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Day 6 b -P5bCONTROL OF ICF VOLUME (8f) 2.pptx
- 1. DR.HAMISI MKINDI,MD. TO DOWNLOAD CONTACT: hermyc@live.com
- 3. Most cells need a constant cell volume to maintain optimum function
- 4. Cells face constant challenges to their volume either through changes •In Intracellular solute content or •Extracellular osmolality.
- 5. Cells will shrink or swell in response to changes in ICF or ECF tonicity accordingly
- 7. To maintain optimal cell volume animal cells have mechanism to •Accumulate osmotically active molecules •Extrude osmotically active molecules •AS NEEDS BE
- 8. The processes by which swollen or shrunken cells return to normal volume •Are collectively respectively termed •Regulatory Volume Decrease (RVD) or •Regulatory Volume Increase (RVI).
- 10. Cells respond to volume distresses • By activating membrane transport and/or metabolic processes • That result in net solute loss or gain
- 11. Net solute loss or gain returns cell volume to its normal resting state •These processes are essential for normal cell function and survival.
- 12. Cell Volume Regulatory machinery consists of: •An envisaged cell volume sensor •An intracellular signaling cascade •Volume sensitive transporters
- 13. ICVF ICFV SENSITIVE TRANSPORTERS ELEMENTS OF CONTROL SYSTEMS
- 14. The mechanisms can be superficially divided into •Steady-state cell volume regulation •Fast (acute) cell volume regulation •Slow adaptation to chronic changes in osmolarity
- 15. Under steady-state conditions ICFV regulation is mainly due •The Na+-K+ ATPase pump. •This counters the Gibbs-Donnan Effect
- 16. GIBBS DONNAN EFFECT Cells contain a significant concentration of proteins and organic phosphates •These anions cannot cross the cell membrane. •They attract into the cell positively charged particles like Na+ & K+
- 18. Because of of the presence in the cell of impermeant anions •Donnan forces will lead to cell swelling and cell lysis.
- 19. Cell swelling and lysis is avoided because: •Active Na+ extrusion via the Na+-K+-ATPase •Renders plasma membrane effectively impermeable to Na+
- 20. Sodium is actively excluded from the cell by Na-K-ATPase Pump
- 21. If the sodium-potassium pump is inhibited cells would swell
- 22. Inhibition of the pump causes the cell to swell Normal Cell Volume with an intact pump
- 23. When cells are stressed by a change in ECF tonicity • They minimize any change in cell volume • Because cells able to lose or gain solute
- 24. Most cells have capacity for •Easing acute volume perturbations •By changing ICF solute content
- 25. Animal cells have the necessary mechanism to rapidly GAIN or LOSE • Osmotically active molecules: • Primarily inorganic ions such as Na+, K+, Cl−
- 26. “fast” volume regulation is achieved by rapid activation of membrane ion transporters.
- 27. After acute shrinkage, cell volume is regulated In the short term by •A gain of solute (principally Na+ and Cl-) from ECF •Mediated primarily by Na+/H+ exchange, Na+-K+-2Cl− cotransport, and Na+ channels.
- 28. Volume 67% Volume 100%
- 29. In most animal cells, regulatory volume decrease (RVD) occurs through •Loss of potassium and chloride •Via activation of separate K+ and Cl− channels •Or by activation of the K-Cl cotransporter.
- 30. Volume regulatory electrolyte loss is mediated by changes in the activity of membrane channels
- 31. With chronic changes in ECF osmolarity the cells either •Generate extra “idiogenic” solute •Reduce generation of “idiogenic” osmoles
- 32. With chronic cell shrinkage cells secrete organic osmoles (idiogenic osmoles) Taurine, glycine, glutamine, sorbitol and inositol.
- 33. The production of idiogenic osmoles can also be down-regulated to adjust for chronic hypotonic states
- 35. In cell volume regulation mechanism, "volume sensors" are thought to be involved.
- 36. The mechanisms by which cell volume sensed , and •How this signal is transmitted to regulate the activity of effector proteins •Are still incompletely understood.
- 37. Volume sensing mechanisms appear to be extremely sensitive. •Cells can sense and respond to volume changes of less than 3%.
- 38. Changes in membrane tension. through tether forces
- 40. THANK YOU
Editor's Notes
- The slide shows the effects of different concentrations of impermeant solutes in the extracellular fluid on cell volume. If a cell is placed in an isotonic fluid the cells will not shrink or swell. If a cell is placed into a hypotonic solution water will diffuse into the cell, causing it to swell; If the cell is placed in a hypertonic solution water will flow out of the cell into the extracellular fluid and the cell will shrink.
- Depending on the cell type cell shrinkage activates different types of solute uptake mechanisms. In many types of cells, shrinkage activates the ubiquitous a Na-H exchanger. In addition to mediating increased uptake of Na+, extrusion of H+ alkalinizes the cell and consequently activates Cl-HCO3 exchange. The net effect is thus the entry of Na and Cl . The resulting increase in intracellular osmoles then draws water into the cell to restore cell volume toward normal. Alternatively, the RVI response may be mediated by activation of the NKCC1 isoform of the Na/K/Cl cotransporter.
- This slide shows RVD mechanisms following cell swelling. Many cell types respond to swelling by activating solute efflux pathways to decrease cell solute and water content. Depending on the cell type, swelling activates different types of solute efflux mechanisms. In many types of cells, swelling activates Cl− or K+ channels (or both). Activating these channels causes a net efflux of K+ and Cl−, which lowers the intracellular solute content and causes water to flow out of the cell. The result is restoration of cell volume toward normal. Alternatively, the RVD response may be initiated by activating the K/Cl cotransporter.