A&P II-Lecture-Chapter 19
Function of monocytes
-4-8% of total leukocytes -very actively phagocitic -mature into macrophages in tissues
How are platelets formed?
-start as hematopoietic stem cells -precursor cells, megakaryoblasts, derive from myeloid cell line -they become megakaryocytes (massive cell with multiple copies of DNA located in single nucleus) W thrombopoietin, mature megakaryocytes extend their ribbon-like arms and reach into clefts of bone marrow sinusoids into blood stream
Erythrocyte death in spleen (explain stages)
1. erythrocytes become trapped in the sinosoids of the spleen 2. spleen macrophages digest erythrocytes 3. Hemoglobin is broken down into amino acids, iron ions, and bilirubin 4a. iron ions and amino acids are recycled and used to make new hemoglobin in red bone marrow (transferrin- protein used to transfer ion ions through the blood) 4b. at same time 4a is occurring, bilirubin enters the blood and is transported to the liver, where it is modified and excreted in feces and urine.
What are the 5 steps of HEMOSTASIS
1. vascular spasm 2. platelet plug formation 3. coagulation 4. clot retraction 5. thrombolysis
Lifespan of erythrocyte
100-120 days
Cirrhosis of the liver often reduces production of many types of plasma proteins, including albumin and clotting factors. Predict the effects on the body of decreased numbers of these proteins in the plasma. Would this also affect the number of y-globulins in the plasma? Why or why not?
A decrease in albumin will result in a decrease in osmotic pressure and a resulting loss of water from blood vessels into the interstitial fluid. A decrease in clotting proteins will interfere with the bloods ability to clot and may prolong bleeding time when an injury occurs, Cirrhosis will nto affect the production of y-globulins, as they are produced by B lymphocytes, NOT the liver.
Predict the effect of decreased albumin levels in the plasma
A decreased amt of ALBUMIN in plasma will decrease its colloid osmotic pressure. As result, less water will be drawn into capillaries at venous end of the capillary bed, leading to a net loss of more water than normal from the plasma. The water lost to the interstitial fluid will accumulate there, resulting in edema.
Explain why a person with blood type O- can donate to someone with any blood type, but can receive blood from only other O- donors.
A person with type O- blood has no A, B, or Rh antigens on the surface of the erythrocytes, and so there can be no reaction with a recipient's anti-A, anti-B, or anti-Rh antibodies if given to a recipient. However, this person's plasma contains anti-A, anti-B, and possibly anti-Rh antibodies, which would react with any blood type donated, other than O-.
A person with Type AB- can receive blood from which blood types?
A-, B-, AB-, O- (those without Rh sensitized blood types)
A sample reacts with anti-A and anti-B antibodies, but does not react with anti-Rh antibodies. What is the blood type?
AB-
Least people have which blood type?
AB-
A person with Type AB- can be a donor to which blood types?
AB- and AB+
Two antigen groups that have particular importance in clinical setting
ABO blood group and Rh blood group
What are the 4 main categories of plasma proteins
ALBUMIN-maintains osmotic pressure IMMUNE PROTEINS- produced by leukocytes; function in immunity TRANSPORT PROTEINS-ind and transport hydrophobic compounds through the blood CLOTTING PROTEINS-stop blood loss from damaged vessels
Which of the following plasma proteins is responsible for osmotic pressure? A. Y-GLOBULINS B. ALBUMIN C. A-GLOBULINS D. CLOTTING PROTEINS
B. Albumin
granulocytes
BEN (all derivatives of myeloid cell line) Basophils Eosinophils Neutrophils
What are common causes of bleeding disorders?
Bleeding disorders often result from clotting protein deficiencies.
CLOT RETRACTION
Bringing edges of wound closer together, much as sutures do with edges of a skin wound. Clot retraction also sqeezes serum--a fluid consisting of plasma minus the clotting proteins--out of the clot. **IN ADDITION to forming a more compact clot, mitotic stimulants, PLATELET-DERIVED GROWTH FACTOR (PDGF) will stimulate cell turnover/repair
Which of the following is not a formed element of blood? A. ERYTHROCYTE B. LEUKOCYTE C. MAST CELL D. PLATELET
C. MAST CELL
What would happen without antithrombin-III?
Clots would develop and be unsuppressed, leading to potentially large and obtrusive clotting in the vessel.
Overall goals of intrinsic and extrinsic pathways
Creation of Factor X (Xa) Creation of Thrombin And at last, the creation of Fibrin
Which of the following is not an anticlotting agent produced by endothelial cells? A. prostacyclin B. protein C C. Antithrombin-III D. Warfarin
D. Warfarin
The anticoagulation drug warfarin primarily disrupts the extrinsic coagulation pathway. Explain why disrupting only this pathway disrupts the entire coagulation cascade
Disrupting either the intrinsic or extrinsic pathway leads to disruption of teh entire process because both pathways rly heavily on each other to proceed to completion. In addition, the extrinsic pathway is the MOST IMPORTANT path to the production of factor Xa, which is required for the common pathway.
function of eosinophils
Eosinophils-account for fewer than 3% of total leukocytes in the blood -stain red; cytoplasm -involved with body's response to infection with parasitic worms and in allergic reactions (i.e. asthma)
Predict the homeostatic consequences of extensive blood loss due to injury. (How does blood normally help maintain homeostasis?)
Extensive blood loss impairs the ability of blood to carry out its homeostatic functions. This will disrupt gas exchange, solute distribution, the volume of extracellular fluid and cytosol, the body's acid-base balance, and blood pressure.
True or false: Erythrocytes are biconcave discs with prominent nuclei
False, no nuclei
How does blood regulate temperature and acid-base homeostasis in the body?
Heat=byproduct of many chemical reactions in the body, particularly metabolic reactions. Blood carries heat away from actively metabolizing tissue, which helps maintain a constant temp. in the tissue
What is the process of erythrocyte development
Hematopoietic stem cell (cell can become any type of formed element in this state) -->myeloid cell line -->ECFU/Proerythroblast (CELL IS NOW COMMITTED to becoming erythrocyte, this step requires the hormone erythropoietin from chemoreceptors in kidneys; when they detect low oxygen levels hormone is released!!) -->Early erythroblast (hemoglobin is synthesized rapidly -->Late erythroblast (nucleus shrinks and is ejected from cell -->Reticulocyte (remaining organelles ejected and cell enters bloodstream) -->Erythrocyte (now matured)
All leukocytes are derived from
Hematopoietic stem cells (HSC)
Prostaglandin and ibuprofin, how do they relate?
Ibuprofin can suppress prostaglandin response (inflammation, fever, pain) but it can also lead to an increased risk of blood clots
What role does blood play in the immune system and the blood clotting?
Immune system- both the cells (leukocytes) and proteins of the immune system use the blood as a transport vehicle to reach almost any tissue in the body Platelets and certain proteins form a BLOOD CLOT that seals a damaged vessel, preventing excessive blood loss
Difference between intrinsic and extrinsic pathway
Intrinsic pathway is slower to form fibrin but yeilds MORE Extrinsic pathway is quicker to form fibrin but yeilds LESS
Hemophilia B
Is caused by a shortage of factor IX
Hemophilia A
Is caused by a shortage of factor VIII
what happens if spleen is no longer present in body? where do rbc's go to die
LIVER or SINUSOIDS OF RED BONE MARROW
Function of lymphocytes
Lymphocytes (from lymphoid cell line)- two types (T cells and B cells) all together make up 30-40% of lymphocytes in the blood, contain large spherical nuclei T cells- migrate to the thymus in the medinastinum to complete their maturation, activates all components of the immune response (cellular immunity) and destroys virally infected and cancer cells B cells- remain and mature in the bone marrow, mature into plasma cells which secrete antibodies when activated to attack/attach to pathogens
Agranulocytes
Lymphocytes and monocytes
Platelets are derived from cells called what?
Megakaryocytes
Certain chemotherapy drugs for cancer inhibit cell division. How will this affect the size and structure of a megakaryocyte? Predict how this will influence platelet formation
Megakaryocytes undergo repeated rounds of mitosis to become cells with a large cytoplasmic mass. If their mitosis is inhibited, they will be much smaller cells (and fewer in number), resulting in decreased levels of platelets.
Mr. Jones, whose blood is type A-, has been injured and requires a blood transfusion. His friend, Mr. Ramirez, wants to donate blood to Mr. Jones. Mr. Ramirez's blood type is AB+. Can he donate to Mr. Jones? Explain.
Mr. Ramirez cannot donate blood to Mr. Jones. With blood type A-, Mr. Jones has anti-B antibodies and possibly anti-Rh antibodies in his plasma ( if he has been exposed to Rh+ blood previously). These antibodies will bind to the B and Rh antigens of Mr. Ramirez's blood.
A blood sample from your patient shows that she has decreased numbers of neutrophils. Predict the effects of this condition. How would it differ if number of T lymphocytes were decreased instead?
Neutrophils are very active phagocytes, particularly in response to a bacterial infection. A deficiency in neutrophils will make a patient especially at risk for bacterial infections. T lymphocytes are involved in directly killing virally infected cells and cancer cells, but they are also responsible for activating other cells and components of the immune system. With a decrease in T lymphocytes, a patient is at risk for all types of infectious agents and certain cancers.
Most people have which blood type?
O+ (38%)
What are the other components of blood plasma?
Other solutes include (make up 1% of plasma volume): Glucose, amino acids-Function in nutrition, used for protein synthesis Ions-electrolyte and acid-base homeostasis Dissolved gasses (small amounts of oxygen and carbon dioxide)-oxygen delivered to the tissues; carbon dioxide delivered to the lungs to be exhaled) Wastes-delivered to the appropriate organ for excretion
percentages of centrifuged blood
PLASMA (water, plasma proteins, small solute)- 55% BUFFY COAT (platelets, leukocytes)-1% ERYTHROCYTES (RBC count, also known as hematocrit)-44%
Anticlot medications
Patients with thrombi or emboli are given anticoagulants, HEPARIN and WARFARIN Heparin-used to manage and prevent emboli (ONSET IS IMMEDIATE; GOOD IN CASE OF IMMEDIATE NEED) Warfarin-used in OUTPATIENT SETTINGS, ingested by mouth and so takes a bit longer to activate desired degradation of clotting; GOOD FOR LESS IMMEDIATE DESIRED RESULTS Two can be used at same time; Careful monitoring that patient is neither over-nor under-anticoagulated ASPRIN- USED/ACTS DIRECTLY ON PLATELETS; inhibits enzymes that activate platelet aggregation
examples of decreased HEMATOCRIT level-induced anemia (3)
Pernicious anemia- b12 deficiency leading to interference in DNA SYNTHESIS of hematopoietic stem cells in Red Bone Marrow Hemolytic anemia- erythrocyte DESTRUCTION, caused by bacterial infection, immune system and liver diseases, or lead poisioning Aplastic anemia-when red bone marrow STOPS PRODUCING ERYTHROCYTES, induced by ionizing radiation or certain medications, CAUSE UNKNOWN
Mr. Jackson presents to the emergency room with a minor wound that has bled for several days. An examination of his medical history reveals that Mr. jackson has hemophilia A, which is caused by a deficiency of factor VIII. Your co-worker suggests that you give Mr. jackson some platelets to stop the bleeding. Will this help the patient? Why or why not?
Platelets won't help Mr. Jackson, as he is unable to form a platelet plug. He has a deficiency in a clotting factor, which prevents coagulation. This means that fibrin will not be produced ad the platelet plug will not be "glued" together. Giving him platelets will only increase the size of the ineffectual platelet plug.
What would happen without prostaglandin?
Platelets would aggregate and form unwanted clots, and there would be no inflammatory response to damaged tissue, high risk of blood clots, stroke, etc.
hormonal supplementation for cortisol deficiency
Prednisone (ex of corticosteroid + immunosuppressant)
How does prostacyclin regulate hemostasis?
Prostacyclin inhibits the FIRST AND SECOND stages of clot formation: they do so by INHIBITING platelet aggregation, and TRIGGERING inflammation
Explain why proteins can readily travel through plasma, but lipids cannot
Proteins are composed of largely polar amino acids (although some have non-polar R groups) and therefore mix with polar water. Lipids are composed largely of NONPOLAR hydrocarbons and therefore do not mix with polar water. Instead, lipids congregate, forming a clump in the blood, which could block blood flow. For this reason, they must be transported through the blood on plasma proteins.
How are bleeding disorders treated?
Replacement of the missing clotting protein or factor with continual periodic transfusions
Ms.Wright also wants donate to Mr. Jones (A-). Her blood type is O+. Can she donate to Mr. Jones? Explain.
She can donate to Mr. Jones SO LONG AS HE HAS NOT BEEN PREVIOUSLY EXPOSED TO Rh ANTIGENS. If he has been previously exposed to Rh antigens, there will be anti-Rh antibodies in his plasma which will bind to the antigens of new donor blood from Ms. Wright.
example of abnormal HEMOGLOBIN-induced anemia (1)
Sickle-cell disease- those with only one defective gene are asymptomatic but are immune to malaria -two sickle-celled patients produce abnormal hemoglobin, Hemoglibin S or HbS -WHEN BLOOD LEVELS ARE LOW, HbS proteins line up in a row forcing the erythrocytes into a sickle shape. These sickled cells get stuck in capillary beds where diameter is smallest, leading to ischema and tissue damage. -These cells are eventually destroyed due to their inflexible nature, and as result lower the Complete Blood Count's hematocrit levels inducing anemia
The venom of certain snakes contains substances that activate factors V, IX, and X. Predict the effects of these substances would have on human blood
The activation of these three factors will stimulate coagulation, causing the blood to begin to clot abnormally.
What happens if someone is missing active Protein C (or is lacking Protein S, a required protein to activate Protein C)?
Their body would not be able to catalyze the reactions that degrade factors Va and VIII.
Snake venom can also contain substances that activate protein C and directly inhibit thrombin. Predict the effects these substances would have on human blood. How do these effects differ from those in the previous question?
These substances will have the oppose effects of those in the previous question--they will inhibit coagulation and lead to abnormal bleeding.
Are non-polar hormones hydrophilic or hydrophobic?
They are hydrophobic, examples include aldosterone and cortisol
What would happen if someone were deficient of heparan sulfate?
They wouldn't receive amplification/catalyzation of antithrombin-III, leading to a slower process of Xa and thrombin repression (more clot forms)
Many toxins and poisons interfere with a cell's ability to undergo protein synthesis. Will this affect platelets that are already in the bloodstream? Why or why not?
This will not affect platelets that have already formed, which lack nuclei and other organelles required for protein synthesis. It will, however, effect the formation of new platelets via thrombopoiesis
What is thrombosis, and what may cause it?
Thrombosis is a hypercoaguable condition which can result in the formation of an inappropriate clot -when a clot forms at an improper time and tissue location -Can be caused by prolonged immobility, which causes blood to pool and eventually potentially clot, and other conditions increasing risk (surgery, trauma, abnormal clotting factors, anticoagulant deficiencies, and pregnancy)
PLATELET PLUG FORMATION
Triggered by exposure of platelets to collagen (damaged endothelial cells secrete VON WILLEBRAND FACTOR, which makes platelets "sticky") Platelets adhere to rough surface to form a plug
True or false: The main function of erythrocytes is to transport oxygen on the protein hemoglobin
True
Who is the universal RECIPIENT?
Type AB+ (antigens present: A, B, Rh)
Who is the universal DONOR?
Type O- (no antigens)
RBCs are anaerobic because..
Unlike other cells, red blood cells lack mitochondria. As a result, they rely on anaerobic respiration for energy. ... Because erythrocytes lack mitochondria, they also lack the oxidative enzymes that are required for aerobic respiration.
plasminogen is also an example of
a PROENZYME or ZYMOGEN, a protein in an inactive state
Thrombosis
a hypercoaguable condition, caused by the formation of an innapropriate clot -clot is known as THROMBUS -piece of clot is called THROMBOEMBOLUS; these are DANGEROUS!!! These may break off and lodge in smaller vessels downstream from the thrombus, leading to DVT, deep vein thrombosis, and then pulmonary edema.
Function of granulocytes
basophils -make up less than 1% of total leukocytes -stain as deep methane blue granules -chemicals MEDIATE INFLAMMATION
precursor to bilirubin
biliverdin (ex. green pigment in bruise) turns into bilirubin (yellow pigment in bruise)
Which substances does blood transport through the body?
blood transports OXYGEN via heme group, distributes solutes (nutrients, hormones, IONS which regulate ion concentration in tissue ion concentrations, and wastes), leukocytes and immune system proteins, platelets from megakaryocytes, plasma proteins (regulate pH levels between 7.35-7.45),
If antibodies Anti-A, Anti-Rh are in the plasma, then which blood type must be present?
blood type B-
If antibodies Anti-A, Anti-B, and Anti-Rh are present in the plasma, then what blood type must be present?
blood type O-
leukocytes/WBC's
can be granulocytes (contain cytoplasmic granules) or agranulocytes (lacking visible cytoplasmic granules) -they do not "function" within the blood, but use it as a means to transport themselves to the affected tissues, at which point they adhere to the walls of capillaries or venules and exit the blood by squeezing between endothelial cells of the vessels
Leukemias
cancers of blood cells or bone marrow. -Classified as ACUTE or CHRONIC ACUTE LEUKEMIA is characterized as a rapid increase in immature, nonfunctional, or poorly functional blood cells, where as CHRONIC LEUKEMIA is slow accumulation of abnormal and mature leukocytes myelogenous leukemias are granulocyte-leukocytes (B.E.N.) ABNORMAL cells in LEUKEMIA crowd bone marrow, reducing ability to make healthy formed elements. Cancerous cells enter the blood and spread
Bleeding disorders often result from__________
clotting protein deficiencies
COAGULATION
coagulation cascade which results in a common pathway goal (creation of Xa, activated Factor X), and then prothrombin activator acts upon prothrombin and changes it into thrombin Thrombin acts on fibrinogen and changes it into thrombin
VASCULAR SPASM
contraction of the smooth muscle in the wall of a damaged blood vessel to prevent blood loss
anemia
defined as decreased oxygen carrying capacity of the blood has three primary causes: decreased hematocrit levels, decreased hemoglobin, and abnormal hemoglobin
THROMBOLYSIS
destruction of a blood clot -Healed ENDOTHELIAL cells release tPA (tissue plasminogen activator) or a similar enzyme UROKINASE (from kidney and found in plasma of interstitial fluid) -tPA activates plasminogen, found in plasma, and changes it into plasmin -Plasmin degrades fibrin, and the clot dissolves, degrading both fibrin AND fibrinogen, allowing the remaining aspects of clot to dissociate with the endothelium
What causes pulmonary embolism?
emboli break off and lodge deep in the vessels of the lungs, a reaction to deep vein thrombosis DVT
Tissue plasminogen activator, urokinase, and plasmin are important components of?
fibrinolysis (the destruction of fibrin and fibrinogen)
antigens (composition)
found on erythrocytes, biomarkers that directly correlate in name to the blood type (i.e. antigen A is a biomarker indicating that blood type is A, and we can also infer that agglutinins/antibodies present are the opposite AKA anti-B; NO USE OF Rh in example)
Addison's disease
hyposecretion of cortisol and aldosterone
examples of decreased HEMOGLOBIN-induced anemia (2)
iron-deficiency anemia- most common, due to inadequate dietary iron, reduced absorption of iron in digestion, or slow blood-loss (ie menstruationleuk). Iron are needed for function of heme groups and therefore inhibit erythroblasts from creating hemoglobin. Less oxygen is carried throughout the body if there is less available hemoglobin to bind to. Anemia of chronic disease-underlying conditions (cancer) can inhibit the transfer of iron to the red bone marrow CAN ALSO BE DUE TO: malnutrition, B6 deficiency, certain drugs, poisoning with heavy metals such as lead, and pregnancy
Cirrhosis
liver disease; causes include-cancer, alcoholism, viral hepatitis. one consequence of disease is the decrease in production of plasma proteins, particularly ALBUMIN. Lack of ALBUMIN leads to reduction of OSMOTIC PRESSURE, which causes the blood to lose water in the extracellular spaces. This results in excess water in ECF (edema, swelling) in the abdominal area is known as ASCITES. Progressive decline in clotting proteins leads to easy bruising and DELAY in clotting, can be FATAL.
function of neutrophils
neutrophils- most common, make up about 60% total leukocytes in blood -lilac color when stained -attracted to injured cells by chemicals released by damaged cells, a process called CHEMOTAXIS -i.e. trauma described from textbook: "from stepping on a nail, to infection by bacteria" -are phagocytic
how are erythrocytes and hemoglobin recycled
polypeptide chain of hemoglobin breaks down via macrophages in spleen into amino acid, iron ions, and the rest is converted into (first biliverdin; then to) bilirubin. Amino acid and Iron ions recycled/transported to red bone marrow and iron ions recycled via transferrin, a carrier protein that carries it through blood
Regulation of clotting
prostacyclin (PRODUCED BY ENDOTHELIAL CELLS)-is a prostaglandin, a group of chem's with many functions including triggering inflammation, main function in clot regulation is that it inhibits platelet aggregation nitric oxide- produced by endothelial cells, causes vasodilation antithrombin-III (PRODUCED BY LIVER)-MOST IMPORTANT ANTICOAGULANT, binds to and inhibits the activity of both factor Xa and thrombin. Inhibits thrombin already formed and prevents more thrombin from being formed. Heparan sulfate (PRODUCED BY MANY CELL TYPES, AND FOUND IN ECF)-polysaccaride that enhances the activity of Antithrombin-III, SIMILAR TO clinical drug, HEPARIN, in function Protein C (PRODUCED BY LIVER)-Catalyzes the reactions that degrade factors Va and VIIIa. To become active, Protein C needs PROTEIN S!
non-polar hormones can impact ______
protein production
What is the process of leukocyte development
see image
Those with Rh antigens are
sensitized
tell me about spectrin
structural protein in RBC's helps give RBC flexibility to move throughout the vessels with ease during its 100-120 day lifespan
Thrombolytic agents
tPA - sometimes given after a heart attack or stroke to dissolve clot, activates plasminogen to make plasmin (for thrombolysis of clots) Urokinase-made by cells of kidneys, activates plasminogen Plasmin-plasma protein made by liver, degrades fibrin and causes clot dissolution
It is generally recommended that patients who have recieved CPR should NOT be given thrombolytic agents like tPA for SEVERAL DAYS. Explain why this is the case.
tPA activates plasmin, which catalyzes the reactions that degrade fibrin and break up clots in the blood. After CPR, there is GENERALLY SOME AMOUNT OF INTERNAL BLEEDING (due to the trauma caused from CPR) and as a result, blood clots form to help heal the wounds. BUT, if tPA is administered, the clots won't form/will dissolve and the patient will keep bleeding internally.
Complete blood count (definition)
test for anemia and many other conditions -blood is drawn and examined under a microscope to evaluate a number of characteristics of blood cells. -1 erythrocyte count, # of erythrocytes reported as number in cells per mm, USED TO CALC. HEMATOCRIT -2concentration of hemoglobin in sample -3 erythrocyte characteristics (size, volume, concentration of hemogrobin in cytosol, -4 number and volume of platelets
Those without Rh antigens and have never had direct contact with Rh antigens are known as
unsensitized
How are blood types matched for blood transfusions?
we think about the donor's antigens in relation to the recipient's antibodies.
Talk about hemolytic disease of the newborn, Erythroblastosis Fetalis
when an Rh-negative mother carries and gives birth to an Rh-positive fetus -fetal erythrocytes enter the mother's blood, which stimulates her immune system to create anti-Rh antibodies. These antibodies do not attack her first pregnancy, but HER SECOND PREGNANCY is impacted. In her second pregnancy,, Rh antibodies can cross over the placenta and attack the blood of the fetus, where they perform hemolysis on the Rh positive blood. Pregnant women with Rh- blood are given injection of Rho(D) immune globulin, which contains anti-Rh antibodies. These antibodies bind to the fetal cells that have entered the maternal circulation, PREVENTING maternal leukocytes from producing and secreting their own anti-Rh antibodies.