CCNM: Physiology 1: hematology and CBC Flashcards
Note - pages 35 - 42 description of basic cell molecule (i.e. mitochondria)
Molecular motors: (some basic info)
Kinesin - move to (+) end of microtubule
Dynein - move to (-) end of microtubule
Myosin - binds to actin in muscle production motion
- Connections that are STRUCTURAL
- Connections that PERMIT ION/MOLECULAR TRANSFER
Refer to figure2-8
Cellular Adhesion Molecules (CAMs): allow cells to bind to BM and each other
Integrins - cell to cell & cell to BM (basal membrane), bind to receptors
IgG superfamily - membrane bound immunoglobins
Cadherins - calcium dependent molecules that mediate cell to cell adhesion
Selectins - lectin-like binding domains that bind carbs
Aka zonula occludens
Surround APICAL margin of epithelial cells
Permit passage of some small molecules and ions between cells: Paracellular pathway
Prevent movement of cellular proteins
Ridges composed mostly of: occludin, claudin, and JAMs (junctional adhesion molecule)
Disruption is associated with changes in intercellular permeability of tight junction
i.e. infectious diarrhea, renal disorders, dermatological disorders, BBB disruption
Located basal to tight junctions
Aka belt desmosome
Function: Associate cell skeletons of adjacent cells, therefore structurally link cells for stability
Function: anchor basal surface of cells to basal lamina (like sticky shoes)
Focal adhesions are similar but, but much more dynamic
-assist in cellular movement
-provide info to cell about extra cellular matrix (ECM)
-proteins assemble/disassemble regularly
-6 from each cell
Each unit called a connexin, 6 connexins = connexon
Function: Allows for intercellular communication (yay), and passage of ions/small molecules between cells without having to enter ECM (like living in residence… You can go from home to school without even stepping outside)
-RBCs are fast flowing and WBCs (leukocytes) roll along the endothelial cells nice and slow
-P-selectins on endothelial cells interact with PSGL -1on leukocyte
* leukocytes are able to roll because existing interactions are broken and new ones form
-Oh no, inflammation!
-Inflamed endothelial cells: 1 upregulate P-selectins (increases p-selectin-PGSL-1 interactions therefore neutrophil slows even more) and 2 secrete IL-8 which remain at the periphery of these cells
-IL-8 on endothelial cell binds with chemokine receptor (Rc) on leukocyte. This causes a cascade of signalling, initaiated by a G-protein associated with chemokine Rc, within the leukocyte.
-This activates the integrin - conformational change in integrin allows for binding with iCAM on inflamed endothelial cell. These strong interactions allow leukocyte to fully adhere to cell surface.
-integrin signalling and chemokine exposure cause a reorganization of leukocyte cytoskeleton and a change in cell morphology.
The leukocyte can now insert itself between two endothelial cells and squeeze through to the surrounding inflamed connective tissue. This is called Transendothelial Migration.
- Message transmission, 2. local or general and 3. specificity depends on:
GAP JUNCTION: cell to cell, local and anatomical location
SYNAPTIC: across synaptic cleft, local, and anatomical location AND Rc
AUTOCRINE/PARACRINE: by diffusion in interstitial tissue, local, and Rc
ENDOCRINE: by circulating body fluids, general and Rc
Describe the four main types of Receptors:
A) Channel-linked Rc - signal binds and causes conformational change that allows it to open/close
B) Enzyme-linked Rc - same as above but instead of open/close, it activates enzyme and generates a product
C) G-protein coupled Rc -signal binds to Rc and g-protein binds to Rc, g- protein gets activated
D) intercellular Rc - signal diffuses through cell membrane and binds to Rc, and activates it
Describe the our main ways that receptors are regulated:
Regulation of gating in ion channels:
A) Ligand-gated channels open in response to ligand binding
B) Phosphorylation-gated channels: protein phosphorylation or dephosphorylation regulate opening/closing
C) Voltage-gated: changes in membrane potential alter channel openings
D) Stretch or pressure-gated: mechanical stretch of the membranes result in channel openings
Na, K ATPase:
Catalyzes the hydrolysis of ATP to ADP and uses the energy to extrude 3 Na+ from the cell and take two K+ in the cell for each ATP molecule hydrolyzed.
An electrogenic pump: Three (+) charges out of the cell for two (+) charges that go in the cell
A coupling ratio of 3:2
Calcium Handling in Mammalian Cells
Where is Calcium stored in the cell?
How does it enter the cell?
How is it transported out of the cell?
Stored in the endoplasmic reticulum and to a lesser extent the mitochondria
Enters the cell via LIGAND-GATED channels, VOLTAGE-GATED channels, and store operated calcium channels (SOCCs)
Exits the cell via Ca, Mg ATPases, Ca,H ATPases and Na,Ca antiport
Note: in the cell, Calcium binds to Calcium binding proteins (CaBP) that bring about various effects
G-Protein - common way to translate a signal to a biological effect
Heterotrimeric G Protein…. A summary
Ligand binds to G protein coupled receptor (on membrane) –>
GTP replaces GDP on alpha subunit–>
GTP-Alpha separates from beta-gamma and both subunits activate various effectors–>
Produce physiological effects
Intrinsic GTPase activity of GTP-alpha then converts GTP to GDP and then alpha, beta and gamma all reunite.
Figure 2-26 - release of IP3 and DAG as secondary messengers
- Ligand binds to G-protein coupled Rc and activates phospholipase C (PLC) or activation of intracellular protein kinases will activate PLC
- activated PLC will result in hydrolysis of PIP2 –> this produces DAG and IP3
- IP3 releases Calcium from ER where it will bind to CaBP and cause physiological effects
- DAG activates protein kinase C (PKC) which will cause physiological effects
- a membrane bound protein
- converts ATP to cAMP
- stimulatory ligands bind to stimulatory Rc and activates adenylyl cyclase via Gs G-protein
- inhibitory ligands Bind inhibitory Rc and inhibit adenylyl cyclase via Gi G-protein
- made from ATP by Adenylyl cyclase
- broken down into AMP (inactive form) by phosphodiesterase
- cAMP activates PKA
- PKA phosphorylates proteins –> producing physiological effects
92% - Water
7% - Proteins
1% - Nutrient and waste products (amino acids, vitamins, glucose, oxygen, carbon dioxide, nitrogenous waste and trace elements - note these are not bound to anything, just dissolved in plasma fluid
Interstitial fluid = plasma - proteins
- albumin - carrier protein - good indicator of liver function
- Fibrinogen - clotting material
- Transferrin - transfers ions
- Ferritin - iron storage (mostly in liver)
- globulins - ie immunoglobulins (IgG)
Name the plasma proteins and their function.
Note most are made in the liver
Albumin - carrier protein - best indicator of liver function
Fibrinogen - clotting material
Transferrin - transfers ions
Ferritin - storages iron (mainly in liver)
Globulins - ie immunoglobulins (IgG)
What is oncotic pressure?
Oncotic pressure - water pulled out of interstitial fluid into capillaries due to the presence of plasma proteins.
Clinical significance! Liver/kidney disease and malnutrition result in decreased plasma proteins therefore less water is being pulled into vessels (decrease in oncotic pressure) –> leads to edema (too much water in interstitial fluid)