ICL 1.1: Blood & Hematopoiesis Flashcards
what are the functions of the blood?
- respiration: transporting oxygen and CO2 between lungs and tissues
- nutrition: transport of absorbed food materials
- excretion: transport of metabolic waste to kidneys, lungs, skin and intestines for removal
- maintenance of the normal acid-base balance
- regulation of water balance through effects of blood on the exchange of water between the circulation fluid and the tissue fluid
- regulation of body temperature by distribution of body heat
- defense against infection by WBC and antibodies
- transport of hormones and regulation of metabolism
- transport of metabolites
- coagulation
what are the three components of blood when you centrifuge blood?
- plasma (top)
- buffy coat
- RBC (bottom)
what are the components of the plasma layer of blood?
- water (93%)
- proteins: albumins, globulins, fibrinogen, regulatory proteins
- other: electrolytes, nutrients, gases, waste, hormones
nutrients: glucose, AA, lipids, cholesterol, vitamins
waste: urea, creatinine, bilirubin
what is in the buffy coat of blood?
- platelets (120-300 thousand/mmˆ3)
2. leukocytes: neutrophils, lymphocytes, monocytes, eosinophils, basophils
what is in the RBC layer of blood?
RBCs lol
this is the hematocrit! it’s 40% of the spun volume
what’s the difference between Hb and hematocrit?
Hgb = amount of Hb protein (g/dL)
Hct = packed cell volume (volume of RBCs/volume blood)
what is plasma?
basically everything
plasma = serum + fibrinogen and other clotting proteins
anti-coagulated blood is spun in centrifuge to separate cells from plasma
what is serum?
serum = plasma - fibrinogen - clotting proteins
blood is allowed to clot, separating serum from clotting proteins and cells
serum is what we get metabolic panels from like figuring out somebody’s electrolyte levels!
what proteins are in plasma?
- albumins
- globulins
- clotting factors
- complement proteins
- lipoproteins
what do you do if someone has a deficiency of multiple coagulation factors?
give them a transfusion of fresh frozen plasma (FPP) to replace clotting factors!
what is warfarin?
aka Coumadin - used as anticoagulant
when someone ODs on these medications you can give them FPP to replace clotting factors
what is the total protein made of?
mostly albumin and gamma globulins
it’s the TP of the plasma proteins
what do high or low total protein levels signify?
high TP = hypergammaglobulinemia
can get serum protein electrophoresis (SPEP) to separate out proteins and see which ones are elevated
low TP = liver failure or malnutrition
What is the source and function of albumen?
Liver
Maintains colloid osmotic pressure
Protein transport
What is the source and function of alpha and beta globulin?
Liver
Transport
What is the source and function of gamma globulin?
Plasma cells
Make up antibodies for immunity/defense
What is the source and function of clotting factors
Liver
Coagulation
What is the source and function of complement proteins?
Liver
Microorganism destruction
Inflammation
What is the source and function of lipoproteins?
Liver
Lipid transport
What are the common components of stains?
Eosin: acidic, red/pink (stains cytoplasmic components)
Methylene blue: basic (stains acidic components like nucleic acids)
Azure: stains cytoplasmic granules containing proteins and proteoglycans
What’s the average WBC concentration?
5-10,000/mm^3
What’s the average lifespan of a WBC?
5 days in circulation
A few hours once they’re extravascular in the tissues
What’s the average concentration of RBCs?
4.6-6.2 million/mm^3
What’s the average concentration of platelets in the blood?
150-400 thousand/mm^3
What’s the lifespan of a platelet?
14 days
When does hematopoiesis start?
Prenatally!
Starts 2 weeks after conception in the yolk sac
Then the liver starts making RBCs around 6 weeks followed by the liver (second trimester)
Then bone marrow makes RBC in 3rd trimester and throughout life
What is a compensatory mechanism for RBC production when there’s something wrong with the bone marrow?
Liver and spleen can start to make RBCs when the BM is destroyed or in myeloproliferative diseases
In adulthood, where specifically does hematopoiesis occur?
Medullary cavity of bones in the axial skeleton = vertebrae, ribs, pelvis, femur
What’s the maturation sequence of RBCs?
Blast, basophilic erythroblast, polychromatophilic erythroblast, orthochromic erythroblast, polychromatophilic RBC (reticulocyte), mature RBC
What’s the maturation of WBCs?
Myeloid: blast, progranulocyte, myelocyte, metamyelocyte, band, neutrophil (or eo or baso)
What causes pluripotent stem cells to differentiate into specific things?
Under the influence of specific cytokines, pluripotent stem cells will turn into either common myeloid stem cells or common lymphoid stem cells
Lymphoid stem cells will then turn into plasma cells, NK cells and T cells
Myeloid cells will then turn into eosinophils, basophils, RBCs, monocytes/macrophages, leukocytes, platelets
What are the most important growth factors for stem cells?
SCF (c-KIT ligand)
Flt3-ligand
What are the most important growth factors for granulocytes?
GM-CSF
What are the most important growth factors for eosinophils?
IL-5
What are the most important growth factors for monocytes?
M-CSF
What are the most important growth factors for RBC?
Erythropoietin
What are the most important growth factors for megakaryocytes/platelets?
Thrombopoietin
What are the most important growth factors for B cells?
Flt3L
What are the most important growth factors for T cells?
IL-7
What are the most important growth factors for NK cells?
IL-15
What’s the diameter of a RBC?
6-9 microns
What’s the average concentration of Hb in men and women?
13.-17 g/dl in men
12-15 g/dl in women
What’s the normal RBC count in men and women?
- 3-6 million/mm^3 in men
3. 5-5 million/mm^3 in women
What does RBC carbonic anhydrase do?
Rapidly inter-converts CO2 and water into carbonic acid acid, protons and bicarbonate ions
Important in buffering H+ ions to maintain pH
This can effect serum K+: in metabolic acidosis, patients can become hyperkalemic
Congenital loss of an RBC’s biconcave shape may lead to which of the following diseases?
- hemophilia
- Hereditary spherocytosis
- Pernicious anemia
- Thrombocytosis
- Von willebrand disease
Hereditary spherocytosis
What is herediary spherocytosis?
Congenital disorder of RBCs resulting from mutations in RBC cytoskeleton proteins and proteins that attach the cytoskeleton to the cell membrane
Mutations in proteins like spectrin and ankyrin make the membrane cytoskeleton unstable and the RBCs are more likely to lyse
Why is an RBC’s lactic-like structure advantageous?
Enhanced ability to maneuver through small blood vessels
What are the components of HbA and % of Hb?
96%
2 alpha chains, 2 beta chains, 4 Fe-containing hemes
What replaces oxygen when it’s released from Hb?
When oxygen is released 2,3-disphosphoglycerate replaces it to make deoxyHb
What color is oxygenated vs. deoxygenated blood?
Oxygenated, arterial = red
Deoxygenated, venous = blood
What’s the structure of HbA2 and % of Hb?
2%
2 alpha chains, 2 delta chains
What’s the structure of HbF and % of Hb?
1%
2 alpha and 2 gamma
What transmembrane proteins are in the RBC membrane?
- glycophorins A, B,C,D
- ion channels for Na+, K+, Ca+2
- band 3 transports Cl- and HCO3-
What makes up the RBC membrane?
- transmembrane proteins
- cytoskeleton proteins
- surface carbohydrates
What cytoskeleton proteins are in the RBC membrane?
Ankyrin, spectrin, band 4.1
Membrane defects cause hereditary spherocytosis
What do surface carbohydrates on RBC do?
Determine blood group and Rh type!
O,A,B,AB
Important for transfusion
How do WBC exit the vascular space?
Diapedesis
How they make it through basement membrane to get into tissue spaces
What are the two groups of WBCs?
Granulocytes: neutrophils, eosinophils, basophils
- segmented nucleus, cytoplasmic specific granules
Mononuclear cells: lymphocytes, monocytes
- non-segmented nucleus, no specific granules
What’s the normal WBC count in adults?
4500-11,000 cells/mm^3
What type of WBC is most common?
Neutrophils
What’s the % and absolute count of neutrophils?
57-67% of WBC
2500-7400 cells/mm^3
What’s the % and absolute count of lymphocytes?
25-33%
1,125-3630 cells/mm^3
What’s the % and absolute count of monocytes?
3-7%
135-770 cells/mm^3
What’s the % and absolute count of eosinophils?
1-3%
45-330 cells/mm^3
What’s the % and absolute count of basophils?
<1%
<110 cells/mm^3
What are the characteristics of neutrophils?
Multi-lobed nucleus
Motile
Phagocytic (due to lysosomes and granules)
Condense chromatin in nucleus = no protein synthesis
Few organelles in cytoplasm
What help with neutrophil diapedesis?
Selections and ICAM-1 adherence
What helps neutrophils with chemotaxis?
Chemotaxis = traveling from one place to another
IL-1 and TNF
How do neutrophils phagocytize and destroy bacteria in connective tissue spaces?
Via reactive oxygen compounds = free radicals
What enzyme helps neutrophils phagocytize bacteria? What test can be done to check if a neutrophil has this enzyme? What disease do you get if you don’t have this enzyme?
NADPH oxidase
Chronic granulomatous disease results from NADPH oxidase deficiency
PMNs are unable to kill bacteria and these giant inflammatory granules build up
Nitro blue tetrazolium test tells you if a PMN has NADPH oxidase
What do the primary granules of neutrophils contain?
Azurophilic granules = primary granules
Peroxidase & lysozyme
What do the secondary granules of neutrophils contain?
Specific granules = secondary granules
Collagenase, phospholipase, lactoferrin, lysozyme, alkaline phosphatase, vitamin B12-binding protein, phagocytin
What do the tertiary granules of neutrophils contain?
Gelatinase & cathepsin
What does an elevated neutrophil count indicate?
Bacterial infection
Are neutrophils smaller or larger than RBC?
Larger
Why are neutrophils one of the quickest responders to an inflammation?
Half of all neutrophils in the blood are marginated to the blood vessel wall
If a woman has large RBCs and hypersegmented neutrophils in her blood smear and she is a vegan and says she’s fatigued. What vitamin deficiency does she probably have?
Vitamin B12
Deficiency can cause megaloblastic anemia and hypersegmented neutrophils
B12 is in animal products like fish, meat, poultry, eggs
What does the nucleus of an eosinophil look like?
Bi-lobed
What do eosinophils do?
Important for moderating allergic reactions and killing parasitic words
What do specific granules of eosinophils contain?
Crystalline core (internum) and a less dense matrix (externum)
Internum: major basic protein, eocationic protein, eo-derived neurotoxin
Externum: aryl sulfatase, histaminase
Which compounds in the specific granules of eosinophils help fight parasitic infections?
major basic protein and eocationic protein
Are eosinophils bigger or smaller than neutrophils?
Bigger!
Eosinophil > neutrophil > RBC
12-17 micrometers
What color do eosinophils stain? Why?
They have large acidophilic specific granules so they stain bright red!
Eosin is acidic and stains stuff pink so if the granules are acidophilic then they’ll turn pink
What cytokine is important for eosinophil production and release from bone marrow?
IL-5
What chemical influencers allow for eosinophil chemotaxis?
Histamine, leukotrienes, eosinophil chemotactic factor
What’s the pneumonic for eosinophil function?
NAACP
Neoplasia, allergy, asthma, collagen vascular diseases, parasites
Eosinophils function in allergic reactions, inflammatory reactions and parasitic worm invasion - they inactivate some inflammatory substances like histamine
Neoplasia = uncontrolled growth of cells in the body (cancer)
What substance will help the eosinophil find its way to the right place in the body?
Eosinophil chemotactic factor
ECF is released by other WBCs to attract eosinophils to the site of action in the body
What substances kill parasites and degrade antigen-antibody complexes?
Peroxidases and hydrolases
What does the basophil nucleus look like?
S shaped nucleus
2-3 irregularly shaped lobes
What is the function of basophils?
Act as an initiator in the inflammatory process and allergic reactions
They are involved in production of mediators of inflammation like:
- platelet-activating factor
- leukotrienes
- prostaglandins: SRS-A slow reacting substance of anaphylaxis, bradykinins, TNF, interleukins
What do the specific granules of basophils have?
- Histamine
- heparin
- eosinophil chemotactic factor
- peroxidase
- condroitin sulfate
What color do the granules of basophils stain?
Deep blue stained granules (basic)
Usually the granules cover up the nucleus and you can’t see it
What do basophils do in tissues?
They bind IgE when antigen contact occurs and then the basophils release granules
What does histamine do?
Causes vasodilation, smooth muscle contraction, leaky blood vessels
These reactions all mediate allergic and anaphylactic reactions in tissues
What medical condition do you suspect if there’s ever basophilia?
It’s rarely seen since basophils make up such a small portion of the blood
But when it does happen you usually suspect leukemia = blood cancer
What’s the main component of basophil specific granules?
Histamine and heparin
Other: lysosomal enzymes, peroxidase, eosinophil and neutrophil chemotactic factors
What do monocytes do?
In the blood they’re monocytes but then they enter the connective tissue space and become macrophage
- They produce cytokines
- Can present antigens to T-cells
What is the largest type of WBC?
Monocytes
20 micrometer
What does the monocytes nucleus look like?
Kidney bean shape/u-shape but one lobe!
Lots of cytoplasm
“Raked” chromatin
When a monocytes encounters a microbe what does it do to get rid of it?
Ingests/phagocytose the microbe
Completely engulfs substance and removes it from circulation
What types of things to monocytes phagocytose?
Old RBC, antigens, foreign particulate material including bacteria
What is a granuloma?
A collection of macrophages that are fused together into one giant macrophage
Usually happens in tuberculosis and fungal infections
How big are lymphocytes?
Usually small, just a little bigger than RBCs
About 10% are bigger and have more cytoplasm, more free ribosomes and more mitochondria = usually activated lymphocytes
What does the nucleus of a lymphocyte look like?
Spherical nucleus
Abundant dark staining condensed chromatin
Not a lot of cytoplasm can be seen
Basophilic = stains blue/purple
Nucleus takes up most of the cell!!
What are the types of lymphocytes?
- B-lymphocytes (15%)
- T-lymphocytes (80%)
- NK cells (5%)
What do B-lymphocytes do?
- humoral immunity: antibody mediated immunity
- activated B-cells produce plasma cells which then produce antibodies
- antibodies circulated throughout body by blood and lymph
What do T-lymphocytes do?
- cell immunity
- helper T cells and T-regulatory cells are required to activate B-cells
- cytotoxic T cells directly kill foreign/virus infected cells
What do NK cells do?
Attack virus infected cells, cancer cells or transplanted cells without need for stimulation
Aka they’re innate
Where are lymphocytes produced?
All produced in the bone marrow but T-cells go to the thymus to mature
What part of the immune system are the different types of lymphocytes?
B and T cells = adaptive immune system
NK cells = innate immune system
What cell marker identifies a helper T cell?
CD4
What cell marker do all T cells have?
CD3
What cell marker do cytotoxic T cells have?
CD8
What cell marker do regulatory T cells have?
CD25
What cell marker to NK cells have?
CD56
Do platelets have a nucleus?
No but they do have organelles!
Where do platelets come from?
They fragment off of megakaryocytes in the bone marrow! That’s why they don’t have nucleus
What’s the function of platelets?
Primary hemostatic plug in damaged blood vessels
Secondary hemostasis is the coagulation cascade
What disease is characterized by abnormal platelet adhesion?
Bernard-Soulier syndrome
Platelet receptor GpIb is congenitally lost
GpIb allows platelets to adhere themselves tot he injured blood vessel in an attempt to achieve hemostasis
What is Glanzmann thrombasthenia?
Platelet aggregation or clumpin is abnormal due to lack of GpIIb/IIIa receptors
A patient has a rash all over her lower extremeties. She has thrombocytopenia. What can be found in the alpha granules of the platelets?
Growth factors, adhesion molecules, von Willebrand factor, fibrinogen
Dense granules have ADP, ATP, serotonin and Ca+2
