Cellular Physiology & Hematology Flashcards
What are integrins?
Large family of CAMs involved in cell-cell and cell-BM adhesion.
What is the IgG superfamily?
Membrane bound immunoglobulins.
What are cadherins?
Calcium dependent CAMs
What are selectins?
Lectin-like binding domains (bind sugar moieties).
What are the 2 types of intercellular connections?
1) structural connections
2) connection that permits ion/molecular transfer
What is another name for Tight Junctions?
Zonula occludens
What is a tight junction composed of?
Occludin, Claudin, JAMs and typically surrounds the apical margin of epithelial cells.
What types of molecules do tight junctions allow to pass?
Some ions and small molecule can pass between cells between tight junctions (para cellular pathway)
Tight junctions also prevent the movement of cellular proteins
-also BBB disruption, renal disorders, and dermatological conditions like psoriasis.
What is another name for zonula adherens?
Belt desmosomes
What is the function of zonula adherens?
Functions to associate cell skeletons of adjacent cells. Along with spot desmosomes, they function to structurally link cells for stability.
What is the function of hemidesmosomes?
To anchor the basal surface of cells to the basal lamina
- functions like sticky shoes
- focal adhesions are similar but they are much more dynamic
- protein assembly/disassemble regularly
- assist in cellular movement
- provide information to cell on conditions of ECM
Describe the configuration of gap junctions.
Dodecameric channels (12) Each unit is called a connexin 6 connexins = 1 connexon Allow for intercellular communication (electrical activity) and passage of ions/small molecules without entering the ECF
What are 4 types of receptors?
1) channel-linked
2) enzyme-linked receptors
3) G-protein-coupled receptors
4) intracellular receptors
What are the steps in channel linked receptor binding?
Signal binds, channel opens, ions flow across membrane
Describe the steps in enzyme linked receptor binding.
Signal binds, enzyme activated, enzyme generates product
Describe the steps in GPCR binding.
Signal binds, G protein binds, G protein gets activated
Describe the steps in intracellular receptor binding.
Signal binds, activated receptor regulates Tc
What are 4 ways of receptor regulation?
1) ligand-gated
2) phosphorylation-gated
3) voltage-gated
4) stretch or pressure-gated
Describe the steps of Ca2+ recruitment from the ER through GPCR binding.
Binding of ligand to GPCR activates PLC which hydrolyzes PIP2 to IP3 and DAG.
IP3 goes on to release Ca2+ from the ER and DAG activates PKC.
Calcium released from the ER bind to CaBP and then goes on to elicit its physiological effects.
Describe the cAMP activation system.
Ligand binds to GPCR, GP swaps put GDP for GTP on the alpha subunit which goes on to activate adenylyl cyclase. Adenylyl cyclase catalyzes the conversion of ATP to cAMP, which then activates PKA, which goes on to phosphorylate proteins and cause physiological effects
Where are most plasma proteins made?
Liver
What are the 5 main plasma points?
Albumin Fibrinogen Transferrin Ferritin Globulins
What is the function of albumin?
Carrier protein
What is the function of fibrinogen?
Clotting material
What is the function of transferrin?
Transfers iron
What is the function of ferritin?
Stores iron (mostly in liver)
What is the function of globulins?
Immunoglobulins
What is oncotic pressure?
Water pulled out of the ISF into capillaries due to presence of plasma proteins
What type of cells do platelets come from?
Megakaryocytes
What signal regulates megakaryocyte development?
Thrombopoetin
What is thrombocytopenia?
Decrease in platelet production - cancer, chemo, viral infection of marrow
Increase in platelet destruction - autoimmune, inflammation, reaction to meds.
What are the 4 components of a platelet membrane?
Von Willebrand factors
Fibrinogen
ADP
Thomboxane A2
What are the 5 components found in platelet granules?
Serotonin ADP Clotting factors PDGF (platelet devised growth factor) PAF (platelet activating factor)
What happens what there is damage to the epithelium?
1) collagen is exposed
2) tissue factor is released from damaged epithelial cells
What is secreted from healthy endothelium in order to keep platelets inactive while their are in circulation?
Prostacyclin
What shape are platelets when they are in their inactive form?
Smooth discoid shape
What is the initial activation of platelets?
A break in the endothelium
What signal/compounds further activate platelets (there are 3)?
ADP
TXA2
Thrombin (from previously activated platelets)
What compound does thrombin activate?
It converts fibrinogen to fibrin
What is the role of the vWF receptors in platelet activation?
Binds to vWF leading to platelets adhering to exposed collagen.
What is the role of the glycoprotein receptor in platelet activation?
It binds fibrinogen causing platelets to stick to each other
What induces the release of vWF?
Exposure to collagen
What is the role of serotonin in platelet function?
Serotonin is secreted in response to platelet activation and functions in platelet aggregation.
Also, serotonin is a vasoconstrictor
What is then source of ADP in platelets?
Secreted from platelet mitochondria in response to platelet activation and thrombin
What is the function of ADP in platelet activation?
Platelet aggregation
What is the source of PAF?
Platelets, neutrophils, and monocytes secrete PAF in response to platelet activation.
What is the source of thromboxane A2?
Comes from phospholipids in the platelet membrane in response to PAF
What is the function of PDGF?
To promote would healing by attracting fibroblasts and smooth muscle cells
What is the main activator of the intrinsic coagulation pathway?
Exposed collagen
What is the main activator of the extrinsic coagulation pathway?
Tissue factor (III)
What factor of the coagulation pathway converts prothrombin to thrombin?
Factor X (10)
What converts fibrinogen to fibrin?
Thrombin
What is plasminogen called once it is in its activated form?
Plasmin
Where is plasmin found once it is activated?
Embedded within the clot (along with fibrin and platelets)
What is the function of plasmin?
It is secreted slowly by the endothelium to restore the integrity of the blood vessel.
What two compounds activate plasmin?
Thrombin and tPA (Tissue types plasminogen activator)
What acute disease would tPA be administered for in the Emergency Room?
Myocardial Infarction
What is the source of plasminogen and plasmin?
They are secreted from the liver and plasma in response to tPA and thrombin
What is the role of plasminogen/plasmin?
To dissolve fibrin and fibrinogen
What is the function of NSAIDs?
They inhibit the COX enzyme that promotes the synthesis of thromboxane A2
What is the effect of NSAIDs on coagulation?
Shuts down coagulation
What is the effect of heparin when administered into the system?
Heparin activates antithrombin III which inactivates thrombin, and factors IX, X, XI, XII
What is the effect of heparin on coagulation?
Heparin decreases coagulation
What is the effect of Warfarin when administered to the system?
Warfarin blocks vitamin K, which is a co-factor in the synthesis of calcium-dependent clotting factors II, VII, IX, X.
What is the effect of warfarin on coagulation?
Warfarin decreases coagulation
Where are leukocytes produced?
Bone marrow
