Week 2 of CPR 1- Blood and inflammation
what is the *life span of RBC's*?
*120 days*
what is the *normal range of platelets in blood*?
*120-300 thousand*
what is the *normal range of erythrocytes/RBC's in blood*?
*4.2 - 6.2 million* (which is why RBC's make up about 99% of cells within the blood)
what is the *normal range of leukocytes/WBC's in blood*?
*5-10 thousand*
what is the *key component of RBC's*? and why?
*Hemoglobin* -bc hemoglobin is the thing that actually attaches to oxygen and carbon dioxide for the RBC to be able to transport them also has surface proteins/antigens- A, B, and Rh
what is *hematocrit*? how is the hematocrit determined?
*Percentage of the total blood volume that are erythrocytes* -put blood in a tube, and put the tube in a centrifuge to spin the tube. -the RBC's settle to the bottom. -the percentage of blood that is RBC's in the bottom of the tube = the hematocrit
what is the function of the *Neutrophils*? what percentage do they make up of all WBC's? are they granulocytes or Argranulocytes?
*fastest responder of all leukocytes to bacteria. Role: phagocytosis of bacteria via release of lysozymes, defensin proteins, strong oxidants* 60-70% (majority; last about 3-5 days) -granulocyte, polymorphonuclear leukocytes (PMN) -nucleus has 2-4 lobes (young have horseshoe shape) - cytoplasm contains fine, invisible granules and azurophilic granules -Surface receptors exhibited: Fc Receptors, complement receptors, scavenger receptors, and toll-like receptors
what is the function of the *Lymphocytes*? what percentage do they make up of all WBC's? are they granulocytes or Argranulocytes?
*immunological function* (B & T cells) 20-25% nucleus is dark, oval to round cytoplasm is a thin, pale blue rim around the nucleus can be found in blood as well as lymph -agranulocyte
if a patient presents w/ a fever d/t a bacterial infection, what cellular count would most likely be elevated? and why?
*neutrophil count* would be elevated -neutrophils destroy bacteria
what is the function of the *Monocytes*? what percentage do they make up of all WBC's? are they granulocytes or Argranulocytes?
*phagocytic (produce cytokines)* >> called macrophages when they enter connective tissue -takes longer to arrive but comes in large numbers -acts as antigen-presenting cell -phagocytosis of bacteria, dead cells and tissue debris - forms giant cells at sites of chronic infection 3-8% 3 day lifespan nucleus appears indented (kidney shaped) cytoplasm is foamy gray (contains azurophilic granules) Largest WBC called Histiocyte in CT, alveolar macrophages (dust cells) in lungs, and Kupffer cells in liver -agranulocyte
what are *thrombocytes*?
*platelets* has a lifespan of 5-9 days platelets removed by macrophages fixed in the spleen and liver contains: - alpha granules: clotting factors that cause prolif of vascular endothelial cells, smooth muscle and fibroblasts for vessel repair - dense granules: ADP, ATP, Ca2+, serotonin, fibrin-stabilizing factor, and enzymes that produce thromboxane A2
what is *sickle cell* caused by?
*single point mutation in β globin gene: changes glutamic acid >> valine* at the 6th amino acid position -causes shape to be sickled
in an average individual, *what is the total blood volume*? of this, *what is the total RBC/erythrocyte volume* (hematocrit)?
*total blood >> 5.5 L (6 quarts)* *total RBC >> 2.5 L* (45% of the total blood volume = .45 x 5.5 = 2.5L)
what is the *shape of RBC's*? what is the function of RBC's?
-*biconcave* which maximizes the SA and allows a flexible shape for narrow passages -*transporter of the oxygen and carbon dioxide* (via attachment to hemoglobin)
what is the *normal hematocrit level for women vs. men*?
-*women >> 42%* -*men >> 48%* (Percentage of the total blood volume that are erythrocytes)
What's the function of the stem cell niche/endosteal niche?
1) storage of quiescent stem cells 2) self renewal 3) inhibition of differentiation
What is the main function of vascular niche?
1) support and promote the differentiation and maturation of progenitors into formed elements of blood 2) secretion of growth factors by stromal cells
Where does hematopoiesis occur in the different stages of embryonic and adult life?
1) yolk- sac phase- hematopoiesis starts in 3rd week of gestation... formation of "blood islands" 2) hepatic phase- major blood forming organ in the 2nd trimester 3) Bone marrow phase- begins during 2nd trimester (involves other lymphatic tissues) After birth: 4) hematopoiesis occurs only in the bone marrow
what are the *2 groups of Leukocytes/WBC's in the blood?* what type of WBC's belong in each group?
1. *Granulocytes* ("grand ben") -basophils -eosinophils -neutrophils 2. *Agranulocytes* ("AML") -monocytes -lymphocytes (T cells & B cells)
what are the *5 types of Leukocytes/WBC's in the blood?* and what are the percentages of WBC's that each type makes up?
1. *Neutrophils* >> 60-70% *increases with acute bacterial infection 2. *Lymphocytes* >> 20-25% *increases with chronic infection or cancer 3. *Monocytes* >> 3-8% *increases with fungal or viral infection 4. *Eosinophils* >>2-4% *increases with parasitic infection 5. *Basophils* >> .5-1% *increases with allergic reaction
what are the *3 main components of blood*?
1. *Plasma* 55% (water, proteins, solutes) 45% Cells: 2. *Erythrocytes* 99% (RBC's) 3. *Buffy coat* <1% (platelets & WBC's/leukocytes)
what are the *2 components of the blood buffy coat*?
1. *Platelets* 2. *Leukocytes/WBC's*
what are the *3 components of blood plasma*? and what percentages does each component make up of the plasma?
1. *water >> 92%* 2. *proteins >> 7%* (albumin, globulins, fibrinogen, regulatory proteins) 3. *other solutes >> 1%* (electrolytes, nutrients, respiratory gases, waste products)
Which mediators are responsible for chemotaxis, leukocyte recruitment and activation?
1. Cytokines (TNF and IL-1) 2. chemokines 3. C3a and C5a 4. Leukotrienes 5. bacterial products and peptides
What are the different lymphocytes and their functions?
1. T Cells - differentiate in the thymus - cell-mediated immunity - long life-span - attack viruses, fungi, transplanted organs, cancer cells, and some bacteria 2. B cells - production of antibodies - destroy bacteria and other toxins - turn into plasma cells that produce antibodies - variable lifespan 3. Natural Killer cells - attack many different microbes and tumor cells - destroy foreign invaders by direct attack
What are the 2 components of inflammation?
1. Vascular reaction 2. Cellular (leukocyte) reaction
What mediators are responsible for a pain response?
1. bradykinin 2. prostaglandin
What occurs in lymphopoiesis?
1. colony forming units (CFU)for respective B and T cells 2. lymphoblasts: large, undifferentiated cells 3. prolymphocytes: medium-sized cells, condensing chromatin, no cell surface antigens 4. some migrate from bone marrow to thymus, divide and differentiate to T cells 5. other remain in bone marrow and differentiate into B cells which then migrate to lymph tissues
What are the precursors/steps in thrombopoiesis?
1. controlled by thrombopoietin (TPO) 2. megakaryoblast: endomitosis, polyploid (~32 N) 3. megakaryocyte: large multi-lobed nucleus 4. platelets are formed from fragments of megakaryocyte cytoplasm 5. platelet demarcation channels
What mediators are involved in fever respons?
1. cytokines (IL-1 and TNF) 2. prostaglandins
What are the organs of the lymphatic system?
1. diffuse lymphatic tissue 2. lymphatic nodules 3. lymph nodes 4. spleen 5. bone marrow 6. thymus
What are the 2 kinds of giant cells?
1. foreign body giant cells (typical of non-immunological agents): nuclei become centrally grouped 2. langhan's giant cells (typical of immunologic agents): nuclei arranged in horseshoe
What mediators are responsible for increased vascular permeability?
1. histamine 2. serotonin 3. bradykinin 4. leukotrienes
Which mediators have a role in tissue damage?
1. leukocyte lysosomal enzymes 2. reactive oxygen species 3. nitric oxide
What are the precursors of monocytopoiesis?
1. monoblasts: large, undifferentiated cells 2. promonocytes: kidney-shaped nucleus, azurophilic granules 3. monocytes: "sky" blue cytoplasm, kidney-shaped nucleus 4. enter the circulation, proceed to tissue spaces, differentiate into macrophages
What are the precursors in granulopoiesis?
1. myeloblasts (common precursor): no granules, cytoplasmic blebs 2. promyelocyte: large nucleus, azurophilic granules Neutrophilic, Eosinophilic, or Basophilic: 3. myelocyte: condensed rounded nucleus, *specific granules* 4. metamyelocyte: kidney shaped nucleus, specific granules 5. band (stab): C-shaped nucleus, specific granules 6. mature form: neutrophils, eosinophils, or basophils (neutrophils>eosinophils>basophils) process takes about 11 days
What are the events in neutrophil migration?
1. neutrophils express cell-cell recognition molecules 2. neutrophils are slowed down by selectin receptor on endothelial cells 3. neutrophils roll on surface with endothelial secretions, which induces neutrophils to express integrins 4. Integrin binds I-CAM1 to promote adhesion to endothelium 5. Neutrophil extends pseudopod between the endothelial cells 6. neutrophil exits circulation and enters CT (migration is mediated by cytokines)`
What are the subdivisions of chronic inflammation?
1. non-specific - arises following an episode of acute inflammation when the prev response was not adequate 2. specific a. non-granulomatous b. granulomatous: presence of granulomas (giant cells) and epithelioid macrophages and multinucleated giant cells
What are the cells of the lymphoid system?
1. principal effector cells: - B cells - T cells - NK cells 2. Support cells: - monocytes - macrophages - neutrophils - basophils - eosinophils -dendritic cells - follicular dendritic cells 3. Specialized epithelial and stromal cells: - reticular cells - Langerhans - epithelioreticular cells
What are the precursors in erythropoiesis?
1. proerythroblast: no Hgb, large nucleus, and basophilic cytoplasm 2. basophilic erythroblast: some Hgb, condensing nucleus 3. polychromatophilic erythroblast: "muddy" cytoplasm 4. orthochromatophilic erythroblast: increased Hgb 5. reticulocyte: no nucleus, some ribosomes, 6. erythrocyte: only Hgb, no ribosomes
Which mediators are vasodilators?
1. prostaglandins 2. nitric oxide 3. histamine
What is the function of lymphatic system?
1. removal of excessive interstitial fluid 2. fatty acid absorption and transport of fat and chyle to general circulation 3. basis for self-defense- distinguish self from non-self - carried out by cells, effector molecules, tissues and organs
What are 4 main outcomes of acute inflammation?
1. resolution- damage was neutralized and tissue damage was minimal 2. healing by fibrosis- damage neutralized with tissue destruction then organization through phagocytosis and granulation tissue formation 3. abscess formation- marked neutrophilic response with tissue destruction 4. progression to chronic inflammation- persisting famagin agent with tissue destruction, organization with continued inflammation
What are 3 components of acute inflammation
1. vascular dilation -relaxation of vascular smooth muscle results in engorgement of tissue with blood (hyperemia) 2. endothelial activation -increased endothelial permeability which allows leakage of plasma proteins (edema) -expression of adhesion molecules - production of factors that cause vascular dilation 3. neutrophil activation and migration - increased expression of adhesion molecules - increased motility - increased capacity for bacterial killing
What are the 2 categories of inflammation?
Acute - rapid onset, short duration, 5 cardinal signs, and neutrophil migration Chronic -could follow acute inflammation if stimulus persists -may be an insidious low-grade response without acute reaction -long duration -macrophages, lymphocytes, prolif of blood vessels, fibrosis, and tissue destruction
What comes from CFU-E? CFU-Meg? CFU-GM?
All colony forming units come from myeloid stem cells CFU-E is the progenitor cell for erythrocytes and first differentiates into precursor, proerythroblast CFU-Meg is the progenitor cell for platelets and first turns into Megakaryoblast (precursor) CFU-GM is the progenitor cell for granulocytes and macrophages and first turns into either a myeloblast (for NKs) or monoblast as the precursor
What are different kinds of myelopoiesis?
Erythropoiesis -formation of erythrocytes Granulocytopoiesis -formation of granulocytes Monocytopoiesis -formation of monocytes Thrombopoiesis -formation of thrombocytes
What is fibrinous inflammation?
Exudate in fibrinous inflammation has high plasma protein content (fibrinogen is converted to fibrin and deposited in tissues) associated with serous membrane-lined cavities (pleural, pericardial and peritoneal) fibrin strands form a mat, often causing adhesion between adjacent surfaces
What is the stem cell niche (endosteal niche)?
Hematopoietic stem cells reside in the cavity of long and axial bones, surrounded by stroma, which is made of cells derived from mesenchymal stem cells (which give rise to fibroblasts, adipocytes, endothelial cells, and osteoblasts) defined as "a spatial structure in which HSCs are housed and maintained by allowing self-renewal in the absence of differentiation
What is the progenitor cell for lymphocytes?
Lymphoid stem cell
What is the structure of bone marrow?
Made of reticular fibers (type III collagen), veins, arteries, sinusoids, and islands of cells red marrow: active hematopoiesis yellow marrow: fat, capillaries, reticular cells, and inactive hematopoiesis
what is the function of the *Basophils*? what percentage do they make up of all WBC's? are they granulocytes or Argranulocytes?
Modulates the *immune response and inflammation (histamine)* Releases: - heparin as anticoagulant - histamine for vasodilation - leukotrienes for prolonged pulmonary smooth muscle constriction - interleukin 4 and 13 to promote synthesis of IgE <1% (smallest group of WBC's; last a few hours-days) nucleus is irregular, s-shaped, bilobed nuclei cytoplasm is large, variable-sized granules specific granules with heparin (sulfates)-->basophilia, histamine, and leukotrienes (IL-4 and IL-13) -granulocyte
What gives rise to erythrocytes?
Proerythroblasts five rise to immature RBC (reticulocytes) that become erythrocytes once in circulation
What is the action and source of kinins (ie bradykinin)?
Source - plasma (made in liver) action: -increased vascular permeability -smooth muscle contraction -vasodilation -pain
What is the source and action of nitric oxide?
Source -*endothelium* -macrophages Actions: -vascular smooth muscel relaxation -vasodilation -killing of microbes
What is the source and actions of chemokines?
Source: -leukocytes -activated macrophages Actions: -chemotaxis -leukocyte activation
What is the source and actions of cytokines (TNF and IL-1)?
Source: -macrophages -endothelial cells -mast cells Actions: -local endothelial activation -expression of adhesion molecules -fever -pain
What is hte source and action of leukotrienes?
Source: -mast cells -leukocytes Action: -increased vascular permeability -chemotaxis -leukocyte adhesion and activation
What is the source and action of prostaglandins?
Source: -mast cells -leukocytes Actions: -vasodilation -pain -fever
What is the source and action of complement products (C5a and C3a)?
Source: plasma (produced in liver) Action: -leukocyte chemotaxis and activation -vasodilation
What is the action and source of serotonin?
Source: platelets Actions: -vasodilation -increased vascular permeability
What is the action of histamine and its source?
Source: -mast cells -basophils -platelets actions: - vasodilation -increased vascular permeability -endothelial activation
What are the immunological agents leading to granulomatosis?
Syphilis and yaws (Treponema) infective organisms that grow within cells (viruses) hypersensitivity reactions (extrinsic allergic alveolitis) autoimmune conditions (SLE) infections by fungi, protozoa, and parasites
What is thalassemia?
This is a hereditary hypochromic anemia that results from decreased alpha or beta chains (depends on if B-thalassemia or A-thalassemia) which is then compensated by an overproduction of the other chain. this lead to red blood cell membranes binding and could lead to toxic aggregates
What is the difference between totipotent, pluripotent, multipotent, and unipotent?
Totipotent- ability to differentiate into all tissues (found in embryonic tissue and extra-embryonic tissue aka placenta, amnion, and chorion) Pluripotent- ability to develop into all cells and tissues of the body (>210 differentiated adult cell types) Multipotent- ability to develop into few cell types Unipotent- ability to develop into only a single cell type
What is anisocytosis?
a blood abnormality where RBCs are of unequal sizes can be detected by peripheral smears can signify conditions like anemia and thalassemia
What is suppurative inflammation?
aka purulent exudate pus is semi-liquid containing neutrophils, fluid and necrotic tissue abscess is a circumscribed collection of pus
What is pyogenic bacteria and what are some examples?
bacteria that promot purulent inflammation 1. staphylococci 2. streptococci which can lead to 1. lobar pneumonia 2. bronchopneuomina 3. acute appendicitis
What do neural stem cells differentiate into
blood cells skeletal muscle cells
what do bone marrow stromal cells differentiate into?
cardiac muscle cells skeletal muscle cells
What is hereditary spherocytosis?
caused by variety molecular defects in the genes that code for spectrin, ankyrin, band 3 and band 4 proteins--> responsible for shape of erythrocyte defect in these proteins-->spherical shape instead of biconcave
What is a pluripotent stem cell?
cells that have the capacity to develop into many different types of cells
What is a granuloma?
cellular attempt to contain a persistent agent that's been difficult to eradicate characterized by presence of activated epithelioid macrophages and multinucleated giant cells
Which chemical mediators attract neutrophils to the site of tissue damage?
complement component C5a and LTB4
What is opsonization?
complement proteins "flag" the microorganism for phagocytosis.
What occurs in resolution outcome of acute inflammation and what are some examples?
complete restitution of normal tissue architeture and function (can only occur when the CT framework is intact and the tissue has capacity to regenerate) neutrophils and necrotic tissue are removed by phagocytosis (macrophages) which leave the tissue via lymphatic drainage Ex: - following pneumonia, re-growth of alveolar lining cells depends on resident stem cells to divide and differentiate -recovering from sunburn
What does hematopoietic stems cells first differentiate into?
either common myeloid progenitor (CMP) cells or common lymphoid progenitor (CLP) cells
What occurs in erythropoiesis?
erythrocyte formation occurs in adult red bone marrow of certain bones the main stimulus for erythropoiesis is *hypoxia* erythropoietin is produced by kidney
What is lymphopoiesis?
formation of lymphocytes
What occurs in sickle cell anemia?
genetic defect in hemoglobin molecule where hydrophilic glutamic acid is replaced by hydrophobic Val
What are the hematopoietic growth factors?
growth factors regulate proliferation and maturation found progenitor cells have surface receptors for specific cytokines and growth factors (glycoproteins) to bind and cause a response 1. *erythropoietin (EPO)* is produced by the kidneys and increases erythrocyte precursors 2. *thrombopoietin (TPO)* is a hormone from the liver that stimulates thrombocyte formation 3. *cytokines* are local hormones of bone marrow that stimulate proliferation in other marrow cells or produces CSF and interleukins to stimulate leukocyte productions Side note: hematopoietic cells will die unless exposed to growth factors
What are the 5 cardinal signs?
heat aka calor (mediated by hyperemia), redness aka rubor (mediated by hyperemia), swelling aka tumor (hyperemia and fluid exudation), pain aka dolor (PGE2 and bradykinin release), loss of function aka functio laesa(combined effects, swelling and pain)
what is the function of the *Eosinophils*? what percentage do they make up of all WBC's? are they granulocytes or Argranulocytes?
important for allergic reactions & *killing parasitic worms* -MBP, ECP, and EPO imparts cytotoxic effect -releases histaminase to neutralize histamine -arylsulfatase neutralizes leukotrienes -internalizes antibody-antigen complexes 2-4% (last 8-12 days) nucleus is bilobed cytoplasm contains large, uniform sized granules (stain orange-red with acidic dyes) contain 4 proteins: 1) Major basic protein (MBP) that imparts acidophilia to cells, 2) eosinophilic cationic protein, 3) eosinophil peroxidase, 4) eosinophil derived neurotoxin -granulocyte
What is a hematopoietic stem cell?
in bone marrow, this gives rise to multiple colonies of progenitor stem cells
Where is the the endosteal niche found?
in epiphyseal areas or spongy bone stem cells are closely associated with osteoblasts
What is serous inflammation?
main tissue response is accumulation of fluid with a low plasma protein and cell content (transudate) serious inflammation can be seen in skin in response to burn and in serious membrane-lined cavities
What do hematopoietic stem cells differentiate into?
neurons and glial cells skeletal muscle cells cardiac muscle cells liver cells
What are lymphocytes?
non terminally differentiated cells immunosurveillance 60-80% are long lived and go on to become T cells 30% are short lived, immature, or activated bu destined for specific tissue
What occurs in healing by fibrosis outcome of acute inflammation?
occurs with substantial damage to connective tissue framework and/or in tissues that lack ability to regenerate specialized cells necrotic debris and acute inflammatory exudate are first removed by macrophages defect gets filled by granulation tissue (this is called organization) granulation tissue gets replaced by collagen forming a fibrous scar
What are the features of chronic inflammation?
ongoing tissue damage chronic inflammatory infiltrate 1. macrophages 2. lymphocytes 3. plasma cells 4. eosinophils, mast cells, and fibroblasts fibrosis
where do *platelets/thrombocytes originate from*?
originate in bone marrow as *megakaryoblasts* which become *megakaryocytes*, whose cytoplasmic fragments become platelets -assist in *blood clotting*
what is the *difference between plasma vs. serum*?
plasma >> *serum + (fibrinogen & clotting proteins)* serum >> *plasma - (fibrinogen & clotting proteins)*
What is poikilocytosis?
poikilocytes are RBCs of distorted shape when these cells make up 10% or more of total population it is known as poikilocytosis
what is the *function of Hemoglobin*? how does this occur (based off of its structure)?
protein that *binds oxygen and carbon dioxide to the RBC* (to be transported) -hemoglobin consists of: 2 global chains, 4 irons, & 4 hemes (porphyrin) -each heme is attached to each iron, and carries one molecule of oxygen -Each hemoglobin can carry 4 oxygen molecules
What is the vascular niche?
quiescent HSCs detach from the endosteal niche and migrate to the center of the bone marrow into the vascular zone from where they establish hematopoiesis this is where endothelial cells, fibroblasts, and adipocytes are found works along with endosteal niche to balance HSCs between quiescence, self-renewing activity, and production of early progenitors
*What is blood*?
specialized connective tissue where the matrix consists of free-flowing ground substance (plasma) without fibers all blood cell types originate in the connective tissue of bone marrow
What is thrombocyte function?
surveillance of blood vessels blood clot formation (hemostasis) to plug ruptured areas platelets pull on fibrin threads--> clot retraction trapped platelets release factor XIII, which stabilizes the fibrin threads edges of vessel are pulled together fibroblasts and endothelial cells repair
What are the non-immunological agents inducing granuloma chronic inflammation?
suture material wood/vegetable matter metal or glass splinters inorganic materials like silica and beryllium
What occurs in abscess formation as an outcome for acute inflammation?
this is a localized collection of pus followed by extensive tissue damage and pyogenic bacteria May be either: acute abscess- expansion limited by organization and repair and margin of abscess chronic abscess- abscess may get encapsulated by granulation and fibrous tissue (walled off) May become chronic inflammation if large number of virulent bacteria, organization/repair gets overwhelmed, or if expansion of abscess and tissue damage
What is the difference between transudate and exudate?
transudate: protein content <25 g/L exudate: protein content >25 g/L
