physio Heme/Onc Flashcards
What are the 3 main functions of blood?
Transport, regulation, and protection
How does blood work to transport?
Delivering O2 and nutrients to body cells
Transporting metabolic wastes to lungs and kidneys for elimination
Transporting hormones from endocrine organs to target organs
How does blood work to regulate?
Maintaining body temperature by absorbing and distributing heat, normal pH using buffers, alkaline reserve of bicarbonate ions, adequate fluid volume in circulatory system
How does blood work to protect?
Preventing blood loss with plasma proteins and platelets in the blood initiate clot formation
Preventing infection through agents of immunity are carried in blood
- Antibodies
- Complement proteins
- WBCs
What are the different components of blood?
Plasma: 55% of whole blood and is the least dense compennt, liquid.
Buffy Coat: Leukocytes and platelets are less than 1% of whole blood
Erythrocytes: 45% of whole blood (hematocrit) and is the most dense component
Which component of blood is the majority of protein found? What protein is most abundant?
It is in the plasma and albumin is the most abundant protein in the blood and it functions as a carrier of other molecules and helps contribute to oncotic pressure
Why is blood considered a connective tissue and what is it’s pH?
7.35-7.45
What are the formed elements of blood?
Buffy coat and erythrocytes
What are erythrocytes and how are they inloved in the blood?
Aka red blood cells. Biconcave disc under normal conditions. They are filled with 2 beta globin chains and 2 alpha globin chains and within them are the four heme groups that bind to oxygen and give the blood the red color. The heme groups each contain iron as well.
Define Oxyhemoglobin
When hemoglobin binds to oxygen, it is called oxyhemoglobin. When O2 loading in the lungs
Define Deoxyhemoglobin
O2 unloading in the tissues
Define Carbaminohemoglobin
20% of CO2 in the blood binds to Hb for transport back to the lungs
What is hematopoiesis?
Formation of blood cells in the bone marrow. The bone marrow produces a hematopoietic stem cell that is influenced by hormone and growth factor to differentiate into either a myeloid progenitor cell or a lymphoid progenitor cell
What is Leukopoiesis?
The formation of WBCs is mediated by Interleukins and colony-stimulating factors (CSFs) are named for WBC type they stimulate (ex: granulocyte-CSF stimulates granulocytes)
What are interleukins?
They are chemical units and help stimulate leukopoiesis
What are clinical significances of colony-stimulating factors?
When we treat cancer patients with chemo, we wipe out these bone marrow cells. So we will inject them with CSFs called gGSF to help stimulate this entire process of hematopoiesis and leukopoiesis. Brand names are sometimes referred to as Filgrastim or Neupogen.
What is the process of red blood cell formation called?
erythropoiesis
Why are reticulocyte counts important?
It indicates the rate of RBC formation and can be extremely helpful in patients that have anemia or sickle cell disease
What is released to help stimulate erythropoiesis?
Erythropoietin or EPO from the kidneys. In instances of reduced oxygen, whether that be in sickness or when you’re climbing Mt. Everest, the kidneys will stimulate the release of erythropoietin for the body to make more blood. This is sometimes done in athletes, they will inject themselves with EPO to improve stamina and oxygen capacity. It can increase the hematocrit number up to 60%, but it can be very dangerous and has an increased risk of clotting
How else can the body control erythropoiesis?
Through our diet. Amino acids, lipids, and carbohydrates are needed to support RBC formation.
What is the most important molecule needed for the formation of hemoglobin?
Iron. 65% of the iron in our body is found on hemoglobin, the rest sits in the liver or spleen.
How is iron transported in the body?
The iron in our body is stored as ferritin and transported through the body on transferrin. TIBC (total iron binding capacity) is the ability of the ferritin (iron) to bind to transferrin.
What kinds of foods provide iron?
Red meat, drak greens, legumes, whole grains, raisins, blackstrap, Molasses, seeds
What two types of vitamins are necessary for DNA synthesis?
B12 and Folate
How are erythrocytes broken down?
The heme component is broken down into bilirubin (a yellow pigment) and bilirubin is secreted from the liver as bile into the intestines and the degraded into urobilinogen and then this is turned into sterobilin which then exits the body through the feces.
The globin chains are then synthesized into amino acids and then realised into the circulation
What are the responsibilities and categories of leukocytes?
When will we see leukocytosis clinically?
In response to infection, there are also changes in the amounts of leukocytes based on the type of infection
What is the mnemonic to remember the decreasing abundance of leukocytes in the blood?
Never Let Monkeys Eat Bananas
Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils
What do we know about our granulocytes?
Our neutrophils, eosinophils, and basophils are mostly phagocytic. They are more short lived.
What is the responsibility of neutrophils?
Most numerous WBCs (50-70%). Granules contain either hydrolytic enzymes or antimicrobial proteins, defensins
Very phagocytic and are referred to as “bacteria slayers”. Kill microbes by process called respiratory burst (which is when the cell synthesizes potent oxidizing substances (bleach or hydrogen peroxide)
Defensin granules merge with phagosomes that form “spears” that pierce holes in the membrane of the ingested microbe
What is the responsibility of Eosinophils?
Account for 2-4%. Red-staining granules contain digestive enzymes that are release enzymes on large parasitic worms, digesting their surface. They also play role in allergies and asthma, as well as immune response mediators
What is the responsibility of basophils?
Rarest WBC, 0.5-1% of leukocytes. Large, purplish black (basophilic) granuales contain histamine.
Histamine: inflammatory chemical that acts as vasodilator and attracts WBCs to inflamed sites. Are functionally similar to mast cells
What is the responsibility of lymphocytes?
Second most numerous WBC, accounts for 25%. Mostly found in lymphoid tissue (example: lymph nodes, spleen), but a few circulate in blood
Crucial to the process of immunity and there are two types
T lymphocytes (T cells): act against virus-infected cells and tumor cells (mature in the thymus)
B lymphocytes (B cells): give rise to plasma cells which produce antibodies that mature in the bone marrow
What’s the responsibility of Monocytes?
Largest of all leukocytes (3-8%). U shaped or kidney shaped nuclei. Leave the circulation, enter tissues, and differentiate into macrophages. Actively phagocytic cells, crucial against viruses, intracellular bacterial parasites, and chronic infections. Active lymphocytes to mount an immune response
What is the process of platelet formations?
The hematopoietic stem cells (hemocytoblast) becomes a megakaryoblast/cyte which eventually is broken up into platelets.
What are the components of platelets?
Contain several chemicals involved in the clotting process: serotonin, calcium, enzyme, ADP, platelet-derived growth factor.
What keeps platelets inactive?
Platelets are circulating throughout the body and are kept really inactive and mobile through Nitric oxide (NO) and postacyclin, these released from other cell linings in the body.
How does thrombopoietin work?
Platelet cell formation is regulated by thrombopoietin, which is a hormone produced by the liver.
How is thrombopoietin clinically significant?
Thrombocytopenia is a huge indicator of liver failure and esophageal varices, where the veins enlarge. If the veins rupture, the patient can die. In people with liver failure, we use this as an indicator of their true platelet count.
How is the liver so involved in the blood?
The liver filters blood, makes all clotting factors, anticoagulants, anf fibrinolytics. So the liver is critical to hemostasis and stoppoing of bleeding
What is step 1 of hemostasis?
Initially starts with vascular spasm, which means we have constriction to reduce blood flow to an area that has been injured.
How is step 1 of hemostasis triggered?
Direct injury to the smooth muscle and epithelial cells. Levels of NO and prostacyclin will slow down because we want clotting to occur and will be activated. Collagen fibers are exposed and attract platelets
What is step 2 and 3 of hemostasis?
Platelets like to stick to the exposed collagen fibers via von Willbrand Factor (vWF), which stabilizes platelet and collagen adhesion
After platelets attach to collagen fibers via vWF in steps 2 and 3, what other chemicals do platelets release?
platelets attached are then activated to release ADP, Thromboxane A2, and Serotonin to recruit more platelets and decrease blood flow to the area.
In addition to recruiting more platelets, what do Thromboxane A2 and Serotonin do?
Slow down vascular spasm
Where do aspirin and clopoidogrel (antiplatelet drugs) work in this system?
They inhibit ADP, Thromboaxne A2, and serotonin from being released and accumulating more platelets
Hemostasis is an example of what feedback mechanism?
Positive
What is step 4 of hemostasis?
This is the coagulation phase of blood clotting where Fibrinogen is turned into a fibrin mesh to work to seal off the damaged area, which is the final stage.
What is the coagulation cascade?
Extrinsic: tissue factor
Intrinsic: collagen and triggering of cascade
What is factor XIII also called?
The fibrin stabilizing factor
After time, and the clot is no longer needed and we need to start the healing process, what does that look like?
The fibrin mesh is pulled further together at the site of contraction to bring the skin back together, called clot retraction.
How is clot retraction facilitated?
The platelets that are here and bound to this will release platelet-derived growth factor (PDGF) to stimulate the division of smooth muscle cells and fibroblasts to help rebuild blood vessels.
What role does VEGF play in angiogenesis?
Vasucular endothelial growth factor (VEGF) stimulates a process called angiogenesis, which stimulates the process of secretions of red blood cells and a lot of the endothelial lining of the blood vessels and some of the skin.
How is VEGF being used right now as a target of cancer therapies?
It helps build new build vessels, so researchers are looking into VEGF as a way to see if we can stop the growth of cancerous cells
What is the process of fibrinolysis?
This is a mechanism that regulates clot growth. So it is the breakdown of clots naturally in our body. This is why we dont have crazy over clotting.
What is the main protein in the process of fibrinolysis?
Plasminogen is a plasma protein that is trapped in a clot, and is converted to plasmin, a fibrin-digetsing enzyme. Tissue plasminogen activator (tPA), factor XII, and thrombin all play a role in conversion of plasminogen to plasmin.
What is tPA and how is it used clinically?
Tissue Plasminogen Activator is a clot buster and can be pushed if someone comes in suffering from a stroke. It is a very dangerous med
How do Heparin and Protein C work during fibrinolysis?
Heparin can be made in our own blood from basophils and mast cells that stimulate the production of antithrombin III to remove thrombin and prevent further creation of these blood clots. Protein C (with cofactor protein S) inactive factor V and VIII
Where do coumadin and apixaban work here?
They just prevent this fibrinolysis from continuing forward
When a patient comes in with a hemoglobin less than 7, most often due to a GI bleed, we are going to order alot of tests and a GI consult, but what else are you going to order?
A TYPE AND SCREEN FIRST in preparation to give the patient a blood transfusion. We will transfuse packed Red blood cells.
RBC membranes bear many different antigens.
What happens if someone receives the wrong blood?
Mismatched transfused blood is perceived as foreign and may agglutinated and destroyed and could lead a potentially fatal reaction
How are ABO blood groups developed?
Based on the presence or absence of two agglutinogens (A and B) on surface of RBCs
Type A has only A agglutinogen (on the surface off the cell, make opposite antibody)
Type B has only B agglutinogen
Type AB has both agglutinogen
Type O has neither agglutinogen
What are agglutinins?
Blood may contain performed anti-A or anti-B antibodies. They act against transfused ABO antigens not present on recipient’s RBCs
What pertains to the donor and what pertains to the recipient?
Red blood cell type: donor
Antibodies in plasma: recipient
What is the Rh group?
+= present D antigen (85% Americans)
Anti-Rh antibodies are not spontaneously formed in Rh- individuals.
How are Rh groups most important clinically?
Anti-Rh antibodies form if an Rh- individual receives Rh+ blood or an Rh- mom is carrying a Rh+ fetus.
Pregnancy and childbirth like Mom-Jenn is O- but had Grace who is A+ and had to receive Rhogam injections for her second pregnancy, Meredith who was also +, so her immune system did not attack the fetus
What are some special circumstances in relation to Rh group reactions and childhood?
If someone has a miscarriage and they get pregnant a second time, the same reaction could still occur.
