For pc1 students Cell physiology black lion hospital

1. Addis Ababa University
School of Medicine
Department of Medical Physiology
Lecture Notes
on
Cell Physiology and transportation
for
PC I Medical students
1

2. Objectives
• At the end:
– Able to discus the structures of the a cell
– Able to discuses the functions of the structures of a cell
– Able to list the types and functions of membrane proteins
– Able to discus cell transport
– Able to discuses about body fluid
2

3. Cell Physiology
• The human body composed of non-cellular and cellular components
• Non-cellular components
– Water
– Macro -nutrients: carbohydrate, protein, lipid, nucleic acid
– Micro- nutrients: vitamins, electrolytes
• Cells:
 Smallest structural & functional unit of life
 Small in size  10-20um
 Large in number  75-100 trillion
 Arranged in d/f functional structures
3

4. Structural or functional classification
4
Fig1: Cell types

5. Fundamental theories and cell types
 Types
 Eukaryotic
 Blood, nerve, muscle, fat and glandular cells
 Prokaryotic cells
 Bacteria, virus
 Have many functions
 Transportation, Defenses, protection
5

6. Structures of the human cells
1) Plasma/cell membrane
– Double, thin, flexible (fluid mosaic model) structure surrounding animal cell
– Composed of biological macromolecules
• Carbohydrates, proteins, lipids and cholesterol
– Functions:
• Selective barrier (semi-permeable) and transport
• Support, protect the cell & retain cytoplasmic contents
• Recognition (identity proteins)
– Pattern recognition receptors
» Detect molecules on pathogens
• Maintains chemical & electrical gradients
• Communication
• Controls and directs cellular activities
6

7. Major compositions of cell membrane
• Phospholipids (25%)
• Form double membrane, lipid bilayer (outer and inner)
– Asymmetry ( variation in composition and arrangement)
– Amphipathic molecule
» Hydrophilic and hydrophobic properties
• Carbohydrates(3%)
– Combined (glycoprotein and glycolipid): recognition and blood clotting
• E.g Glycocalyx ( blood clotting)
• Proteins (55%): membrane proteins
– Intrinsic and extrinsic
• Cholesterol (13%)
– For immobilization of lipid molecules and give extra support
7

8. Fluid mosaic model of cell membrane
8
The mosaic model states that a membrane is a fluid structure
with a “mosaic” of various proteins embedded in it.
Fibers (collagen) where
cell rest is called basal
lamina
Fig 2: Fluid mosaic model

9. Membrane proteins
i- Integral proteins
– Transmembrane, intrinsic proteins
– Strongly bonded with lipid bilayer
– Not removed easily with out affecting the membrane
– Most of them are glycoproteins
• Receptors (GPCR)
• Ion channels
• Carriers (permease, pumps)
9

10. ii- Peripheral proteins
– Attached to the inner membrane
– Not penetrate the hydrophobic core of the membrane
– Easily removed
– Enzymes
• Protein kinases, Phospholipases
– Important
• Cell signaling
• Anchoring (integral proteins and cytoskeleton)
10
Membrane proteins con’t

11. Membrane proteins con’t
11
Fig 3: Integral and peripheral membrane proteins

12. Functions of membrane proteins: summary
• Receive chemicals and transport substances
– Receptor and transporter proteins
– Transporters proteins (uniport, symport and antiport)
• Link structures: Linkers proteins
• Communication(gap junctions) and recognition (identity)
– Immune cells can recognize self cells
• Enzymatic reaction and signal transduction
• Cell adhesion: one cell to an other
– Platelet attached on endothelial cells
• Connect the cell with the cytoskeleton
• Keeping the integrity of membrane: structural proteins
12

13. Membrane proteins and their functions con’t
13
Fig 4: Functions of membrane proteins

14. Parts of human cell...
2) Cytoplasm
– Space b/n the nucleus and cell membrane
– Contains fluid: cytosol/ICF with d/f compositions and
Suspended structures : organelles (except red cells)
• The machinery of the cells
• Has their own functions
14
Cytoplasm
cytosol
Water, glucose,
proteins, electrolytes
Dispersed
particles
Smaller: FA
Larger: neutral fat,
glycoprotein, excretory
granules
Organels
Some cells lack organelles ( RBCs)

15. Red blood cells
• Lack most of the organelles
– Nucleus (DNA)
• No cellular division and protein synthesis
– Mitochondria
– No ATP production in oxidative phosphorylation
• Glycolysis source of energy
– One glucose molecule  2ATP
15

16. Organelles
• Nucleus
– Largest organelle at the center of the cell
– Has nuclear membrane with nuclear envelop
– Controls the cell functions
• The genes
• Genes: molecules on the DNA that carry and express traits
• Each gene has its own triplet code word
– The functional unit of gene
Gene Gene I Gene II Gene III
code word with sequence CAG AGC GAC
Specific proteins (hormones,
enzymes,activitors, inhibitors)
Protein type I Protein type II Protein type III
16

17. DNA structure
Fig 5: DNA structure(
alpha double helix of two
polynucleotide strands).
17

18. Ribosomes and Endoplasmic reticulum
18
Free
Exocytosis
(active)
sER
 store Ca++(SR in muscle cells)
Steroids
Glycogen phosphatase
Glucokinase
Phosphoglucomutase
phospholipids
GA
 More in
secretary cells
(plasma B cells
and acinar cells )
Fig
6:
Ribosmomes
and
ER

19. Mitochondria and ATP production
19
Fig 7: Mitochondrion
38 ATP’s from one glucose
molecule but 2ATP used for
preparation steps
Nicotinamide
adenine
dinucleotide
(NAD):
NADH
is
the
reduced
form
of
NAD
and
carry
energy
2NADH
2

20. Lysosome …
20
Fig 8: Actions of lysosome
phagosome
Intracellular digestive
system: stomach of
the cell
Suicide
Acid hydrolic enzyme (pH<7)
cytosol pH =7.2

21. Secretory vessicels
• Similar structure with lysosomes
• Contain enzymes not used in the cell, released out
• Glandular cells have secretory vesicles
– Pancreatic gland
– Salivary gland
– Other endocrine gland
21

22. Peroxisomes ( from ER) and action of catalase
22
harmless
Harmless
Fig 9: Action of catalase and peroxidase
Fe losses O2
Oxidized
: Facilitate the formation of H2O2
Peroxisomes
 Replicated from ER
 Release catalase
 Shorter and smoother
Oxidation: 02 gaining and reduction loss of O2. iron reduced 02 this is b/se CO receive
oxygen Thus
CO : reducing agent as it facilitates Fe to loss O2
Fe: oxidizing agent as it facilities CO to gain 02 and oxidized
Oxidized substrate: reducing agent
Reduced substrate: oxidizing agent

23. Cell junctions and types
23
Sheet epithelial cells, BBB
Fig 10: Cells communication
provide strong mechanical
attachments between adjacent
cells.
Electrical signal conducted
1
2
3
4

24. Transport across the cell membrane
24

25. Membrane transport
 Passage of substances across the cell membrane
 Into the cell: influx and Out the cell: efflux
 The passage can be through:
 Lipidbilayer
 Proteins
 Cells differ in their permeability: Variation in :
– Composition and arrangement
25

26. Transport across the cell membrane
26
-Nutrients
-Ions and
Water are
through
-
With out proteins
 Gas
Lipid soluble substances
Alcohol
Protein
Fig 11: Transportation across the cell membrane

27. Types of membrane transport
• Passive transport
– No energy required
• Movement down concentration gradient
• The forces are concentration & electrical gradients
• Substances follow their concentration gradient
– Concentration gradient reduced /eliminated
– Filtration , simple or carrier mediated diffusion and osmosis
27

28. Types of the passive transport...
1 - Simple diffusion
– Through lipid bilayer or leaky channels- not gated ion channels
– Lipid soluble, gas and alcohol (via lipid bilayer)
• Vitamin A, D, E and K
– Lipid insoluble ( via water filled channels)
• Ions , water
– No interaction b/n channel and transported substance
28

29. Transport across the cell membrane
29
Fig 12: Types of Transport

30. Properties of channels
- Water field proteins
- Mostly, allow substances to move down (passive channels- leaky ion
channels)
- Dissipate potential difference
- Opened and closed by gate (gated channels)
- Active channels
- Prolonged activation desensitizes the channels
- Select influx and efflux substances
- Connected with receptors
- E.g ion channels
- Important for excitable cells
30

31. Gated Ion channels con’t
31
 Voltage gated ( charge difference sensors)
Ligand or Chemical gated (Ach, GABA, glutamate)
Light gated (photo sensitive channels)
Mechanical gated ( stretched sensitive channels)

32. Bases of selectivity
 Channels are specific and selective
 The selection is based on
 Size (size of Na+ channel: 0.3 x 0.5 nm)
 The bond nature of the proteins
The charge
 Hydration/unhydration of ions
 Na+ channel (-ve Q) allows unhydrated sodium to pass
 But hydrated potassium still pass through its channel
 The selectivity is less than the carriers
 Not have binding site
32
Unhydrated ion
Hydrated ion
ion
ion
H20

33. Factors affecting the diffusion rate: rate of transport
• Cell membrane thickness
• Molecular Size
• Temperature
• The gradient (electrical and concentration: opposite forces)
– Net influx, F = kpA(C0-Ci)
– The net efflux, F= kpA(Ci-C0)
• kp(Permeability constant)
• The lipid solubility
• Membrane surface area
• Permeability
33
1 2

34. Passive transport…
2- Facilitated diffusion
– It is carrier (permease ) mediated
– Solute binds to the carrier (conformational changes)
• Rotate, open
– The substance is released into the low concentration side
– Substances attached from high concentration region
34

35. Facilitated diffusion…
35
The unique feature of
facilitated diffusion
1. Specificity
2. Competition
3. Inhibition
4. Saturation
5. Transport maximum
Fig 13: Facilitated diffusion

36. Facilitated Diffusion…
– Differ from simple diffusion mainly
• Transport maximum(Vmax) achieved
– Diffusion rate elevated until transport maximum
– Proteins are saturated
– Diffusion rate constant after V max
36
Fig 14: Transport maximum(v max )
Rate of transportation increased as
the concentration of the substance
getting high

37. Passive transport: osmosis and osmotic pressure
3- Osmosis
– Net movement of water from
• The region of high water molecules to low water molecules
• Low solute to the high solute concentration
• Hypotonic to hypertonic solution
– Equalizes water concentration across the membrane
– This movement is there if there is
• Water and solute concentration difference
37

38. Solution tonicity
• Tonicity
 The osmotic activity of body fluid
 Ability of a solution affecting cell volume
 The solution:
 Isotonic, hypotonic and hypertonic against cytosol
 Affects the osmotic pressure of the solution
38

39. A cell in different solution
Solution concentration
compared with concentration
of intracellular fluid
What will be the cell volume if
you add different solution into
the ECF?
 isotonic solution
Hypertonic solution
Hypotonic solution
Fig 15: a cell in different solutions

40. Osmol, osmolarity, osmolality
• Osmol
– Number of osmotically active particles of solute in a solution
• Osmolarity: solute pr kg of solution and is the concentration of
the solution with the unit of mOsmol/L of solution
– The total osmolarity of the body is 280mOsm/L of solution
– And one milliossmole has an osmotic pressure of 19.3mmHg
• Osmolality: solute per kg of water
40

41. Atomic and molecular weight
Atomic weight of elements Molecular weight of compound
Table 1: atomic and molecular weight
41

42. Osmosis and osmotic pressure
• Osmotic pressure
– Force applied by solution to oppose the net movement of water
– Affected by osmole and the tonicity of solution :
• One mole of glucose= 1 osmole/L
• One mole of NaCl = 2 osmole/L
• One mole of HCl = 2 osmole/ L
• One mole of Na2SO4 = 3 osmole/L
– The more the osmotic pressure
• The less movement of water into other compartment
– Size of the molecule in the solution not affect osmotic pressure
• One mole of glucose (C6h12O6) ?
• One mole of NaCl?
42

43. Osmosis and osmotic pressure...
• Determination of osmotic pressure of a solution
– Osmolarity (mOsmol/L) = concentration x number of
dissociable particules
– E.g a 150 mmol/L (conc) solution of NaCl has an
osmolarity of 300 mOsm/L
– Then the osmotic pressure = 5,795mmHg
43

44. Relation between osmol and osmotic pressure
• A solution with 1 miliosmol/L opposes the net movement of water
by 19.3mmHg force
– The osmolarity of the body fluid is 280-300miliosmol/L
– Then the calculated body fluid osmotic pressure= 19.3 x 300 =
5790mmHg
– But the actual total body fluid osmotic pressure is 5500mmHg
(contributed by ions, proteins….)
– The reduction is due to some ions attract to each other like Na+
and Cl- in that their full osmotic effect is reduced
44

45. Molarity and osmotic pressure of a solution
• Calculate the osmolarity and the osmotic pressure of a solution of 0.9% NaCl
• Assume the membrane is impermeable to other solutes
– 0.9% NaCl solution means the solution contains 0.9gm of NaCl in 100ml of the solution
or 9gm/L
 Osmolarity = concentration x osmol
 (9gm/L)/(58.5 gm/mole)= 0.1538mole/L, then for two osmole = 2x
0.1538mole/L = 0.308 osmole/L
 Osmotic pressure
 1mosmle , the osmotic pressure required is 19.3 mmHg
 Then for 0.308 osmole/L = 308mosmole/L = 308 mosmole/L X 19.3 mmHg = 5,
944.4mmHg
45

46. Determination of fluid shift and osmolarities
of a solutions after an other solution infused
• Assume : 2L of hypertonic solution with 3.0% of NaCl infused
into ECF of a 70kg patient whose initial plasma osmolarity is
280mosmole/L. Then determine
– Osmolarity of body after infusion
– Intra and extracellular fluid volumes
46

47. Steep one: Determine the initial conditions before
solution given
47
Table 2: Initial condition of subject

48. • 3.0% Nacl solution means , solution contain 3mg of NaCl in 100ml
or 30gm/L
• Osmol/conc= 30gm/L/58.5gm/mole = 0.513mol/L x 2
=1.023mol/L
• For 2 L= 2x 1.023mol/L = 2.051mol/L = 2051mosmol/L
Thus the total ECF osmole = 3,920 + 2,051mosmo/L =
5,971mosmol/L
48
Steep two: determination of milliosmoles added

49. 49
Step 3: Determine the concentration in each L of solution
Table 3: Conditions after infusion before equilibrium

50.  Concentration= total miliosmoles in the body/ total volume
13,814/44 = 313.9mosml/L
 The fluid compartments will have the same concentration,
313.9mosml/L
 ICF volume = Total miliosmoles in ICF/ its concentration
= 7840/313.9 = 24.89L
ECF volume = total milimoles in ECF/ its concentration
= 5971/313.9 = 19.02L
50
Steep 4: determination of volume & concentration
after osmotic equilibrium is developed

51. The result (after infusion and equilibrium)
51
Table 4: conditions after equilibrium

52. Active Transport
• Transporter proteins (pumps) use energy
– Pump mediated and bulk transport
– Energy sources: ATP and ions
• Against concentration gradient.
• Gradient elevated
• Example Na+-K+ pump, Ca++ pump, movement of amino acids
into cell and movement of calcium into SR
52

53. Transporter proteins
Proteins
Cotransporter
Uniportor Symporter Antiporter/exchanger
Example Na+, Ca++, K+ ,
H+ channels
Na+-glucose or Na+-
amino acid
transporters ,Na+- K+
and 2Cl-
Na+-K+ (neurons), Na+-
Ca++ (heart cells), K+ -
H+ (kidney and
stomach) exchangers
53
Table 5: Transporter proteins

54. A) Ion driven
 Down hill ion movements uphill the solutes
 Indirect source of energy is ATP
B) ATP-driven: primary or direct
 ATP hydrolyzed by ATPase to drive uphill solute
Two types active transport
54

55. Mechanism of Na+- K+ pump and the functions
55
1. Regulate cell volume
2. Create membrane potential
(electrogenic effect): electrogenc
effect
3. Maintain ion diffusion gradient
4. Contribute for 20 active
transport
Fig 19: Sodium- potassium pump

56. 2) H+ -K+ pump on parietal cells apical membrane
56
Fig 20: Hydrogen- potassium pump

57. Secondary active transport
57
Na+
Secondary active
transport
Fig 21 : 20 active transport