Module 2 - Structure and Function of the hematological systm Flashcards
Blood volumes amounts to how many L in adults?
5.5 L
What is the composition of blood?
- It is made up of various cells - suspended in a solution of protein and inorganic materials (plasma).
- Solution is approximately 92% water and 8% solutes
List the functions of blood
- delivery of substances needed for cellular metabolism in the tissues
- removal of wastes
- defence against invading organisms or injury
- maintenance of acid-base balance
Plasma protein accounts for how much percentage in blood for adults?
50-55%
Describe Plasma
- complex liquid - has organic and inorganic parts
- concentration depends on diet, metabolic demand, hormones, and vitamins
How does plasma differ from serum?
Serum is plasma that has been allowed to clot in the lab to remove fibrinogen and other clotting factors that may interfere with diagnostic tests.
What is the function of water in the plasma?
medium for carrying all constituents
What is the function of electrolytes in the plasma?
Maintenance of H2O in extracellular compartment. Acts as buffers and function in membrane excitability
What is the function of protein in the plasma?
Provision of colloid osmotic pressure of plasma, act as buffers
What is the function of CO2 in plasma?
By product of oxygenation; most co2 content is from HCO3- and acts as a buffer
What are the 2 major groups of protein in the plasma?
albumin and globulins
Which organ produces most of plasma proteins?
liver
What do plasma cells in the lymph nodes produce?
antibodies
This protein composes 60% of plasma protein?
Albumin
This protein acts as a carrier molecule for components of blood and medications.
Albumin
What is the key role of albumin?
regulation of the passage of water and solutes through capillaries.
What does the albumin help maintain?
It helps maintain the critical colloidal osmotic pressure (oncotic pressure) that regulates the passage of fluids and electrolytes into the surrounding tissues.
How are globulins classified?
By their movement compared.
What are the different types of globulin?
-alpha globulins (those moving most closely to albumin),
-beta globulins, and gamma globulins (those with the least movement).
This is a major plasma protein that is about 4% of total plasma. It would move between the beta and gamma regions but is removed during the formation of serum.
Fibrinogen
What does the gamma-globulin region mostly consist of?
antibodies
What are the functions of plasma proteins?
- clotting
- defence
- transport
- regulation
What does clotting factors do?
Promote coagulation and stop bleeding from damaged blood vessels.
What is fibrinogen?
Most plentiful of the clotting factors and precursor to fibrin clot.
Most plentiful of the clotting factors and precursor to fibrin clot.
Fibrinogen
What are the proteins that are involved in defence or protection against infection?
antibodies and complement proteins
What does transport proteins do?
Bind an carry a variety of inorganic and organic molecules. These include iron, copper, lipids, and steroid hormones, and vitamins.
What do regulatory proteins do?
Regulatory proteins include a variety of enzymatic inhibitors (e.g., α1-antitrypsin) that protect the tissues from damage, precursor molecules (e.g., kininogen) that are converted into active biological molecules when needed, and protein hormones (e.g., cytokines) that communicate between cells.
What are the inorganic ions in plasma that regulate cell function, osmotic pressure and blood PH.
Electrolytes, Na, K, Calcium, chloride and phosphate.
What are the cellular components of blood?
- Erythrocytes
- Leukocytes
- Platelets.
What is the most abundant cells of the blood.
Erythrocytes.
How much percentage of the blood volume does RBC occupy?
48% in men and 42% in women
What is the main role of RBC?
Tissue oxygenation
What component carries the gases
Hemoglobin
What does the mature erythrocyte lack?
nucleus and cytoplasmic organelle
What are some the things the mature erythrocyte is unable to do?
- It cannot create protein or carry out oxidative reactions
- Does not go mitotic division
What is the lifespan of the erythrocyte?
80-120 days
what is the size and shape of RBC
Its a small disc with a biconcave shape and has the capacity to reversibly deformed.
What are the functions of leukocytes?
- defence
- remove debris
How are leukocytes classified?
Through their structure and function
Name the different types of leukocytes according to their structures
granulocytes and agranulocytes
What are the different types of granulocytes?
- Neutrophils
- Basophils
- Eosinophils
These are all phagocytes
List the different types of Leukocytes according to their function?
Phagocytes and immunocytes.
List agranulocytes that are phagocytes?
monocytes and macrophages
List agranulocytes that are immunocytes?
lymphocytes
What does granulocytes have in their cytoplasm?
they have membrane-bound granules
What do the granules in the granulocytes contain?
- enzymes capable of killing microorganism and catabolizing debris ingested during phagocytosis.
- also holds powerful biochemical mediators with inflammatory and immune functions.
What are the granulocytes capable of in order to get to sites where their action is needed?
Movement through vessel walls (diapedisis)
What is the most numerous granulocyte
Neutrophil
What percentage does neutrophil make up of the total leukocyte count in adults?
60-70%
What are the chief phagocytes of early inflammation?
Neutrophils
What does neutrophils do soon after bacterial invasion or tissue injury?
- Neutrophils migrate out of the capillaries and into the damaged tissue
- At the site of injury, they ingest and destroy contaminating microorganism and debris.
What is the lifecycle of neutrophil?
1-2 days - they are sensitive to the environment in the damaged tissue.
Describe eosinophils?
- They have large coarse granules
- They make up 2-4% of the normal leukocyte count in adults
Using pattern-recognition receptors, what are the eosinophils capable of?
They are capable of amoeboid movement and phagocytosis
What does eosinophil secondary granules contain?
toxic chemicals that are highly destructive to parasites and viruses
During type I hypersensitivity, allergic reactions and asthma are characterized by?
high eosinophil counts
The high eosinophil counts during type I hypersensitivity, allergic reactions and asthma are involved in?
regulation of inflammation and contribute to the destructive inflammatory processes seen in the lungs of persons who have asthma.
How much percentage does basophils make up the leukocytes?
1%
These are immature macrophages
Monocytes
Where are monocytes formed and release?
Bone marrow into the bloodstream.
Where do monocytes move as they mature and change into tissue macrophages?
liver, spleen, lymph nodes, peritoneum, gastro-intestinal tract
These make up 20 - 25% of the total leukocyte count and are primary cells of the immune system?
Lymphocytes
These resemble lymphocytes. They kill some types of tumour cells in vitro and some virus infected cells without prior exposure.
NK cells.
Where do NK cells develop and circulate?
Develop in bone marrow and circulate in the blood
Describe platelet
are not true cells but plate-like or disc-shaped anuclear cytoplasmic fragments
What are platelets essential for
are not true cells but plate-like or disc-shaped anuclear cytoplasmic fragments
How are platelets formed?
They are formed by the breaking up of large (40 to 100µm in diameter) cells known as megakaryocytes
What do platelets hold?
Platelets hold cytoplasmic granules capable of releasing strong mediators when stimulated by injury to a blood vessel
1/3 of the body’s available platelets are found where?
spleen
How long does platelet circulate for?
8-11 days and ages.
What removes platelets?
macrophages, mostly in the spleen
What joins with circulatory system?
Lymphoid system
What are the classification of lymphoid organs?
Primary and secondary
What are the primary lymphoid organs?
Thymus and bone marrow
What are the secondary lymphoid organs?
spleen, lymph nodes, tonsils, peyer patches of the small intestines.
This is the largest lymphoid organ
spleen
What are the functions of spleen?
- It serves as a site of fetal hematopoiesis,
-filters and cleanses the blood by mononuclear phagocytes,
-and starts an immune response to bloodborne microorganisms.
-It is also a reservoir for blood.
What can happen after splenectomy?
-Leukocytosis - This finding suggests that the spleen has some control over the rate of proliferation of leukocyte stem cells in the bone marrow or their release into the bloodstream.
- iron level decreases - reflecting the spleen’s role in the iron cycle.
- The immune response to encapsulated bacteria, which is primarily an immunoglobulin M (IgM) response, may be severely decreased. This decrease results in increased susceptibility to disseminated infections.
- Loss of the spleen results in an increase in morphologically defective blood cells in the circulation. This finding confirms the spleen’s role in removing old or damaged cells.
Lymph nodes are part of which systems?
hematological and immune system
They are the primary sites for the first encounters between these 2 things.
Antigen and lymphocytes
How does lymphocytes enter the lymph node from the blood?
through the postcapillary venules by diapedesis across the endothelial lining
Where does B cell and T Cell migrate to?
B cells tend to migrate to the cortex and medulla of the nodes, while T cells migrate to the paracortex.
These leukocytes live in the lymph nodes.
Macrophages
What are the function of the macrophages in the lymph nodes?
They help filter the lymph of debris, foreign substances, and microorganisms; and supply antigen-processing functions.
What can cause lymph node enlargement?
The B-cell proliferation in response to a great deal of antigen (e.g., during infection) may result in lymph node enlargement and tenderness (reactive lymph node).
What is mononuclear phagocyte system (MPS)?
is made up of monocytes that differentiate without dividing and live in the tissues for months or perhaps years.3
Macrophages for bonemarrow
Monocytes/macrophages
Macrophages for liver
Kupffer cells (inflammatory macrophages)
Macrophages for lung
alveolar macrophages
Macrophages for connective tissue
histiocytes
Macrophages for bone marrow
macrophages
Macrophages for spleen and lymph nodes
fixed and free macrophages
Macrophages for serous and lymph nodes
fixed and free macrophages
Macrophages for nervous system
Microglial cells
Macrophages for kidney
Mesangial cells
Macrophages for bone
Osteoclasts
Macrophages for skin
Langerhans
Macrophages for lymphoid tissue
dendritic cells
What are the functions of the MPS cells that make them play an important fold in defence?
- These cells ingest and destroy (by phagocytosis) unwanted materials.
These materials include foreign protein particles, circulating immune complexes, microorganisms, debris from dead or injured cells, defective or injured erythrocytes, and dead neutrophils.
This MPS cell are specialized for the function of bone resorption; however, they are also known to have phagocytic abilities.
Osteoclast
How much new blood cells do humans require per day?
100 billion new blood cells per day
blood cell production
Hematopoiesis
Where does Hematopoiesis occur?
It occurs in the liver and spleen of the fetus and only in bone marrow (medullary hematopoiesis) after birth.
What is the process involved in hematopoeisis
This process involves the biochemical stimulation of populations of relatively undifferentiated cells to undergo mitotic division (i.e., proliferation) and maturation (i.e., differentiation) into mature hematological cells.
Which cells differentiate fully before entering the blood?
Erythrocytes and neutrophils
Which cells continue to mature in the blood and in secondary lymphatic organs?
Monocytes and lymphocytes
Where is the bone marrow found?
cavities of the bone
What is the primary residence of hematopoietic stem cells.
Bone marrow
What does the bone marrow consist of?
It consists of blood vessels, nerves, mononuclear phagocytes, stromal cells, and blood cells in various stages of differentiation.
What are the 2 kinds of bone marrow?
red, or active (hematopoietic) marrow (also called myeloid tissue); and yellow, or inactive marrow.
What makes inactive marrow appear yellow:
The large quantities of fat in inactive marrow make it yellow.
Where is active marrow found?
In adults, active marrow is found in the flat bones of the pelvis (36%), vertebrae (29%), cranium and mandible (13%), sternum and ribs (10%), upper limb girdle (8%), and in the extreme proximal portions of the femur (4%).
Where is inactive marrow found?
in the cavities of other bones.
How is hematopoietic marrow vascularized?
by the primary arteries of the bones, which end in a capillary network forming large venous sinuses.
The hematological compartment of the bone marrow is made of what?
cellular microenvironments or niches
What does niches control?
differentiation of hematopoietic progenitor cells.
What is the cellular make up of niches?
The cellular make-up of niches includes osteoblasts, osteoclasts, sinusoidal endothelial cells, fibroblasts, megakaryocytes, macrophages, and nerve cells.
This come from fibroblasts and handle construction of bone.
Osteoblasts
These are multinucleate cells of monocytic origin that remodel bone by resorption.
Osteoclasts
These cells produce cytokines that affect proliferation of hematopoietic cells.
Osteoblasts and osteoclasts
What are the 2 populations of stem cells found in the bone marrow niches?
Mesenchymal stem cells (MSCs)
Hematopoietic stem cells (HSCs)
These are stromal cells that can differentiate into a variety of cells. These cells include osteoblasts, adipocytes, and chondrocytes (produce cartilage).
Mesenchymal stem cells (MSCs)
MSC cells include what type of cells.
osteoblasts, adipocytes, and chondrocytes (produce cartilage).
These are originators of all hematological cells.
Hematopoietic stem cells (HSCs)
Where do population of stem cell under go renewal?
Bone marrow
What are the 2 types in niche?
the osteoblastic (also called endosteal) niche and the vascular niche
This niche is centralized around osteoblasts, which line the surface of bone.
osteoblastic niche
This niche is organized around sinusoidal endothelial cells.
vascular niche
What are the 2 specialized niche of osteoblastic and vascular niche?
Each niche also has two specialized cells derived from MSCs: CXCL12-abundant reticular (CAR) cells and nestin-expressing cells.5
Pluripotent
Cells have the ability to have unlimited differentiation potential.
These cells keep proliferative ability but are committed to possible further differentiation into particular types of hematological cells.
Progenitor
What cells do progenitor cells differentiate into?
These cells include lymphoid (lymphocytes, NK cells), granulocyte/monocyte (granulocytes, monocytes, macrophages), and megakaryocyte/erythroid (platelets, erythrocytes) progenitor cells.
Which cytokines particularly take part in hematopoiesis?
colony-stimulating factors (CSFs or hematopoietic growth factors).
What does CSF do?
CSFs stimulate the proliferation of progenitor cells and their progeny and start the maturation events necessary to produce fully mature cells.
What produces CSF?
Multiple cell types in hematopoietic organs, including endothelial cells, fibroblasts, and lymphocytes, produce the necessary CSFs.
Hematopoiesis in the bone marrow occurs in these 2 separate pools.
This includes the stem cell pool and the bone marrow pool.
What does stem cell pool hold?
The stem cell pool holds pluripotent stem cells and partially committed progenitor cells
What does bone marrow pool hold?
The bone marrow pool holds cells that are proliferating and maturing in preparation for release into the circulation and mature cells that are stored for later release into the peripheral blood.
What pool of cells does peripheral blood hold?
These pools include those circulating and those stored around the walls of the blood vessels (often called the marginating storage pool).
What does the marginating storage pool consists of?
neutrophils that adhere to the endothelium in vessels where the blood flow is relatively slow. These cells can quickly move into tissues and mucous membranes when needed.
What mechanisms can increase Medullary hematopoiesis?
(1) conversion of yellow bone marrow, which does not produce blood cells, to red marrow, which does, by the actions of erythropoietin (a hormone that stimulates erythrocyte production); (2) faster differentiation of daughter cells; and, presumably, (3) faster proliferation of stem cells.
This hormone stimulates erythrocyte production and help in converting yellow bone marrow to red marrow.
erythropoietin
What is the site of erythropoiesis
erythropoiesis,
What is the last immature form of erythrocyte?
reticulocyte.
This form has a meshlike (reticular) network of ribosomal RNA that is visible microscopically after staining with certain dyes.
reticulocyte
How long does reticulocytes stay in the marrow and where are they released after?
1 day, venous sinuses
Of the total red blood cell count, what percentage is the normal reticulocyte count
1%
The reticulocyte count is a useful clinical index of this activity.
of erythropoietic activity.
Why is the reticulocyte count is a useful clinical index of erythropoietic activity.
It shows whether new red blood cells are being produced. This is because about 1% of the body’s circulating erythrocyte mass normally is made every 24hours.
In conditions of tissue hypoxia, erythropoietin is secreted primarily by this area.
primarily by the peritubular cells of the kidney
Most steps of erythropoiesis are primarily under the control of this.
a feedback loop involving the glycoprotein erythropoietin.
Rising levels of erythropoietin cause a compensatory increase in this.
erythrocyte production if the oxygen content of blood decreases.
What are some of the conditions that can cause the following: Rising levels of erythropoietin cause a compensatory increase in erythrocyte production if the oxygen content of blood decreases.
This occurs because of anemia, high altitude, or pulmonary disease.
How does the body responds to reduced oxygenation of blood
(1) by increasing the intake of oxygen through increased respiration and (2) by increasing the oxygen-carrying capacity of the blood through increased erythropoiesis.
This is used in
ndividuals with anemia secondary to decreased erythropoietin from chronic renal failure.
What is the immediate effect of erythropoietin administration
an increase in the blood reticulocyte count, followed by increasing levels of erythrocytes.
What is the most most significant side effect of erythropoietin administration
High BP
Each Hb molecule is composed of the following:
two pairs of polypeptide chains (the globins) and four colourful complexes of iron plus protoporphyrin (the hemes).
The ______are responsible for the blood’s ruby-red colour
hemes
How to the several variants of Hb differ?
they differ only slightly in primary structure based on the use of different polypeptide chains: alpha, beta, gamma, delta, epsilon, or zeta (α, β, γ, δ, ε, or ζ).2
Which is the most common Hb variant in adults?
Hemoglobin A (Hb A)
What is Hb A composed of?
is composed of two α- and two β-polypeptide chains (α2β2).
This normal variant binds oxygen with a much greater affinity than adult Hb.
fetal hemoglobin (Hb F), is a complex of two α- and two γ-polypeptide chains
Heme is a large, flat, iron-protoporphyrin disc.
Heme
Where is heme synthesized
synthesized in the mitochondria and can carry one molecule of oxygen
How many oxygen molecules does 1 indivudiual hb carry?
Thus, an individual Hb molecule with its four hemes can carry four oxygen molecules.
What directly competes with oxygen for binding to ferrous ion with an affinity that is about 200-fold greater than that of oxygen.
CO2
This may play a role in the maintenance of vascular relaxation.
Erythrocytes
This produced by blood vessels is a major mediator of relaxation and dilation of the vessel walls.
Nitric Oxide
What is the role of protein in Erythropoiesis?
Structural part of plasma membrane
What is the role of synthesis of Hb n Erythropoiesis?
Decreased erythropoiesis and lifespan of erythrocytes
What is consequence of deficiency of protein?
Decreased strength, elasticity, and flexibility of membrane; hemolytic anemia
What is the role of IF Erythropoiesis?
Gastro-intestinal absorption of vitamin B12
What is consequence of deficiency of IF?
Pernicious anemia
What is the role of Cobalamin Erythropoiesis?
Synthesis of DNA, maturation of erythrocytes, facilitator of folate metabolism
What is consequence of deficiency of Cobalamin?
Macrocytic (megaloblastic) anemia
What is consequence of deficiency of Folate (folic acid)?
Macrocytic (megaloblastic) anemia
What is the role of folate (folic acid) in Erythropoiesis?
Synthesis of DNA and RNA, maturation of erythrocytes
What is the role of Vit B6 pyroxidine in Erythropoiesis?
Heme synthesis, possibly increases folate metabolism
What is consequence of deficiency of Vitamin B6 Pyrixodine?
Hypochromic-microcytic anemia
What is the role of Vit B2 riboflavin in Erythropoiesis?
Oxidative reactions
What is consequence of deficiency of Vitamin B2 riboflavin?
Normochromic-normocytic anemia
What is the role of Vit C (ascorbic acid) in Erythropoiesis?
Iron metabolism, acts as reducing agent to support iron in its ferrous (Fe++) form
What is consequence of deficiency of Vitamin C (ascorbic acid)?
Normochromic-normocytic anemia
What is the role of Pantothenic acid in Erythropoiesis?
Heme synthesis
What is the role of Niacin in Erythropoiesis?
None, but needed for respiration in mature erythrocytes
What is the role of Vit E in Erythropoiesis?
Synthesis of heme; possible protection against oxidative damage in mature erythrocytes
What is the role of Iron in Erythropoiesis?
Hemoglobin synthesis
What is the consequence of deficiency iron?
Iron deficiency anemia
What is the role of copper in Erythropoiesis?
Structural part of plasma membrane
What is the consequence of deficiency copper?
Hypochromic-microcytic anemia
Erythropoiesis cannot proceed in the absence of the following vitamins.
vitamin B12, folate (folic acid), vitamin B6, riboflavin, pantothenic acid, niacin, ascorbic acid, and vitamin E.
This vitamin is a large molecule that requires a protein secreted by parietal cells into the stomach (intrinsic factor) for transport across the ileum.
Vitamin B12
Where is Vit B12 Stored.
Liver
Where does folate absorption happen and where is it stored. ?
mainly in the upper small intestine and is stored in the liver
About what percentage of total body iron is bound to heme in erythrocytes (Hb) and muscle cells
67%
About what percentage of iron is stored in mononuclear phagocytes (i.e., macrophages) and hepatic parenchymal cells as either ferritin or hemosiderin.2
30%
What percentage of iron is lost daily in urine, sweat, bile, sloughing of epithelial cells from the skin and intestinal mucosa, and minor bleeding.
3%
how much mg of iron is needed daily for erythropoiesis.
25 mg
How much mg of iron is dietary?
Only 1 to 2mg of iron is dietary
The protein is the major intracellular iron storage protein.
ferritin
This is ferritin without attached iron, can store thousands of atoms of iron.
Apoferritin
micelle ferritin
Several apoferritin complexes combined
hemosiderin.
large iron storage complexes made by large groups of micelles
What is common cause of hemosiderin deposition
simple bruising
When does iron become transferrin?
When Iron from any dietary source, release of iron stores, or erythrocyte catabolism is transported in the blood bound to apotransferrin,
This glycoprotein synthesized primarily by hepatocytes in the liver. It is also produced in small amounts by tissue macrophages, submaxillary and mammary glands, and ovaries or testes
Apotransferrin
Iron not used in erythropoiesis is stored temporarily as _______and _______
ferritin or hemosiderin and later excreted.
The body’s iron homeostasis is mainly controlled by the hormone _________.
Hepcidin
This is a 25–amino acid peptide made in the liver and released into the plasma.
Hepcidin
what regulates hepatocellular hepcidin production ?
levels of iron in the body, rate of erythropoiesis, and percentage of oxygen saturation.
How does Hepatocytes (liver cells) sense levels of circulating iron
receptors for transferrin
How is hepcidin production induced?
by inflammation via IL-6.
How does Hepcidin regulate iron levels?
through its binding capacity to ferroportin.
This is a transmembrane iron exporter found in the plasma membrane of cells that transport or store iron.
Ferroportin
Where is ferroportin found?
It is found in macrophages, hepatocytes, and enterocytes (intestinal cells).
Leukocytes consist of the following?
Leukocytes consist of lymphocytes, granulocytes, and monocytes.
Most leukocytes come from ________________that differentiate into common lymphoid progenitors and common myeloid progenitors
HSCs in the bone marrow
What develops into lymphocytes?
Lymphoid progenitor cells
What happens when lymphocytes enter the bloodstream?
The lymphocytes enter the bloodstream to undergo further maturation in the primary and secondary lymphoid organs
Common myeloid progenitors further differentiate into what?
progenitors for erythrocytes, megakaryocytes, and mast cells, and into granulocyte/monocyte progenitors.
Granulocytes are released into the blood within ______development.
14 days
Monocytic progenitors differentiate into monocytes _________ and are released into the circulation.
within 24hours
How long does int take for monocytes to mature into various forms of macrophages?
This process is usually complete within 1 or 2 days after release.
What factors can increase leukocyte production?
to infection, to the presence of steroids, and to reduction or depletion of reserves in the marrow. It also is associated with strenuous exercise, convulsive seizures, heat, intense radiation, paroxysmal tachycardias (outbursts of rapid heart rate), pain, nausea and vomiting, and anxiety.
Where are platelets derived from ?
Platelets (thrombocytes) are derived from stem cells and progenitor cells that differentiate into megakaryocytes.
Like erythrocytes, platelets released from the bone marrow lack ______________
nuclei.
About ____ of platelets enter the circulation and rest exist in the _______.
2/3, splenic pool.
Platelets circulate in the bloodstream for about________before beginning to lose their ability to carry out biochemical reactions.
10 days
What sequesters and destroys aging platelets by mononuclear cell phagocytosis.
Spleen
What is Thrombopoietin (TPO),
a hormone growth factor, is the main regulator of the circulating platelet numbers.
Where is TPO produced?
Liver
What happens when platelet levels are normal?
TPO is adsorbed onto the platelet surface and prevented from accessing the bone marrow and initiating further platelet production.7
What happens when platelet numbers are low?
the amount of TPO exceeds the number of available platelet TPO receptors, and free TPO can enter the bone marrow.
During inflammation,what induces increased production of TPO.
IL-6
what are Three equally important components of hemostasis
platelets, clotting factors, and the vasculature (endothelial cells and subendothelial matrix).
Arrest of bleeding
Hemostatis
general sequence of events in hemostasis:
1.Vascular injury leads to a transient arteriolar vasoconstriction to limit blood flow to the affected site;
2.Damage to the endothelial cell lining of the vessel exposes the prothrombogenic subendothelial connective tissue matrix, leading to platelet adherence and activation and formation of a hemostatic plug, also referred to as a platelet plug, to prevent further bleeding (primary hemostasis);
3.Tissue factor, produced by the endothelium, collaborates with secreted platelet factors and activated platelets to activate the clotting (coagulation) system to form fibrin clots and further prevent bleeding (secondary hemostasis);
4.The fibrin/platelet clot contracts to form a more permanent plug; and
5.Regulatory pathways are activated (fibrinolysis) to limit the size of the plug and begin the healing process.
These two substances help support blood flow, blood pressure, and inhibit platelet adhesion and aggregation.
NO and the prostaglandin derivative prostacyclin (PGI2).
The endothelial cell surface has antithrombotic molecules, such as glycosaminoglycans (e.g., heparan sulphate), thrombomodulin, and plasminogen activators. What are their functions?
These limit platelet activation and fibrin deposition.
What is the role of platelet activation?
1) contribute to regulation of blood flow into a damaged site through induction of vasoconstriction (vasospasm); (2) initiate platelet-to-platelet interactions resulting in formation of a platelet plug to stop further bleeding;
(3) activate the coagulation (or clotting) cascade to stabilize the platelet plug; and
(4) initiate repair processes, including clot retraction and clot dissolution.
A platelet count below 150000/mm3 is defined as _________.
thrombocytopenia
When does thrombocytopenia become symptomatic?
thrombocytopenia is usually asymptomatic unless the count drops below 100×109/L.
What happens When the number of platelets is inadequate,
abnormal bleeding may occur in response to trauma.
Spontaneous major bleeding episodes do not generally occur unless the platelet count falls below _______-
20×109/L.
Describe platelet activation process.
(1) increased adhesion to the damaged vascular wall; (2) platelet degranulation, which stimulates changes in platelet shape; (3) aggregation as platelet–vascular wall and platelet-platelet adherence increases; and (4) activation of the clotting system and development of an immobilizing meshwork of platelets and fibrin
What are the 3 types of granules that platelets have ?
Platelets have three types of granules—lysosomes, dense bodies, and alpha granules.
Give examples of dense bodies?
(e.g., ADP, calcium, and serotonin).
List the functions of ADP dense body
-ADP recruits and activates other platelets through specific receptors.
-ADP also induces the platelet plasma membrane to undergo three important changes. The first change includes becoming ruffled and sticky.
-They also undergo cellular spreading to make tight contacts between neighbouring platelets, causing the platelet plug to seal the injured endothelium.
- Lastly, they undergo externalization of the phospholipid phosphatidylserine, which provides a matrix for activation of clotting factors.
__________ is a vasoactive amine with histamine-like properties to increase vasodilation and vascular permeability
Serotonin
___________ is necessary for many of the intracellular signalling mechanisms that control platelet activation.
Calcium
How long does it take for the plug to usually form after injury
3-5 minutes
A _________________ is a meshwork of protein strands.
blood clot
What do the protein strands in a blood clot do
These strands stabilize the platelet plug and trap other cells, such as erythrocytes, phagocytes, and microorganisms
what makes up the protein strands in blood clot?
The strands are made of fibrin, which is produced by the clotting (coagulation) system.
What are the 2 pathways of intitiation of the clotting system?
(intrinsic and extrinsic pathways) that join in a common pathway.
How is intrinsic pathway initiated?
The intrinsic pathway is activated when Hageman factor (factor XII) in plasma contacts negatively charged subendothelial substances exposed by vascular injury.
How is extrinsic pathway initiated?
The extrinsic pathway is activated when tissue thromboplastin, a substance released by damaged endothelial cells, reacts with clotting factors, particularly factor VII.
Extrinsic and intrinsic factor leads to:
the common pathway and activation of factor X, which continues to clot formation.
Explain -there also is interaction between components of the intrinsic and extrinsic pathways.
An activated member of one pathway may activate a member of the other pathway (e.g., factor VIIa of the extrinsic pathway can directly activate factor IX of the intrinsic pathway).
What does thrombin convert?
Thrombin then converts fibrinogen into fibrin, which polymerizes into a fibrin clot.
What are the activities of thrombin in the inflammatory response?
In addition to producing fibrin, thrombin is an activator of other substances. This includes coagulation proteins (e.g., factors V, VIII, XI, XIII), platelets (e.g., aggregation, degranulation), endothelial cells (e.g., upregulation of adhesion molecules for leukocytes, increased NO, PGI2, PDGF), and monocytes (e.g., cytokine secretion, increased receptors for endothelial cells).
How is hemostatis prevented under normal conditions.
Under normal conditions, spontaneous activation of hemostasis is prevented by factors existing on the endothelial cell surface. These include thrombin inhibitors (e.g., antithrombin III), tissue factor inhibitors (e.g., tissue factor pathway inhibitor), and mechanisms for degrading activated clotting factors (e.g., protein C).
__________is a circulating inhibitor of plasma serine proteases.
Antithrombin III (AT-III)
What does AT-III do and where is it produced.
AT-III is produced by the liver and binds to heparin sulphate found naturally on the surface of endothelial cells. It is also produced with heparin administered clinically to prevent thrombosis.
What does heparin do to AT-III
Heparin induces a change in AT-III that greatly improves its ability to inhibit thrombin and other activated clotting factors.
Endothelial cells and platelets produce this.
tissue factor pathway inhibitor (TFPI).
What does TFPI do
TFPI works with and reversibly inhibits factor Xa in the prothrombinase complex. It also inhibits other activated clotting factors.
This is a thrombin-binding protein on the surface of endothelial cells.
Thrombomodulin
What binds to thrombomodulin in a thrombin-dependent manner and is converted to activated protein C.
Protein C
What does Activated protein C, in association with a cofactor
degrades factors Va and VIIIa.
What process can enhance clot formation ?
Expression of thrombomodulin and the endothelial cell protein C receptor is downregulated by cytokines and other products of inflammation (e.g., IL-1α, TNF-α, endotoxin).
What happens when a clot is formed/?
- it retracts, or “solidifies.”
- Fibrin strands shorten, becoming denser and stronger. - This process approximates the edges of the injured vessel wall and seals the site of injury.
What helps retraction ?
- Retraction is helped by the large numbers of platelets trapped within the fibrin meshwork.
- The platelets contract and “pull” the fibrin threads closer together while releasing a factor that stabilizes the fibrin.
What happens with contraction?
Contraction expels serum from the fibrin meshwork (see Figure 20.18). This process usually begins within a few minutes after a clot has formed. Expulsion of most of the serum occurs within 20 to 60minutes.
What carries out breakdown of blood clots?
Contraction expels serum from the fibrin meshwork (see Figure 20.18). This process usually begins within a few minutes after a clot has formed. Expulsion of most of the serum occurs within 20 to 60minutes.
What converts plasminogen to plasmin?
several products of coagulation and inflammation, especially by the enzymatic action of tissue plasminogen activator (t-PA).
Another activator of plasminogen
urokinaselike plasminogen activator (u-PA)
The u-PA binds to this causing activation of plasminogen.
a specific cellular urokinaselike plasminogen activator receptor (u-PAR),
This is the major activator of fibrinolysis in the extravascular or tissue compartment
urokinase
This is largely involved in intravascular fibrinolysis.
t-PA
This is an enzyme that dissolves clots (fibrinolysis).
Plasmin
How does plasmin dissolve clots.
This occurs by degrading fibrin and fibrinogen into fibrin degradation products (FDPs)
What is a major FDP
A major FDP is D-dimer.
Measurement of levels of circulating D-dimer has been used for diagnosis of what type of conditions
deep venous thrombosis or pulmonary embolism.
What are some geriatric considerations with blood ?
- Total serum iron level, total iron-binding capacity, and intestinal iron absorption are all decreased slightly in older persons.
- The erythrocyte lifespan is normal, although the erythrocytes are replenished more slowly after bleeding.
- Hemoglobin levels may be low, and the plasma membranes of erythrocytes become increasingly fragile and structurally altered.
- Lymphocyte function appears to decrease with age (see Chapters 7 and 8). This decrease causes changes in cellular immunity and some decline in T-cell function. The humoral immune system is less able to respond to antigenic challenge.
- platelet adhesiveness probably increases.
- fibrinogen levels and levels of factors V, VII, and IX tend to be increased
