Blood and lymphoid tissue Flashcards
Albumin
Carrier protein
Stays in blood stream
Hydrophilic
Where do RBCs come from?
Reticulocytes
How do RBCs develop?
Cells in kidney can measure O2 in blood and will initiate erythropoiesis
Erythropoiesis
- Form reticulocyte in bone marrow
- Released into blood stream to mature
What are leukocytes made from?
Progenitor cells
Lymphoid progenitors
Differentiate into lymphocytes and released in bloodstream
Fully mature in lymphoid organs
What are the lymphoid organs?
Thymus, spleen
Myeloid progenitors
Differentiate into other WBCs
Monocytes released into blood stream and mature
Granulocytes mature in bone marrow
- Some immature ones are reserved in bone marrow and activated/released when needed
What are platelets formed from?
Megakaryocytes
Stimulated by thrombopoietin
Stages of hemostasis
- Vessel spasm to control blood loss
- Formation of platelet plug
- Requires vWF
- Fibrinogen
- vWF binds to subendothelial portion of blood vessel
- Hooks grab the platelets
- Fibrinogen binds to 2B3A receptor on platelet and binds one to the next
- Fibrin fills holes between - Coagulation cascade
Coagulation cascade
Prothrombin -> thrombin
Thrombin converts fibrinogen -> fibrin
What is the intrinsic pathway stimulated by?
Blood injury
- Slower
What influences the intrinsic pathway?
Heparin
What is the extrinsic pathway stimulated by?
Tissue factor released by endothelial cells in response to injury or inflammatory process
- Faster
What influences the extrinsic pathway?
Coumadin
What should you check to evaluate the extrinsic pathway?
Prothrombin time
What should you check to evaluate the intrinsic pathway?
Partial thromboplastin time
What enzyme is important for clotting?
Ca++
What regulates coagulation?
Antithrombin III
Protein C
Protein S
What does Antithrombin III do?
Inactivates coagulation factors and thrombin
What does Protein C do?
Inactivates factors V and VIII
What does Protein S do?
Accelerates Protein C
Clot dissolution
Fibrinolysis causes plasminogen -> plasmin
- Digests fibrin strands
- Digests several clotting factors
What does TPA do?
Medication that speeds up plasminogen to dissolve blood clots
What is primary thrombocytosis?
An abnormally high level of free thrombopoietin due to abnormal thrombopoietin receptors on platelets
What is secondary thrombocytosis?
Increased production of thrombopoietin due to tissue damage
What is the job of thrombopoietin?
Regulate how many platelets one has
What happens when there’s an excess of thrombopoietin?
It will go into bone marrow and have it make more platelets, but abnormal receptors means there’s an excess of platelets and increased risk of developing a clot
What is Factor V Leiden mutation?
Factor V cannot be inactivated by Protein C
- Venous thrombosis
- Keeps stimulating coagulation cascade
Prothrombin gene mutation
Elevated prothrombin levels
- Venous thrombosis 3x greater than normal
What does Factor V do?
Factor V stimulates coagulation cascade
What does MI cause?
Venous congestion
Ventricle can’t squeeze effectively, leading backup of blood
How do hyper-estrogenic states/hormone based contraceptives affect clotting?
Increase synthesis of clotting factors
Reduce synthesis of Antithrombin III
What is Thrombocytopenia?
Reduced number of platelets
- Decreased production or survival
What is heparin-induced thrombocytopenia?
Reduction in platelets stimulated by heparin
Immune reaction against heparin-platelet factor 4 complex
Immune complexes activate platelets and leads to thrombosis
- Platelets release particles that activate thrombin
What does HIT lead to?
Thrombocytopenia due to overuse of platelets
What is Immune thrombocytopenic purpura?
Autoimmune disorder where antibodies are created against 2B3A receptors
What happens in ITP?
Circulating immune complexes around platelet are created
More susceptible to phagocytosis and removal by spleen
What does ITP lead to?
Drop of platelet count
What is thrombotic thrombocytopenia purpura?
A deficiency of the enzyme that breaks down wVF
What happens in TTP?
Platelets adhere and aggregate
What is impaired platelet function?
Decreased activity of COX pathway
Decreased production of prostaglandin
Decreased production of thromboxane
Decreased platelet aggregation
How do NSAIDs affect the COX pathway?
COX pathway is blocked
What does the COX pathway produce?
Prostaglandins, which get converted into thromboxane
What does the lipoxygenase pathway produce?
Leukotrienes
What is Hemophilia A?
Coagulation factor deficiency
Genetic factor VIII deficiency
Can’t wind up with end factor of fibrin
What is Hemophilia B?
Coagulation factor deficiency
Genetic factor IX deficiency
Can’t make fibring
What is Von Willebrand disease?
Coagulation factor deficiency
Genetic deficiency or defect in vWF
Platelets cannot adhere to subendocardial membrane
What is liver failure’s role in bleeding disorders?
Clotting factors are synthesized by the liver
Results in reduction of clotting factors
No clotting factors -> no coagulation cascade -> no fibrin
What is disseminated intravascular coagulation?
Widespread coagulation and bleeding
What is DIC caused by?
Endothelial damage
What happens in DIC?
Widespread activation of coagulation response
Massive clot formation consumes all coagulation proteins and platelets
Hemorrhage follows
Pt initially clots and is followed by a risk of bleeding because the body uses all of its stores of platelets, fibrin, fibrinogen, etc
What is hemolysis?
Premature destruction of RBC
Where does hemolysis occur?
Can occur within or outside blood vessels
What is sickle cell anemia?
Inherited abnormality in hemoglobin S synthesis
What happens in sickle cell?
Deoxygenation and dehydration causes calls to sickle
Hemolysis and vascular occlusion occur
What is Thalessemias?
Genetic disorder of hemoglobin synthesis
What happens in Thalessemias?
Alpha or Beta chain deficiency
Results in small, pale cells
In which population is Alpha-Thalessemia more common?
Asians, Africans
In which population is Beta-Thalessemia more common?
Greeks and Italians, Africans
What is Vitamin B12’s role in blood tissue?
Essential for DNA synthesis and nuclear maturation
Binds to intrinsic factor in the stomach, travels to intestine, is absorbed and used
Normally binds to intrinsic factor
What happens after a Vit B12 deficiency?
Causes large cells due to excessive cytoplasmic growth
Short life span
What is folic acid’s role in DNA and RBC?
Required for DNA synthesis and maturation
How does one acquire a folic acid deficiency?
Reheating food
Drugs that interfere with absorption (seizure disorder drugs)
What are the main branches of WBCs?
Lymphoid line (B and T cells) Myeloid line (all other WBCs)
How does one get neutropenia?
Congenital
Acquired - SLE and RA
- Produce autoantibodies that target antibodies
Infection-/drug-related
What happens in mono?
Virus binds to receptors on B lymphocytes
Virus kills host or incorporates into DNA
Produces easily detectable antibodies
What is a malignant lymphoma?
Solid tumor composed of lymphocytes
What is non-hodgkin lymphoma?
B (more common) or T cell neoplasms
Originate and lymph nodes and can spread
Remission in 60-80% of cases with chemo
How does non-hodgkin lymphoma manifest?
Swollen, painless nodes
Constitutional symptoms
What is hodgkin lymphoma?
Specialized form of lymphoma
What cell rules hodgkin lymphoma?
Reed-Sternberg cells
In which populations is Hodgkin lymphoma more common?
People <40 and >55
How does hodgkin lymphoma manifest?
Painless enlargement of single nodes or group
Usually above diaphragm
Progressive spreading
Constitutional symptoms
5-year cure rate of 85% with radiation and chemo
Hodgkin lymphoma
Arises from single node or chain of nodes Localized to head, neck, mediastinum Orderly spread to contiguous nodes Extranodal involvement is rare Reed-Sternberg cell
Non-Hodgkin’s lymphoma
May originate in extranodal site
More peripheral
Spread not often contiguous
Extranodal involvement is common
What is leukemia?
Blood borne disorder
What are characteristics of acute leukemia
From progenitor cells (less differentiated)
Sudden onset
Bone marrow crowds faster
What are characteristics of chronic leukemia
Fully differentiated cells
Slow progression
No sudden bone marrow crowding
What are characteristics of myeloblastic leukemia
Originating in myeloid (neutrophils) line
What are characteristics of lymphoblastic leukemia
Originating in lymphoid (B&T cells) line
Acute lymphoblastic leukemia
Most common in children
Fast, bone-marrow crowding, progenitor cells, B and T cells
Causes anemia, neutropenia, and thrombocytopenia
More cells in blood stream -> more viscous
Acute Myeloblastic Leukemia
Most common adult leukemia
Fast, bone marrow crowding, progenitor cells, neutrophils
Bone marrow keeps spitting out new WBC into blood stream -> viscous
Increased numbers of undifferentiated blast cells, which crowd the marrow
Chronic Lymphoblastic Leukemia
Slow, more fully differentiated, no bone marrow crowding, B and T cells affected
More common in older adults
Malignancy of B lymphocytes
Progressive infiltration of bone marrow and lymphoid tissues by neoplastic lymphocytes
Lymphocytosis noted on labs
Lymphadenopathy
Poor production of plasma calls -> v gamma globulinemia
Chronic Myeloblastic Leukemia
Slow, more fully differentiated cells, no bone marrow crowding, neutrophils
Results in excessive production of marrow granulocytes and other blood cell precursors
Splenomegaly
Immature WBCs released into blood stream
Which leukemia contains the Philadelphia chromosome?
Chronic Myeloblastic Leukemia
What is multiple myeloma?
B-cell malignancy of terminally differentiated plasma cells
Proliferation of malignant plasma cells in bone marrow
Hyperviscosity of blood
What happens in multiple myeloma?
Abnormal plasma cells secrete cytokines that activate osteoclasts -> bone resorption (punch lesions) -> ^ calcium in blood
What is the Bence Jones protein associated with?
Diagnosing multiple myeloma
