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BLISS > Histology Of Blood And Hemopoiesis > Flashcards

Histology Of Blood And Hemopoiesis Flashcards

1
Q

Composition of blood

A

55% plasma

44% RBCs

1% “Buffy coat” (white blood cells and platelets )

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2
Q

Difference between plasma and serum

A

Serum =. Blood that has gone through the coagulation (clot) process.
-contains special growth factors and other proteins released by platelets when clotted

Plasma = blood that has not gone through the coagulation process

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3
Q

Red blood cell characteristics

A

Any clear with NO mitochondria

Lack membrane-bound organelles

contain numerous hemoglobin molecules (4 different globin peptide chains with 1 iron molecule per globin peptide chain)

  • primary function is to transfer oxygen and carbon dioxide throughout the body via binding to hemoglobin (oxygen) and globin (carbon dioxide)
  • Oxygen (heme) and carbon dioxide (globin chains) do not compete for the same location. *
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4
Q

Plasmalemma

A

Cell membrane of RBCs

Have peripheral and integral membranes which both function to anchor and organize the cytoskeletal proteins

possess blood type antigens on the extraceullar surface which determine your blood type.

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5
Q

Platelets

A

Membrane-bound cell fragments released by megakaryocytes that are anuclear with sparse mitochondria and possess a glycocalyx extracellular membrane.

Contains 3 types of granules

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6
Q

2 major categories of platelet granules and the specific names.

A

Alpha: PDGF, PF-4

Delta: Serotonin, ADP/ATP

Degranulation occurs rapidly when platelets adhere to collagen of endothelial cells and causes a rapid increase of cytoplasmic calcium

also has glycogen granules

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7
Q

What two intracellular structures serve to help rapid depolarization and release of granules from platelets?

A

Marginal bundles and open canalicular systems

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8
Q

Clotting steps (general)

A

Primary aggregation: glycocalyx of platelets allow platelets to adhere to the damage site and form a platelet plug

Secondary aggregation: platelets that’s re already clotted together release specific adhesive glycoproteins and ADP which promotes clotting of platelet group aggregation

Blood coagulation: proteins released from the damaged site and PGF4 promote sequential interaction of plasma protiens and other clotting activities. Forms a 3D network of fibers trapping RBCs and platelets to from the clot itself

Clot retraction: clot retraction occurs when clot contracts due to platelet-derived actin and myosin interactions

Clot removal: clot is removed by proteolytic enzyme plasmin released by the interaction of plasminogen and macrophage interaction from endothelium

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9
Q

Leukocyte general actions

A

Immune response (innate and acquired)

Allergic response (basophils and mast cells)

Inflammatory response

Repair of tissues (macrophages)

Destroy invaders

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10
Q

Neutrophils

A

Polymorphic nucleus with 3-5 lobes (looks like “stepping stones”)

Azurophilic (granules stains dark)

Contains lysozyme, defense’s and myeloperoxidase granules

Have lots of glycogen stores and few mitochondria

Function as first line of defense against most infections (mainly bacterial)

Activiely track and pursue bacteria throughout body

most common granulocyte

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11
Q

Eosinophils

A

Bi-lobed nucleus: “ on ear headphones”

Azurophilic staining and granules stain pink and red

Contains MBPs, peroxidase

Functions to modulates inflammatory responses (especially due to allergies)

Primary function is to stop parasitic infections!

granulocyte

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12
Q

Basophils

A

Bi-lobed or S-shaped nucleus (usually cant see it though and covers majority of cell)

Azurophilic granules present (stains dark purple all around cell)

Contains heparin, GAGs, histamines, PAF

Functions to mediates inflammation and is involved in allergic reactions and type 1 hypersensitivity from binding to IgE

granulocyte

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13
Q

Lymphocytes

A

smallest WBC

Contains spherical nucleus with thin ring of basophilic cytoplasm around it (approximately 70% of cell has dark purple stain, rest is light purple)

Functions to become T/B and NK cells based on their CD markers

agranulocyte

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14
Q

Monocytes

A

Indented of C-shaped nucleus with azurophilic granule staining

Functions to give rise to macrophages, osteoclasts, microglia and other mononuclear phagocyte system cells.

Agranulocyte

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15
Q

Steps of leukocyte extravasion

A

1) local activated macrophages release proinflammatory cytokines (IL-1 and TNF-a) that signal to endothelial cells to upregulated selections (P-selectin)
2) passing neutrophils bind to these selections and allow it to loosely “roll” along the endothelial cells
3) leukocytes that are “rolling” upregulate integrins on the leukocytes and integrin ligand (ICAM-1) on the endothelial cells and down regulates junctional complexes (gap junctions)
4) integrins and selectins bind and allow leukocytes to receive further stimulation and become sensative to chemokines
5) leukocytes become motile and follow chemokines and squeeze between endothelial cells via diapedesis to get to the site of infection/damage

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16
Q

Main sites of hemopoiesis with respect to age

A

1-3 months in gestation (1st trimester)= yolk sac

3-6 months in gestation (2nd trimester)= liver and spleen (more liver)

8months to birth(3rd trimester) = all bones via bone marrow

Birth - 29 years = all bones but primarily tibia, femur, sternum, vertebrae and ribs

30- 100 years of age = sternum, vertebrae and rib bone marrow

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17
Q

Hematopoietic cords and sinusoidal capillaries

A

Cords = Sites of proliferation and maturation of hematopoietic cell lines into cell lineages

Capillaries = allows for passage of mature blood cells into the blood stream via a pressure gradient

Both found in red bone marrow

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18
Q

Hemopoeitic stem cell differentiation

A

Pluripotent stem cells located in bone marrow that differentiates based on what cytokines they are exposed to during maturation

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19
Q

Equation used to estimate normal Cellularity

A

100% - patient age +/- 10%

Ex: 30 year old = 60-80% normal range

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20
Q

Erythropoiesis

A

Differentiation of pro-erythroblasts from MEP or CEP via erythropoietin (EPO) expression

Proerythroblast nucleus increases mRNA production and increases polyribosomes which in turn will slowly become hemoglobin

Overtime, mRNA is reduced and the nucleus condenses while hemoglobin content increases inversely. (basophilic and polychromatophilic erythroblasts)
- during this process, the cell stains less basophilic (purple) and more eosinophilic (Pink) overtime

Eventually releases nucleus (pyknotic nucleus) and forms a reticulocyte (immature RBC)

Reticulocytes are pushed into sinusoidal capillaries and become mature RBCs

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21
Q

Thrombopoiesis

A

Differentiation of megakaryoblast from MEP or CEP via thrombopoietin (TPO) presence.

Multiple rounds of endomitosis (DNA division, but not cellular division, results in multiple nuclei but only 1 cell) in a megakaryoblast differentiate it into a megakaryocyte.

Megakaryocytes are extended into sinusoidal capillaries which releases tips (platelets) into the blood stream directly

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22
Q

Granulopoiesis

A

Differentiation of a granulocyte progenitor cell and myeloblast driven by GM-CSF and G-CSF and specific growth factors which commit them to specific granulocyte.

Starts as myeloblast (basophilic standing cytoplasm cell with no granules)

Then becomes promyelocyte (possessing a well defined golgi and RER, also contains granules and stains more basophilic)

Then becomes myelocyte/ metamyelocyte (first signs of differentiation of granulocytes where they gain specific granules and accumulate in the cytoplasm) until this stage, it is impossible to distinguish between the 3 granulocytes
Last stage of mitotic division

Then becomes mature definitive granulocyte after its nucleus has condensed into polymorphic shape

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23
Q

Primary lymphoid organs vs secondary lymphoid organs

A

1st: Red bone marrow. And thymus
2nd: Mucosa-associated lymphoid tissue (MALT), lymph nodes and spleen

Difference is 1st = site of maturation and 2nd = site of activation

24
Q

Lymphatic tissue histologically

A

Supported by reticular tissue (except for thymus)

  • contains reticular cells and fibers (type 3 collagen fibers)
  • contains T and B cells and plasma cells
  • also contains macrophages, dendritic cells and APCs
25
Q

Where does positive selection/ tolerance occur in the thymus?

A

The cortex

26
Q

Negative and positive selection of T cells in thymus

A

Positive selection: lymphocyte survives if it binds to the MHC complexes (cortex)

Negative selection: lymphocyte survives if it does not bind to self antigens
(Medulla)

27
Q

Final step of maturation in the thymus

A

2% of total naive lymphocytes survive positive and negative selection

  • undergo selective loss of either CD4 or CD8 expression which officially gives the T-cell its properties
28
Q

MALT

A

Found throughout the mucosa in the UG and GI and respiratory system

  • usually found in the lamina propria sections of the tissue
  • contain lymphoid nodules which are localized concentrations of lymphatic tissue that contain mostly T and B cells. (Can be primary or secondary)
29
Q

Primary vs secondary nodules in MALT

A

Primary nodule: not active immune response, support cells
-stains darker

Secondary nodule: active immune response is initiated via APC cell infiltration

  • causes differentiation into germinal center (B-cells) and mantle zone (T-cells)
  • stains lighter than primary when active

Histologically, primary looks the same color throughout, whereas secondary has a clear germinal center in the middle

30
Q

Lymph nodes

A

Capsules with trabeculae and contain 3 sites:

Cortex: outside and contain subcapsular sinuses and lymphoid nodules
-sites of immune response

Paracortex: does not contain lymphoid nodules and instead contain HEVs
- brings in APCs and active lymphocytes

Medulla: contains T cells in the medullary sinuses and medullary cords

31
Q

Sites of entering the lymph nodes

A

90% = blood stream via HEVs

10% = lymph stream via afferent vessels

All stuff migrates to lymphoid nodules of the cortex, which is the site of an immune response

32
Q

Spleen functions

A

Filtering the effete RBCs

Site of immune responses

Reservoir for blood and blood cells

Site of fetal hemopoiesis

33
Q

Splenic pulp

A

20% = white pulp
- contain PALS, transient lymphoid nodules and central arterioles. Site of immune response

80% = red pulp
- contains penicillar arterioles, splenic sinuses, splenic cords. Site of blood filtration

34
Q

Albumin

A

Most abundant plasma protein

  • made in liver
  • serves primarily to maintain osmotic pressure of blood and to bind drug components to move throughout body
35
Q

Alpha and beta globulins

A

Include transferrin, fibronectin, prothrombin and other coagulation factors

  • also include lipoproteins
  • made in liver primarily
36
Q

Immunoglobulins

A

Secreted by plasma cells as antibodies or y-globulins

37
Q

Fibrinogen

A

Largest plasma protein and is made in liver

- during clotting, polymerizes as insoluble, cross-linked fibers of fibrin that block blood loss from small vessels

38
Q

Complement proteins

A

Innate immune system defense that is found in the plasma of blood.

39
Q

Blood functions

A

Transfer of respiratory gases bound to hemoglobin

Moves hormones and regulatory proteins

Moves immune cells nutrients and metabolites

Moves wastes products

Maintains homeostatic regulation
- osmotic balance, acid-base balance and body temp

Clotting and healing of vasculature

40
Q

Plasma composition

A

92% water

7% plasma protiens

1% other solutes

  • wastes
  • minerals/electrolytes
  • nutrients
  • dissolved gases
41
Q

Peripheral membrane proteins in plasmalemma

A

Band 4.1 and ankyrin

  • interact with other proteins such as spectrin to from structural support
42
Q

Integral plasmalemma proteins

A

Band 3 and glycoproteins

proteins that serve as anchors under the protein complexes formed by the peripheral membrane proteins

  • serve together with peripheral proteins to increase structural integrity and produce the biconcave disc shape. Also increase flexibility since the interacts between peripheral and integral membrane proteins can be rearranged
43
Q

What are progenitor cells called?

A

Colony-forming units (CFUs)

44
Q

Yellow vs red bone marrow

A

Red bone marrow = site of hemopoiesis

Yellow bone marrow = adipocyte filled marrow that is arrested
- site of nutrients storage and promoting bone growth

  • as you get older, red gradually changes to yellow.
  • some can be reverted back to red in times of hypoxia and/or severe bleeding*
45
Q

Band cell

A

Intermediate stage of neutrophils granulocytes prior to complete maturation

  • marked by elonged nucleus but not yet polymorphic.
  • can enter blood stream and continue to mature
46
Q

4 compartments of neutrophils

A

Granulopoetic compartment: found in active red marrow and move when needed

Storage compartment: mature cells that remain in the marrow and not move

Circulating population: mature and band neutrophils that are within the blood stream

Marginating population: cells that adhere loosely and accumulate transiently on the endothelial surface of venules and small veins.
- dont undergo diapedesis

47
Q

Functions of blood

A

Transport and distribution

Homeostatic regulation

Clotting and healing of vasculature

48
Q

Plasmalemma proteins

A

Ankyrin proteins: bind to integral proteins

Spectrins: give stability/flexibility and biconcave shape to the RBC

band dimers: integral proteins in RBCs

49
Q

Common myeloid progenitor cell types (CMP)

A

Erythrocytes

Megakaryocytes: Platelets

Both myeloblast and monoblasts

myeloblast cells:

  • eosinophils
  • leukocytes
  • basophils/mast cells

Monoblast cells:

  • microglia
  • osteoblasts
  • macrophages
50
Q

Common lymphoid progenitor cell types (CLP)

A

Lymphocytes

  • B cells
  • T cells
  • NK cells
51
Q

Marginating cells

A

Neutrophils that bind to endothelium but dont extravate into tissues, they just hang onto the endothelium until they are needed
(NOT CIRCULATING)

51
Q

Monocytopoiesis

A

Differentiation of a CMP progenitor cell into a monocyte via M-CSF

Promonocyte: first stage and is completely indistinguishable from a pro granulocyte
- basophilic staining and “dented” nucleus

Monocyte: nucleus is C-shaped with azurophilic granules accumulation
- can be distinguished from granulocytes

51
Q

Maturation sites of lymphocytes

A

Immature T cells: thymus

Immature B cells: bone marrow

Immature NK cells: bone marrow and secondary lymphoid organs

52
Q

Difference between dendritic cells and follicular dendritic cells

A

DCs = not found in lymphoid tissues and do not currently possess antigens

FDCs = found in lymphoid tissues and present antigens for B cells

53
Q

Types of cortex thymus epithelium

A

Type 1: squamous between capsule and cortex
- isolate cortical compartments and contribute to creating the blood-thymus barrier. Prevent unregulated exposure

Type 2: stellate
- support macrophages and lymphocytes and act as APCs for maturation of T cells and present MHC for positive tolerance/selection

Type 3: squamous between cortex and medulla
- create barrier between cortex an medulla as well as present MHC for positive tolerance/selection

54
Q

Types of medulla thymus epithelium

A

Type 4: similar to type 3 in cortex

Type 5: support maturing T-cells and present self-antigens for negative selection

Type 6: “hassall corpuscles” that regulate local DC activity and development of regulatory T cells by secreting cytokines

BLISS (42 decks)

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