Chp 28-Structure & Function of the hematologic system Flashcards
RBC does what
Provides oxygen and remove carbon dioxide
Composition of blood
92% water and 8% dissolved substances. Blood volume amounts to about 6 quarts (5.5L)
Chief functions of blood
1-deliver substances needed for cellular metabolism in tissues.
2-Removal of wastes of cellular metabolism
3-Defense against invading micro-organisms and injury
4-Maintenance of acid-base balance.
Plasma
- Aqueous liquid containing a variety of organic and inorganic elements.
- 50-55% of the blood volume
- Concentration of the materials is dependent on diet, metabolic demand, hormones and vitamins
- Plasma proteins: Albumin and globulins-which most are produced by the liver
Albumin
Carrier molecule for normal components of blood as well as drugs that have low solubility in water (e.g fatty acids, lipid-soluble hormones, thyroid hormones, bile salts).
- Most essential role is regulation or passage of water and solutes through capillaries
- Large and don’t diffuse freely-hence the colliodal osmotic pressure that regulates passage of water and solutes for surrounding tissues
- Draws fluid from intravascular to the blood vessels (useful for shock, burns, surgeries, serious injuries)
Other plasma proteins
- Globulins 38%
- Fibrinogen 4%
- Prothrombin 1%
- Plasma proteins can also be classified based on function: clotting, defense, transport, or regulation
Cellular components of blood: Erythrocytes
RBCs: most abundant cells of the blood-primarily responsible for tissue oxygenation
- Contains hemoglobin
- Limited lifespand (100-120 days)
- Removed from circulation by the spleen to be replaced by new erythrocytes
RBC shape
- Biconcave
- Reversible deformed
Leukocytes
WBCs
- Act primarily in the tissues but are transported in the circulation (5000-10,000)
- Classified by structure as either granulocytes or agranulocytes and according to function as phagocytes or immunocytes.
Granulocytes
Neutrophils, basophils and eosinophils (all are phagocytes)
- Also mast cells
- Have membrane bound granules in the cytoplasm. Contain enzymes that kill. Also contain biochemical mediators with inflammatory and immune functions
Agranulocytes
- monocytes and macrophages (phagocytes)
- whereas lymphocytes are immunocytes (cells that create immunity)
Neutrophils (PMN)
Most numerous
- Reach a fully mature state in the bone marrow.
- Normally takes 14 days to develop but accelerated according to infection and treatment w/ colony stimulating factors.
- Chief phagocyte for early inflammation
- Die within 1-2 days after use.
Eosinophils
- Ingest antigen-antibody complexes and viruses.
- Attack parasite and other pathogens
- Contain toxic chemicals
- Type 1 hypersensitivity reactions-allergic reactions (inflammatory state from lungs or people with asthma is common)
Basophils
- Abundant mixture of biochemical mediators, including histamine, chemotactic factors, proteolytic enzymes, leukotrienes and cytokines.
- Increase in numbers to allergic inflammatory reactions and parasitic infections (ticks).
- B cell differentiated driven with plasma cells that secrete IgE
- secrete heparin
Mast cells
- highly similar to basophils
- Reside in vascularized connective tissue just beneath the body epithelial surface-GI and respiratory tracts-central roles in inflammation
Macrophages
- remove old and damaged cells and large molecular substances from blood. (damaged RBCs, platelets-removed from spleen, dead neutrophils.
- Initiate wound healing
Lymphocytes
reside in secondary lymphoid tissues as mature T and B cells and plasma cells
Platelets
- Thrombocytes: Blood coagulation
- An additional 1/3 of bodies available platelets reside in the spleen (300 mL).
Lymphoid organs
- Primary: Thymus, bone marrow
- Secondary: spleen, lymph nodes, tonsils, peyer patches in the ileum of the small intestine.
Spleen
-Site for fetal hematopoiesis, filters blood-borne antigens, cleanses blood through the action of mononuclear phagocytes, initates immune responses to blood borne microorganisms, destroys ages RBCs, and reservoir for blood.
Composition of spleen
- Located on left upper abdomen and curved around the stomach
- Lymphoid follicles consist primarily of B lymphocytes-chief sites of immune function
- Venous sinuses-red pulp-storing more than 300mL of blood. (sudden drop in BP cause SNS to stimulate constriction of sinuses, resulting in expulsion of as much as 200mL in the venous circulation-increases hct by as much as 4%)
- White pulp contain the areas of masses of lymphoid tissue containing macrophages and lymphocytes (primarily T lymphocytes).
Splenectomy
Immune response decreased to encapsulated bacteria (Streptococcus pneumoniae, neisseria meningitis)
Lymph nodes
-Primary site for the first encounter between antigen and lymphocytes
Hematopoiesis
- Blood cell production-occurring in liver and spleen of the fetus and bone marrow after birth
- Carry out functions such as O2, immunity, and tissue remodeling.
- Erythrocytes and granulocytes generally differentiate fully before entering the blood
- Extramedullary hematopoeisis-blood cell production from spleen, liver, adrenal glands, lymph nodes, adipose tissue, kidneys-usually sign of disease (pernicious anemia, sickle cell, thalassemia, certain leukemias
- Occurs in the bone marrow and stem cell pool
Bone marrow
- Adults have two kinds of bone marrow-Red marrow (active or hematopoietic marrow-also called myeloid tissue)
- Yellow marrow (inactive marrow)
- Active marrow found in pelvis, flat bones, vertebrae, cranium and mandible, sternum and ribs, humerus and femur.
Stem cells
- Hematopoietic stem cells-progenitors of all hematologic cells
- Mesenchymal stem cells (MSCs) are stromal cells and have a role in maintaining HSCs-These can differentiate into a variety of cells including osteoblasts (produce bone), adipocytes (store fats), and chrondrocytes (produce cartilage).
- Hematologic compartment of the bone marrow consists of a variety of cellular and molecular microenvironments called niches.
Erythropoiesis
- Development of RBC’s in the bone marrow.
- Proerythroblasts have ribosomes can produce protein, differentiates through several intermediate forms of erythroblast while synthesizing hemoglobin
Reticulocyte
- Last immature form of an erythroblast (an annucleate and meshlike-reticular network of rRNA.
- It matures into an erythocyte within 24-48 hours.
- Reticulocyte count is useful in clinical index of erythopoietic activity and indicates whether new red cells are being produced
Regulation of Erythopoiesis
-In issues with tissue hypoxia erythropoietin is secreted by the liver and peritubular cells of the kidneys.
-Body responds to reduced oxygenation in two ways
1-Stimulation of chemoreceptors of the carotid and aortic arch that signals the brain to increase oxygen intake through increased ventilation
2-Stimulation of receptors on the kidney peritubular cells to increase erythropoietin synthesis and release, thus increasing the oxygen-carrying capacity of the blood
-Chronic renal failure and lack of erythopoiesis
Hemoglobin
- Oxygen-carrying protein of the erythrocyte, packed blood cells take up O2 in the lungs and exchange for carbon dioxide in the tissues.
- Without reactivation of methohemoglobin (Fe++ containing hgb) cannot bind oxygen. Certain drugs and chemicals such as nitrates and sulfonamides can reduce the oxygen carrying capacity.
CO (Carbon Monixide)
-small amount of CO directly competes with hemoglobin/oxygen. this will decrease hgb ability to bind with oxygen and transport.
NO (Nitric Oxide)
- Can bind with ferrous ion and hemoglobin may shed a small amount when releasing oxygen-thus causing blood vessels to dilate help oxygen gain access to the tissues.
- Produced by the blood vessels
Nutrition and erythropoesis
-Lack of B12 (cobalamin), folate (folic acid), B6, riboflavin, pantothenic acid, niacin, ascorbic acid, and vitamin E is necessary for this process
B12
large molecule that requires protein secreted by parietal cells in the stomach (intrinsic factor IF) for transport across the ileum. Once absorbed B12 is stored in the liver and used as needed in erythropoiesis
Destruction of the RBC
- After about 100-120 days in circulation, old RBC’s are removed by tissue macrophages-primarily in the spleen
- Conditions causing accelerated RBC destruction increase the load of bilirubin for hepatic clearance, leading to increased serum levels of unconjugated bilirubin and increased urinary excretion of urobilirubin. Gallstones (cholelithiasis) can result from a chronically elevated rate of bilirubin excretion
Iron Cycle
- Iron for hgb production is carried by transferrin to the bone marrow where it binds to transferrin receptors on erythroblasts
- Splenic red pulp macrophages are specalized for iron recycling with increased expression of proteins for uptake of hgb
Hepcidin
-regulates iron levels and synthesized in the liver.
Development of leukocytes
- consists of lymphocytes, granulocytes, and monocytes.
- Hematopoietic stem cells differentiate into two populations: lymphoid progenitors and myeloid progenitors.
- Lymphoid progenitors that remain in bone marrow undergo differentiation into the B-cell lineage and mature in lymphoid organs
- Common myeloid progenitors further differentiate into progenitors for basophils, mast cells, eosinophils, and megakaryocytes and into granulocytes/monocyte progenitors
- The granulocyte/monocyte proginetors further differentiate into monocytes/marcophages, neutrophils,
Leukocyte production
-Increases in response to infection, to the presence of steroids, reduction or depletion of reserves in to marrow. It’s also associated w/ strenous activity, convulsive seizures, heat, intense radiation, paroxysmal tachycardias, pain, nausea and vomiting and anxiety
Development of platelets
- aka thrombocytes-derived from stem cells and progenitor cells that differentiate into megakaryocytes
- 2/3 of platelets enter circulation and other 1/3 remain in the splenic pool.
- During inflammation IL-6 induces increased synthesis of TPO (thrombopoietin-hormonal growth factor) which increases production of newly formed platelets which are more thrombogenic.
Hemostasis
-arrest of bleeding by formation of a blood clot
-Sequence of events:
1-vascular injury leads to to arteriolar vasoconstriction to limit blood flow
2-damage to endothelial cell lining of vessel exposes prothrombogenic subendothelial-leading to platelet adherance, activation to form a plug
3-tissue factor-activates clotting (coagulation) system to form fibrin clots to prevent further bleeding
4-the fibrin/platelet clot contracts to form a permanent plug and fibrinolysis to limit the size of the plug.
NO, cGMP, PGI2
- vasodilatotrs that work with endothelin (vasoconstrictor) to modulate blood flow and pressure.
- inhibit platelet adhesion and aggregation
Platelet adhesion
Mostly mediated by the binding of the platelet surface receptor to von willebrand factor (vWF)
Blood clot
-Strands are made of fibrin which is produced by the coagulation system
Clotting system
- Clotting system is presented as two pathways of initiation: Extrinsic (aka tissue factor pathway), and intrinsic (contact activation pathway or plasma kallikrein-kinin)
- These pathways join in a common pathway with activation of factor x, which proceeds with thrombinm fibrin, and clot formation-these pathways are controlled by anticoagulation proteins
Extrinsic pathway
activated when there’s vascular injury and blood escapes into tissue with activation of tissue factor
Intrinsic pathway
not significant pathway for normal hemostasis but is a pathophysiologic surface defense mechanism against foreign proteins, microbial pathogens, and artificial materials
-Those with deficiencies in intrinsic pathway components (i.e factor XI, XII) don’t have disruption of hemostasis or prolonged bleeding with the exception of hemophilia C
Lysis of blood clots
primary system breakdown of clots is the fibrinolytic system (plasminogen-plasmin system)
- tpa and upa both used in breakdown of clots
- Products of fibrinolysis include fibrin degradation products -being d dimer
- Measurements of d dimer has been used for dx of DVT or PE
Erythrocytes (RBC)-disorders
altered erythropoiesis, anemias, hemorrhage, hodgkin disease, leukemia
Erythrocytes (MCV-size of RBC)-Disorders
Anemias, thalassemias
Erythrocytes (hematocrit determination)-disorders
hct-percentage of a given volume of blood that’s occupied by erythrocytes
-Hemorrhage, polycythemia, erythrocytosis, anemias, leukemia
Hemoglobin metabolism (Serum ferritin determination)
(Depletion of body iron)
-Iron deficiency anemias
DIC
involves bleeding disorders of bleeding time, platelet count, fibrinogen,
-Thrombocytopenia, an elevated PTT, PT, increased d-dimer, and decreasing fibrinogen,
Hematopoiesis has two stages
- Proliferation
- Maturation
Iron cycle
- reutilizes iron released from old or damaged erythrocytes
- Iron binds to transferrin in the blood is transported to macrophages of the MPS
- Then stored in the cytoplasm as ferritin
Iron homeostasis
- controlled by hepcidin
- Small hormone produced by hepatocytes
Precusor cells
- Hematopoiesis or blood cell formation takes place in red bone marrow and further differentiated in lymph tissues
- All blood cells originate from undiferentiated stem cells
- Which then give rise of proerythroblasts, megakaryoblasts, myeloblast, lymphoblasts and monoblasts
- Proerythroblasts: erythrocytes-red blood cells
- Megakaryoblasts-megakaryocytes-platelets
- myeloblast-neutrophils, basophils, eosinophils
- lymphoblasts-agranulocytes which are lymphocytes
- monoblasts-agranulocytes-monocytes
Hemostasis part 2
- Vascular spasm (lesson blood loss)
- Platelet plug formation (sticky platelets release chemicals attracting more plt to area-plt plug)
- coagulation (plasma already contains prothrombin and fibrinogen clotting factors)
- -prothrombin turns into active form thrombin
- -thrombin turns fibrinogen into active form fibrin
- -Fibrin-fine threads forming a mesh-stable clot
