Normal Physiology

1. Transport Across Cell Membrane

2. 2
1. Cell Cytoskeleton—Filament and Tubular Structures
= G1
2. Functional System of Cells
 Endocytosis –Ingestion by the cell = G2
 Synthesis of cellular structures by Endoplasmic
Reticulum and Golgi Apparatus = G3
3. Locomotion of cell = G4
Reading Task and Presentation (5 mins)

3. Recall
• Endocytosis
• Pinocytosis
• Phagocytosis
• Autophagy
• Autophagosomes
• Clathrin
• Actin and Myosin
• Opsonisation
• Bactericidal agents of Lysosomes
• Lysozyme
• Lysoferrin
• Acid at a pH of about 5.
• Lysosomes and Regression of Tissues and Autolysis of
Damaged Cells

4. Recall
• Most common type of movement in human body is_______________
• Ameboid Movements
• Pseudopodium
• Receptor Proteins
• Actin & Myosin
• Types of cells exhibiting Ameboid Movements
• WBCs
• Cancer cells; Sarcomas
• Control of Ameboid Movements
• Chemotaxis
• Chemotactic Substance
• Positive & Negative Chemotaxis
• Cilia and Ciliary Movements
• Two types of Cilia
• Motile and Non-motile
• Motile
• Respiratory Pathway
• Fallopian tubes
• Flagellum of sperm; HOWEVER????

5. Recall
• Non-Motile = Primary Cilia
• Sensory antennae.
• Epithelial cells  Flow Sensors
• Defect in primary cilia in renal epithelial cells
• Polycystic kidney disease
• Mechanism
• First  Axoneme
• Second Can still beat under appropriate conditions, even after removal of
cell membrane or destruction of elements other than Axoneme.
• Third  Two conditions are necessary
• Energy: ATP
• Appropriate Ionic conditions
• Fourth  Movement Characteristic.
• Fifth  Dynein = ATPase

6. Recall
• Endoplasmic Reticulum Function
• 000000000
• 000000000
• 000000000
• Golgi Apparatus Function
• 000000000
• 000000000
• 000000000
• Mitochondrial Extraction of Energy from Nutrients
• 000000000
• 000000000
• 000000000

7. Simple Diffusion
Carrier-Mediated Transport
includes facilitated diffusion and primary and secondary active
transport
Facilitated Diffusion
Primary Active Transport
Secondary Active Transport
Osmosis
Overview: Transport Across Cell Membrane

8. Characteristics
NOT-carrier mediated.
Down an electrochemical gradient (“downhill”).
Passive
Does NOT require Energy.
Simple Diffusion

9. Can be measured????
Simple Diffusion
The minus sign:
Preceding the diffusion equation indicates that the
direction of flux, or flow, is from high to low
concentration. It can be ignored if the higher
concentration is called C1 and the lower concentration
is called C2.

10. What is Permeability?
P in the equation for diffusion.
ease with which a solute diffuses through a membrane.
characteristics of the solute and the membrane.
 Factors that increase permeability:
↑ Oil/water partition coefficient
↓ Radius (size) of the solute
↓ Membrane thickness
Simple Diffusion

11. Permeability
Small hydrophobic solutes have the highest permeabilities in lipid
membrane. E.g.______________
Hydrophilic solutes must cross cell membranes through water-filled
channels, or pores, or via transporters. E.g.______________
If the solute is an ion (is charged), then its flux will depend on both
the concentration difference and the potential difference across
the membrane.
Simple Diffusion
O2 and CO2
Na, Ca, and K

12. Permeability
Simple Diffusion
O2 and CO2  Easily Pass Thru (Simple Diffusion?)
Solute (Charged Ion)  Concentration and Charge Differenc
Na, Ca, and K (Ions)  Need Channels, Pores or Transporters

13. Includes / has 3 types:
Facilitated Diffusion
Primary Active Transport
Secondary Active Transport
Carrier Mediated Transport

14. Characteristics:
Stereo-specificity
Saturation
Competition
Carrier Mediated Transport

15. Stereo-specificity
D-glucose (the natural isomer) is transported by facilitated
diffusion, but the L-isomer is not.
Simple diffusion, in contrast, would not distinguish between the
two isomers because it does not involve a carrier.
Carrier Mediated Transport

16. Saturation
Transport rate increases as the concentration of the solute
increases, until the carriers are saturated.
Transport maximum (Tm) is analogous to the maximum
velocity (Vmax) in enzyme kinetics.
Carrier Mediated Transport

17. Competition
Structurally related solutes compete for transport sites on
carrier molecules.
Galactose is a competitive inhibitor of glucose transport in
the small intestine.
Because?
Carrier Mediated Transport

20. Characteristics:
Down an electrochemical gradient (“downhill”), similar to simple
diffusion.
Passive
More rapid than simple diffusion.
Carrier mediated; exhibits stereospecificity, saturation, and
competition.
Facilitated Diffusion

21. Examples:
1. Na+, K+-ATPase (or Na–K pump) in Cell Membrane.
Both Na and K are transported against their electrochemical
gradients.
 Energy; ATP.
 Usual Stoichiometry is 3Na+/2K+
 Specific inhibitors
 Digitalis
Primary Active Transport

23. Examples:
2. Ca2-ATPase (or Ca2+ pump) in Sarcoplasmic Reticulum
 Sarcoplasmic reticulum (SR) or cell membranes transports
Ca2+ against an electrochemical gradient in myocytes.
 Sarcoplasmic and endoplasmic reticulum Ca2+-ATPase is called
SERCA.
Primary Active Transport

25. Examples:
3. H+, K+-ATPase (or Proton pump) in Stomach Lumen
 Gastric parietal cells transports H+ into the lumen of the
stomach against its electrochemical gradient.
 Inhibited by proton pump inhibitors, such as omeprazole
(Risek).
Primary Active Transport

26. Carrier Mediated Transport

28. Characteristics:
Transport of Two or More solutes is coupled.
One of the solutes (usually Na+) is transported “Downhill” and
provides energy for the “Uphill” transport of the other solute(s).
Energy is NOT provided directly BUT INDIRECTLY from the
GRADIENT that is maintained across cell membranes.
Secondary Active Transport

29. Characteristics:
Same direction across the cell membrane, it is called Co-transport
or Sym-port. E.g.,
Na-Glucose Co-transport in small intestine and renal early
proximal tubule.
Na–K–2Cl– Co-transport in the renal thick ascending limb.
Opposite directions across the cell membranes, it is called
Counter-transport, exchange, or Anti-port.
Na-Ca2 Exchange and Na–H Exchange.
Secondary Active Transport

30. Examples:
1. Na–Glucose CO-Transport
Carrier for Na–Glucose cotransport
In the luminal membrane of intestinal mucosal
Renal proximal tubule cells.
Glucose is transported “uphill”; Na+ is transported “downhill.”
Energy is derived from the “downhill” movement of Na+.
Secondary Active Transport

31. Examples:
2. Na–Ca COUNTER-Transport
Many cell membranes contain
Ca2+ “uphill” from low intracellular Ca2+ to high extracellular
Ca2.
Ca2+ and Na+ move in opposite directions across the cell
membrane.
The energy is derived from the “downhill” movement of Na+.
Secondary Active Transport

32. Carrier Mediated Transport

34. Secondary Active
Transport
 Are Different Carrier Mediated Transports Possible in a
Single Cell?
 Where is more glucose and where is more Na?

35. Secondary Active
Transport
Where is more glucose and where is more Na?

37. Characteristics:
Flow of water (Solvent) across a semipermeable membrane
Low Solute Conc.  High Solute Con.
Osmosis
Osmosis = Only allows Solvent molecules to move freely,
Diffusion = Allows Both Solvent and Solute molecules to move freely.

38. Examples:
Osmosis

39. Calculating Osmotic Pressure (Van’t Hoff’s law):
Osmotic pressure
Osmosis
Osmotic pressure depends on the concentration of
osmotically active particles.

40. Osmotic pressure increases when the solute concentration increases.
A solution of 1M CaCl2 has a higher osmotic pressure than a solution of
1M KCl because the concentration of particles is higher.
The higher the osmotic pressure of a solution, the greater the water flow
into it.
Osmosis

41. Osmotic pressure increases when the solute concentration increases.
Isotonic
Hypertonic
Hypotonic
Colloid osmotic pressure, or oncotic pressure
Osmosis
Same osmotic Pressure
Solution with higher osmotic Pressure
Lower osmotic pressure
Q: How to make IL Normal Saline?
Q: What is the conc. of Na and Cl in Normal Saline Solution?
Q: How to make Hypertonic Saline?

42. Calculating effective osmotic pressure
Reflection coefficient (σ)
What is Osmotic Pressure?
What are Isotonic, hypertonic and hypotonic solutions? What happens
to RBCs in them?
Osmosis Reading Task

43. Reflection coefficient (σ)
Ease with which a solute permeates a membrane.
Number between zero and one.
One = Impermeable = Albumin  Creates osmotic pressure
Zero = Permeable = Urea  Ineffective Osmole.
Number between zero and one.
Osmosis
Q: What is Ineffective Osmole?
A: An ineffective osmole will contribute to total plasma osmolality but because it can freely
move from the ECF to ICF, it generates no oncotic pressure.

44. Effective Osmotic Pressure
(Osmotic Pressure X Reflection Co-efficient)
If Reflection Co-efficient = 1  Maximal Effective Pressure
If Reflection Co-efficient = 0  NO Effective Pressure
Osmosis

45. Tight Junctions:
Gap Junctions:
Anchoring Junctions:
Cell Junctions

46. Cell Junctions

47. s
Cell Junctions

48. Intercellular Connections Communicating vs. Connexin
Occluding vs. Claudin/occludin
Anchoring/Adherens vs. Cadherin

49. Cell Junctions

50. Cell Junctions

51. Cell Junctions

52. Tight Junctions (zonula occludens):
Attachment between cells (often epithelial cells).
 may be “tight” (impermeable), as in the renal distal tubule, or “leaky”
(permeable), as in the renal proximal tubule and gallbladder.
may be an intercellular pathway for solutes, depending on the size, charge,
and characteristics of the tight junction.
Cell Junctions

53. Gap Junctions:
are the attachments between cells that permit intercellular communication.
permit current flow and electrical coupling between myocardial cells.
are the location of gap-junction channels that provide pathways for
communication between adjacent cells.
many areas (including muscle and nervous tissue), but abundant in some
epithelia.
Connexins
Cell Junctions

55. What is the importance of Gap Junctions?
What are Hormones?
Paracrines?
Autocrine?
Exosomes?
miRNA
Intercellular Connections
Reading Task and Presentation (5 mins)
G1

56. Channels
Catalytic Receptors
G-Protein Coupled Receptors
Intracellular receptors and Tissue Remodeling.
Intracellular Signalling
G2
G2
G3
G4
Reading Task and Presentation (5 mins)