrane rupture – NET release
Extracellular thread-like structures believed to represent chains of
nucleosomes from DNA
GENERATION OF NETs: NEUTROPHIL EXTRACELLULAR TRAPS
Have enzymes for neutrophil granules
NETs: NEUTROPHIL EXTRACELLULAR TRAPS
Neutrophil Secretory functions
a. Transcobalamin I/R binder (needed for vitamin B12 absorption)
b. Variety of cytokines
Kill gram positive gram negative bacteria and fungi
NETs: NEUTROPHIL EXTRACELLULAR TRAPS
EOSINOPHIL DEVELOPMENT
Maturation sequence
Stem cell:
Pluripotent hematopoietic stem cell
EOSINOPHIL DEVELOPMENT
Maturation sequence
Progenitors:
a. CFU-GEMM (common myeloid
progenitor)
b. CFU-Eo
EOSINOPHIL DEVELOPMENT
Maturation sequence
Precursors:
a. Myeloblast
b. Promyelocyte
c. Myelocyte
d. Metamyelocyte
e. Eosinophilic band Eosinophil
Not fully characterized
EOSINOPHILIC MYELOBLAST
Cytochemical identification only
PROMYELOCYTES
Charcot-Leyden crystal protein
Primary granule PROMYELOCYTES
similar to neutrophil myelocytes
MYELOCYTES
Large, pale, reddish-orange
Secondary granule MYELOCYTES
resemble neutrophil counterpart
METAMYELOCYTES and BAND FORM
-Formation of secretory granules/vesicles
METAMYELOCYTES and BAND FORM
METAMYELOCYTES and BAND FORM
2 other organelles present:
Lipid bodies, small lysosomal granules
Size: 9-15um
Nucleus: bilobed
Granules: refractile, orange-red granules (involved in allergic and
parasitic infections
EOSINOPHIL
4 EOSINOPHIL FUNCTION
- DEGRANULATION
- Regulation of Immune responses
- Indicator of parasitic infection
- Hallmark of allergic disorders
-granules move to plasma mem – fuse with cell mem – empty contents to
ECF
Classical exocytosis
-Granules fuse together with eosinophils – fuses with cell mem – empty
contents
Compound exocytosis
-secretory vesicles remove spp CHONs from secondary granules – secretory
vesicles migrate to plasma mem – empty to ECF
Piecemeal degranulation
-delete double-positive thymocytes
Regulation of Immune responses
-act as Ag presenting cells
Regulation of Immune responses
-promote proliferation of effector T cells
Regulation of Immune responses
-Initiate type 1 or type 2 immune response
Regulation of Immune responses
-Regulate mast cells
Regulation of Immune responses
-MBP and Eosinophil cationic protein destroys tissue-invading helminths and
prevents reinfection
Indicator of parasitic infection
Hallmark of allergic disorders
-concentration = severity of disease
(airway inflammation, mucosal cell damage)
Hallmark of allergic disorders
-Secrete HISTAMINASE, IL-5
function for airway remodelling
Hallmark of allergic disorders
-Secrete eosinophil-derived fibrogenic growth factors
BASOPHIL DEVELOPMENT
Stem cell pool
Maturation sequence
I. Pluripotential hematopoietic stem cell
II. Progenitors
a. CFU-GEMM (CMP)
b. CFU-Baso
III. Immature Basophil
IV. Mature Basophil
BASOPHIL DEVELOPMENT
Maturation sequence: Progenitors:
a. CFU-GEMM (CMP)
b. CFU-Baso
Formed throughout remaining maturation stages
BASOPHIL GRANULES Secondary Granules
BASOPHILIC Secondary Granules Contain:
• Histamine
• Platelet-activating factor
• Leukotriene C4 • Interleukin-4 • Interleukin-13
• Vascular endothelial growth factor A
• Vascular endothelial growth factor B
• Chondroitin sulfates (e.g. Heparin)
Possess unsegmented or bilobed nucleus with condensed chromatin.
Blue-black water soluble granules almost obscure the nuclear material of the cell.
BASOPHILS
FUNCTIONS: Allergic or hypersensitivity reaction
BASOPHILS
-Possess surface IgE receptors
BASOPHILS
-Regulate T helper2 response (Il-4 and IL-3)
BASOPHILS
-Induce B cells to synthesize IgE
BASOPHILS
-Mediate allergic responses (prod of HISTAMINE, granzymes B, retinoic acid)
BASOPHILS
-Promote angiogenesis (vascular endothelial growth factor production)
BASOPHILS
MONOPOIESIS Maturation sequence:
I. Pluripotential hematopoietic stem cell
II. Progenitors
III. Precursors
IV. Monocyte
V. Macrophage (T)
MONOPOIESIS
Progenitors:
a. CFU-GEMM
b. CFU-GM
c. CFU-M
MONOPOIESIS Precursors:
a. Monoblast
b. Promonocyte
-Large cells (40-50 microns)
MACROPHAGES
-Oval reticulated chromatin nucleus and a pale, frequently
vacuolated cytoplasm
MACROPHAGES
-Either wandering or fixed as to location
MACROPHAGES
PROMONOCYTE POOL:
NO STORAGE POOL:
Pools in circ:
Half life:
NV:
Relative:
Absolute:
6 x 8 8 cells/kg
-Produces 7 x 10 6 monocytes / kg per hour
Monocytes are immediately released
Circulating and marginal (marginal more numerous)
2-11%
0.1 – 1.3 x 10 9/L
-Function for innate immunity
MONOCYTE/MACROPHAGE
-Perform phagocytosis via toll-like receptors and Fc receptors and are
involved in inflammatory responses
MONOCYTE/MACROPHAGE
-Produce nitric oxide – cytotoxic against viruses, bact, fungi, protozoa,
helminths, tumor cells
MONOCYTE/MACROPHAGE
-Removes debris and dead cells
MONOCYTE/MACROPHAGE
-Maintenance of iron storage pool and synthesis of a wide variety of
proteins
MONOCYTE/MACROPHAGE
LYMPHOCYTES
Functionally classified into 3
- T lymphocytes
- B lymphocytes
- Null lymphocytes
cellular-mediated immunity: attacking foreign antigens directly
60-80%, lasts 4-10 years
T lymphocytes
humoral-mediated immunity: produce antibodies
2-%, lasts 3-4 years
B lymphocytes
tumor – host defense
10%
Null lymphocytes
Are not end cells: Resting
-When stimulated, will undergo mitosis to produce both memory and effector cells
LYMPHOCYTES
Reticulate from the blood to the tissues and back to the blood
LYMPHOCYTES
are capable of arranging antigen receptor gene segments to produce a wide variety of antibodies and surface receptors
B and T lymphocytes
originate in the BM
develop and mature outside of the BM
Early lymphocyte progenitors
T and NK lymphocytes
Making the lymphocyte kinetics extremely complicated and not well
understood
LYMPHOCYTES
AG independent
(Central/primary lymphoid organs)
BM, Thymus
AG dependent
(Secondary lymphoid organs)
Spleen, lymph nodes, tonsils, MALT, Peyer’s patches
-@ these stages where immunoglobulin gene rearrangement occurs
BM – pro-B – pre-B – immature B cell
produces a unique immunoglobulin antigen receptor
B lymphocytes
-leave BM to migrate to secondary lymphoid organs – take up
specific zones (e.g lymph node follicles)
IMMATURE B CELL/HEMATOGENE
-Develop initially in the Thymus
T lymphocytes
-Lymphoid progenitors migrate from the BM to the thymic cortex
T lymphocytes
-under the regulation of cytokines produced by thymic endothelial
cells, they progress to stages known as pro-T, pre-T and immature T cells
T lymphocytes
-Undergo antigen receptor gene rearrangement to produce T cell
receptors that are unique to each T cell
T lymphocytes
T lymphocytes 2 categories:
CD4+ or CD8+
(further apoptosis of self-reactive T cells occur)
Immature T cells - Thymic medulla
take up residence in specific zones – paracortical areas
secondary lymphoid organs
(?) eventually come in contact with antigen = cell activation = memory cells, effector
T cells, both
*T cells in secondary lymphoid organs or in circulating blood
are cells that morphologically resemble monocytes
Atypical, reactive or plasmacytoid lymphocytes
(?) of the cytoplasm by adjacent red cells = RL
(?) cytoplasm = RL, blue-grey color = M
(?) that give monocytes a typical
“ground glass appearance of the cytoplasm
-Sharp indentation
-Increased amount of dark blue
- lack many fine granules
heterogenous group of cells with respect to their surface
antigens CD 56, CD 16, CD 3-, CD7 large granular lymphocytes
NK cells
azurophilic granules that are peroxidase negative
cytoplasm LYMPHOCYTES
Essential for antibody production
LYMPHOCYTES B cells
Antigen presentation to T cells
LYMPHOCYTES B cells
Produce cytokines that regulate a variety of T cell and antigen
presenting functions
LYMPHOCYTES B cells
mediate immune responses against intracellular pathogens
CD4 effector lymphocytes: Th1:
mediate host defense against extracellular parasites
CD4 effector lymphocytes: Th2:
immune responses against extracellular bacteria and fungi
maintaining self-tolerance by
regulating immune responses
CD4 effector lymphocytes: Th17
Treg (CD4+CD25+ regulatory T)
-Capable of killing target cells by secreting granules containing
granzyme and perforin
T cells:
CD8 effector lymphocytes
-Activating apoptotic pathways in the target cell
T cells:
CD8 effector lymphocytes
-Cytotoxic T lymphocytes
T cells:
CD8 effector lymphocytes
-Innate immunity
T cells:
NK lymphocytes
-capable of killing certain tumor cells and virus-infected cells without
prior sensitization
T cells:
NK lymphocytes
-Modulate functions of other cells (macrophages and T cells)
T cells:
NK lymphocytes
Size (um): 12-20
N:C ratio: 4:1 to 3:1
Nucleus Shape: Round to oval
Chromatin: Delicate
Nucleoli: 1-2
Cytoplasm Staining: Basophilic
Cytoplasm Granules: No Granules
Cellular Activity
Carries out 2 mitotic divisions in 60 hours to produce 8 monocytes
Can carry out 4 mitotic divisions in 60 hours under increased demand
MONOBLAST
Size (um): 12-18
N:C ratio: 3:1 to 2:1
Nucleus Shape: Slightly indented or folded
Chromatin: Delicate
Nucleoli: > 1
Cytoplasm Staining: Blue-gray
Cytoplasm Granules: Formation of AZUROPHILIC GRANULES
Cellular Activity
Carries out 2 mitotic divisions in 60 hours to produce 8 monocytes
Can carry out 4 mitotic divisions in 60 hours under increased demand
PROMONOCYTE
LARGEST CELL IN PERIPHERAL BLOOD
MONOCYTE
Size (um): 15-20
N:C ratio: 2:1 to 1:1
Nucleus Shape: Oval or round KIDNEY/ HORSE-SHOE May be folded, showing brain-like convolutions
Chromatin: Looser (Lace-like/ Stringy
Nucleoli: NONE
Cytoplasm Staining: Blue-gray
Cytoplasm Granules: Many fine azurophilic granules having GROUNDGLASS APPEARANCE (frosted)
Cellular Activity
Enter tissues and mature to macrophages
MONOCYTE
Cell Size (microns):
10-18
Nucleus:
Coarse chromatin
Round or oval
With 1-2 nucleoli
Cytoplasm:
No granules present
Appears smooth
Moderate to dark blue
LYMPHOBLAST
Cell Size (microns):
Maybe same size as lymphoblast or smaller
Nucleus:
More clumped chromatin
Round or oval in shape
With 1- 2 nucleoli
Cytoplasm:
Usually nongranular
Moderate to dark blue
PROLYMPHOCYTE
MATURE LYMPHOCYTE
SMALL LYMPHOCYTE
MEDIUM LYMPHOCYTE
LARGE LYMPHOCYTE (Atypical Lymphocyte)
Cell Size (microns):
Nucleus:
Cytoplasm:
SMALL LYMPHOCYTE
Cell Size (microns):
Nucleus:
Cytoplasm:
MEDIUM LYMPHOCYTE
Cell Size (microns):
Nucleus:
Cytoplasm:
LARGE LYMPHOCYTE
(Atypical Lymphocyte)
