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Introduction to Human Physiology
By
Yigizie Yeshaw(MSc)
University of GondarUniversity of Gondar
College of Medicine & Health SciencesCollege of Medicine & Health Sciences
Department of PhysiologyDepartment of Physiology
yigizieyeshaw29@gmail.comyigizieyeshaw29@gmail.com
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Objectives
At the end of this chapter the student will be able to:
1. Define what physiology mean
2. Explain homeostasis.
3. Discuss negative & positive feed back mechanism.
4. Discuss cell physiology.
5. Enumerate the cell organelles with their function.
6. . Body fluids
7. Describe PM components and transport across
8. Define membrane potential and its causes
9. Action potential
3. 3
What is Physiology?
Physiology is the study of the normal functioning of a
living organism and its component parts, including all its
chemical and physical processes
Fields of physiology
Ranges from simple viral physiology, bacterial physiology, cellular
physiology to the most complex human physiology
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4. Human physiology
Explain the specific characteristics and mechanisms of the
human body that make it a living being.
The fact that we remain alive is the result of complex
control systems.
Example
– Hunger makes us seek food, and
– fear makes us seek refuge.
– Sensations of cold make us look for warmth.
these special attributes allow us to exist under widely varying
conditions, which otherwise would make life impossible.03/19/17 4
5. An important part of physiology is understanding
how different parts of the body are controlled,
how they interact, and
how they adapt to changing conditions
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6. 1. William Harvey in 1628
Blood was pumped out of the heart through one set of vessels and
returned to the heart through another set.
2. Claud Bernard, in the 19th
C
Described that every cell in body is bathed with the fluid environment
called extracellular fluid(ECF).
He called ECF is the internal environment of the body.
3. Walter cannon-
Define homeostasis as maintenance of constant conditions in the ECF
Historical background
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7. Relationship b/n Physiology and other sciences
Physiology has a strong link with other disciplines
It is Highly related to
Anatomy
Biochemistry
Pathology
Pharmacology etc
Physiology as a quantitative science
All physiological parameters are expressed in numbers
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8. Levels of the Organization of the Human Body
chemical level cell tissue organ system organism
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9. 1. Cell
The basic structural and functional unit of an organism.
It is the smallest living unit of the human body
But play a big role in making our body function
properly.
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10. The entire body contains about 100,000,000,000,000 cells.
Each type of cell is specially adapted to perform one or
a few particular functions. e.g. RBC- transport oxygen
from the lungs to the tissues
Each cell has basic requirements to sustain it and
The body's organ systems are providing these many
cells with those basic needs (oxygen, food) and
remove waste products.
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11. There are many different types of cells in the body including:
Nerve cells
Blood cells
Epithelial cells and
Muscle cells
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12. 2. Tissue
When many identical cells are organized together it is called a tissue
There are four types of tissues in the body:
1. Epithelial tissue
2. Connective tissue
3. Muscle tissue
4. Nervous tissue
3. Organ
Organs are structures that are made of two or more different types of
tissues.
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13. 4. System
Consists of related organs that have a common function.
There are 11 organ systems in the body:
1. Respiratory System
2. Cardiovascular System
3. Digestive System
4. Urinary System
5. Reproductive System
6. The Skeletal System
7. Muscular System
8. The Integumentary System
9. Nervous System
10. Endocrine System
11. Lymphatic & Immune System
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14. 5. organism –it is the highest level of organization.
e.g human
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CVS GIT RS
Renal
System
Skeletal
System
Muscular
system
15. Homeostasis
Homeostasis is maintenance of nearly constant conditions in the
internal environment (ECF).
But this does not mean that its composition are absolutely
unchanging.
Both external and internal factors continuously threaten to
disrupt homeostasis.
Factor disrupting homeostasis:
External stimuli
heat, cold,
lack of 02,
pathogens & toxins
Internal stimuli
abnormalities in visceral organs03/19/17 15
16. When any factor starts to move the internal environment
away from optimal conditions,
the body systems initiate appropriate counter reactions to
minimize the change.
For example, Exposure to a cold/to warm environmental
temperature tends to decrease/ increase the body’s internal
temperature.
– Shivering in response to cold environment
– Sweating in response to high temperature
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17. 17
Essentially all organs of the body perform their functions to
maintain constant conditions in the ECF. For example
Respiratory system(RS)
The blood picks up oxygen in the alveoli, thus acquiring the
oxygen needed by the cells
Carbon dioxide is released from the blood into the lung alveoli
for exhalation
So RS help to maintain the normal concentration of respiratory
gases in blood.
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19. Gastrointestinal system
different dissolved nutrients are absorbed from the ingested food
into the extracellular fluid of the blood.
some waste products of metabolism are eliminated in the
feces
Renal system
Passage of the blood through the kidneys removes substances
that are not needed by the cells from the plasma.
The kidneys maintain constant ionic concentration
Musculoskeletal System
Provides motility for protection against adverse surroundings
Allow movement to obtain the foods required for nutrition
Hemopoiesis and Mineral storage
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20. Immune System
protect the body from pathogens
Integumentary System.
provide a boundary b/n the body’s internal environment and the
outside world.
cover, cushion, and protect the deeper tissues and organs of the
body
temperature regulation and excretion of wastes
Reproductive system
Have less role for homeostasis
help maintain homeostasis by generating new beings to take the
place of those that are dying.
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Regulatory Systems of Homeostasis
• The nervous
system and the
endocrine system
are the two
controlling bodies
of homeostasis
Effector cell
NTs
Receptor
Nerve Impulse
Hormone
Receptor
22. 22
Regulatory systems of homeostasis
1. The nervous regulatory mechanism
The nerves system is composed of three major components the
I. Sensory portion- The sensory receptor detects any change in
the body (BGC, BT, ABP, pain etc) and send impulse to the
CNS(brain, spinal cord).
II. Integrative portion -The CNS associate the information store
some, generate thought.
III. Motor portion - send appropriate response to the effecter
organs (muscle + glands).
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Regulatory systems of homeostasis…
2. The hormonal regulatory mechanism
Hormones are chemical messengers secreted by endocrine glands,
and transported in blood to the target organs.
Examples:
• PTH act on the kidney, bone, and intestine = [Ca2+]
• Aldosterone to the kidney [Na+]
An organism is said to be in homeostasis when its internal
environment contains an optimum amount of
1. Nutrients
2. Gases
3. Electrolytes
4. Water
5. Hormones
6. Enzymes and temperature.03/19/17
24. To stabilize the physiological factor being regulated,
homeostatic control systems must be able to detect and
resist change.
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25. Homeostatic control systems…
1. Feed-forward control
The term feed forward is used for responses made in
anticipation of a change.
• The regulatory processes established before the change is
developed.
Correction is by anticipation- Example
- HR and RR before actual exercise
- Digestive juice before food inter
into GIT
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26. • When meal is still in the GIT, there is an increase insulin
– that will promote the cellular uptake and storage
glucose after absorption.
– This anticipatory response helps limit the rise in
[BGC] after absorption.
• Used to adapt and rapid rate of response to the change.
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27. II. Feedback control
It refers to responses made after a change has been
detected;
– The regulatory processes established after the change is
developed.
• These feedback systems alter the function of organs by
increasing or decreasing their activities.
• There are two types of feed back mechanisms:
1.Negative feedback mechanism
2.Positive feedback mechanism
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28. 28
Negative Feedback Mechanism (NFM)
It works by producing an effect which opposes the previous
condition (the initiating stimulus) of the organ.
A negative feedback control system contains the following
elements:
1. A set point value, which is at the center of the normal range of
a variable and is treated by the control system as the target
value
2. Sensors that continuously monitor the controlled variable
3. A comparator (control center), which interprets input from
the sensors to determine when deviations from the set point
have occurred
• The comparator initiates a counter response
1. Effectors are the mechanisms that restore the set point to its
normal level
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30. Stimulus:
Produces
change
in variable
1
2
3
Change
detected
by receptor
Input:
Information
sent along
afferent
pathway to
5 Response of
effector feeds
back to influence
magnitude of
stimulus and
returns
variable to
homeostasis
Variable (in homeostasis)
Imbalance
Imbalance
Receptor (sensor)
Control
center 4 Output:
Information sent
along efferent
pathway to
Effector
Homeostatic Control Mechanisms
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31. Most homeostatic values of the body are controlled by NFM.
Example :
1. Control of Blood Glucose Level
2. Control of Body Temperature
3. Control of Calcium
4. Control of Arterial Blood Pressure etc.
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35. Human Thermoregulation
35
Brain senses change in blood temperature
if overheating, vessels dilate in the skin and sweating begins
if too cold, vasoconstriction in the skin and shivering begins
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36. 36
The Positive Feedback Mechanism (PFM)
It works by producing an effect which enhances or
repeats the same action like that of the starting stimulus.
“Positive” implies that when a deviation from a normal
value occurs, the response of the system is to make the
deviation even greater
Positive-feedback mechanisms are not homeostatic and
are rare in healthy individuals.
Examples of the PFM
1. Blood clotting
2. Labor during child birth
3. Generation and propagation of the action potential.
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PFM..
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3. Generation and propagation of the action potential.
Stimulated nerve fiber
opening of Na+ channels
entry of few Na+
stimulates the opening of more and more Na+ channels
40. Why do essentially all control systems of the body operate
by NFM rather than PFM?
– B/c positive feedback does not lead to stability but to instability
and often death. Example
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41. Heart of a healthy human being pumps about 5L of blood per minute.
If the person is suddenly bleed 2L blood
The amount of blood in the body is decreased to such a low level that
not enough blood is available for the heart to pump effectively.
As a result, the arterial pressure falls
coronary vessels blood flow diminishes
weakening of the heart, further diminished pumping, a further decrease
in coronary blood flow
still more weakness of the heart; the cycle repeats itself again and again
until death occurs.
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42. 42
Homeostatic values
1. Body fluid volume(TBW) = 42 L
ICF = 28L(2/3rd
of TBW)
ECF = 14L(1/3rd
of TBW)
Interstitial fluid = 11 L(3/4th
of ECF)
Plasma fluid = 3 L (1/4th
of ECF)
2. Osmolality = 300 mosm/L, (285 – 300 mosm/L)
3. Body T. = 36.5 – 37.4O
C
4. pH = 7.35 – 7.45
5. Blood Gases - PCO2 = 35 – 45 mm Hg
PO2 = 40 – 104 mm Hg
6. Electrolytes (ECF)
Ca2+
= 10 mg/dL or 5 meq/L
K+
= 4 meq/L
Na+
= 142 meq/L
Cl-
= 103 meq/L
HCO3
-
= 27 meq/L
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43. 43
Homeostatic values
7. Waste Products
Bilirubin = 0.5 mg/dl
Creatinine = 0.6 – 1.5 mg/dL
Blood urea nitrogen (BUN) = 8 – 25 mg/dL
Uric acid (s): Women = 2.3 – 6.6 mg/dL
Men = 3.6 – 8.5 mg/dL
8. Blood Glucose level (fasting): 70 – 110 mg/dL
9. Arterial Blood pressure (systemic circulation).
Systolic pressure = 120 mm Hg (90 – 140 mm Hg)
Diastolic pressure = 80 mm Hg (60 – 90 mm Hg)
Pulse pressure = 40 mm Hg
Mean BP = 96 mm Hg
Pulmonary AP = 25/10 mm Hg
Cardiac output = 5 L/min
Blood Flow = 5 L /min
10. RBC count = 4-6 millions/mm3
11. WBC count = 4000-11,000/mm3
12. Hb = 12-18 g/dl in F, 14-20 g/dl in M
13. Platelets = 150,000-450,00003/19/17
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Disturbances of homeostasis
When there is lose in homeostasis, the organism tries to
compensate it.
– If compensation succeeds, wellness happens
– If compensation fails, illness or diseases happens
• Deviations from normal ranges = PATHOLOGY
• Disease: a state of disrupted homeostasis.
– Hypo/ Hyperthermia ….. ↓or↑ Temperature
– Hypo/ Hypercapnea ….. ↓or↑ PCO2
– Acidosis/Alkalosis ….. ↓or↑ PH
– Hypoxia/ Hyperoxia …. ↓or↑ PO2
– Hypo/ Hypercalcemia …. ↓or↑ Ca 2+
– Hypo/ Hyperglycemia … ↓or↑ Glucose
45. 45
Structural levels of organization of human body
Muscle cells
Nerve cells
Cells: 4 types Epithelial cells
Cells in the connective tissues
Muscle tissue
Tissues 4 types Nerve tissue
Epithelial tissue
connective tissues
Organs: Example: Heart, lungs
Organ system: Example: Respiratory system, CVS
Organism: Human organism
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46. 46
Generalized cell
Components of cells
A typical cell has two parts: nucleus and cytoplasm.
The nucleus is separated from the cytoplasm by a nuclear
membrane and
The cytoplasm is separated from the surrounding fluid (ECF) by
the plasma membrane
The different substances that make up the cell are collectively
called protoplasm.
Protoplasm is composed mainly of five basic substances: water,
electrolytes, proteins, lipids, and carbohydrates.03/19/17
47. Cell Physiology
» Two types of cells:
A. cells without typical nucleus = prokaryotes
B. cells with nucleus = eukaryotes
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48. Comparision b/n Prokaryotic and Eukaryotic cells
Eukaryotes
1.Have nucleus
2. Larger (10-100 µ m)
3.Cytoskeleton present
4.Membrane-bound organelles
present
5.RNA synthesis in nucleus,
protein synthesis in the
cytoplasm
6. Multiple linear chromosomes
Prokaryotes
1.No nucleus
2.Smaller (1-10 µm)
3.No cytoskeleton
4.Generally no membrane-
bound organelles
5.RNA and protein
synthesis occur in
cytoplasm.
6.Small circular
chromosome
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49. 49
The plasma membrane
It is a sheet-like structure that surround (enclose) the cell,
It separates the cellular contents from the ECF.
Regulates the passage of substances in and out.
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50. 50
The nucleus
The nucleus is the control center for the cells.
It contains the genes, which are units of heredity.
Chemically each gene consists of highly compressed DNA in the
form of chromosomes
Genes control cellular activity by determining the type of
proteins,
enzymes, and
other substances that are made by the cell.
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51. 51
The nucleus (cont’d)
Nucleoli- site for Ribosomal RNA is synthesis.
The nuclear contents are surrounded by a double walled
nuclear membrane.
The pores present in this membrane allow fluids,
electrolytes, RNA, and other materials to move between
the nuclear and cytoplasmic comportments.
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52. the nucleus with DNA the double strand genetic code
that stores and transmits genetic material, and
coordinates protein synthesis in ribosomes
Undertakes its transcription phase of protein synthesis
in the nucleus.
Following transcription, the mRNA leaves the nucleus
and travels to the cell's ribosomes, where translation
occurs
transcription translation
DNA RNA Protein synthesis
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53. 53
Cellular organelles
• Embedded within the cytoplasm are organelles or inner
organs of the cell.
These include
– the ribosomes,
– endoplasmic reticulum (ER)
– Golgi apparatus,
– mitochondria,
– lysosomes, and
– the cytoskeletal system (microtubules and microfilaments).
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56. 56
Ribosomes:
Are the sites of protein synthesis in the cell
Found in two forms:
1. Attached to the wall of ER or
2. As free ribosomes. They are found in two forms
I. Scattered in the cytoplasm and
II. Clustered (aggregated) to form functional units
called polyribosomes
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Endoplasmic reticulum (ER)
It is an extensive membranous structure that connects various
parts of the inner cell.
ER is also connected with the nuclear membrane.
There are two types of ER:
– rough ER and
– smooth ER.
rER is the site of protein synthesis
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58. 58
Endoplasmic reticulum (ER)
• The sER is free of ribosome.
• Function of sER varies in different cells.
• The sarcoplasmic reticulum of skeletal and
cardiac muscle cells are forms of sER.
• In the liver, the sER is involved in glycogen
storage and drug metabolism.
• ER can synthesize a group of drug metabolizing
enzymes called microsomal system.
Function of sER:-
1. Glycogen storage
2. Calcium storage
3. Lipid biosynthesis
4. Drug metabolism (detoxify)
Endoplasmic reticulum (rER and sER)
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Golgi Complex
The Golgi complex communicate
with the ER and acts as a
receptacle/container for hormones
and others substances that the ER
produces.
It then modifies and packages
these substances ( proteins) into
secretary granules.
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Mitochondria-power house
The mitochondria are literally the
“power plants-factory” of the cell, b/c
many of the reactions that produce
energy take place in mitochondria.
Major site of
ATP production
Oxygen utilization
CO2
formation.
Contains enzymes of krebs cycle and
oxidative phosphoryiation03/19/17
62. Lysosomes
Lysosomes are vesicular organelles that form by breaking off from
the Golgi apparatus and then dispersing throughout the
cytoplasm.
Contains aggregates of enzymes.
Well developed in macrophages.
Are called suicide bags
The lysosomes provide an intracellular digestive system that
allows the cell to digest
– damaged cellular structures
– harmful substances such as bacteria.
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63. Lysosomes …cont’d
Membrane bound organelles that contain
hydrolases(Hydrolytic enzymes)
Hydrolytic enzymes;
lipases,
proteases,
glycosidases,
nucleases etc )
The membrane surrounding the lysosome prevents the enclosed
hydrolytic enzymes from coming in contact with other substances in
the cell and, therefore, prevents their digestive actions.
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64. Peroxisomes
Also called small bodies and they are spherical in shape
Are membrane bound organelles containing enzymes; oxidases and
catalases
– Surrounded by single membrane
Have protective role in that they secrete chemical that converts
harmful substances into harmless
E.g. Catalase is a type of oxidase produced by peroxisomes and
converts:
» H2O2 catalase H2O + O2
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65. Peroxisomes
Are similar physically to lysosomes, but they are different in two
ways:
They formed by self-replication (or perhaps by budding off
from the sER) rather than from the golgi apparatus
They contain oxidases rather than hydrolases
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66. Cell to Cell communication
Cell to cell communication very important for multicellular
organisms.
1. Endocrine signals
produced by endocrine cells
travel through the blood to reach all parts of the body.
1. Paracrine signals
target only cells in the surrounding area of the releasing
cell. E.g Neurotransmitters
1. Autocrine signals
Affect only cells that are of the same cell type as the
emitting cell. E.g. immune cells
1. Juxtacrine signals(Paracrine signals+Autocrine signals)
are capable of affecting either the emitting cell or cells
immediately adjacent03/19/17 66
68. Junctions between Cells
• Multicellular organisms
requires specific interaction
b/n cells to hold the cells
together and to
communicate in order to
coordinate activities.
• Five kinds of junctions
– Tight junctions
– Adherens junctions
– Gap junctions
– Desmosomes
– Hemidesmosome
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71. a. Tight junctions(occluding junctions)
Help plasma membranes of adjacent cells to fuse together,
forming an impermeable junction that encircles the cell.
They prevent molecules from passing through the
extracellular space between adjacent cells
So most materials must actually enter the cells (by
diffusion or active transport) in order to pass through the
tissue
For example, tight junctions b/n epithelial cells lining the
digestive tract keep digestive enzymes and
microorganisms in the intestine from leaking into the
bloodstream
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72. b. Gap Junctions(communicating junction)
It is a communicating junction b/n adjacent cells
At gap junctions the adjacent plasma membranes are very
close, and the cells are connected by hollow cylinders
called connexons.
Allow ions and small molecules to pass for intercellular
communication
Present in electrically excitable tissues, such as smooth
muscle and the heart, where ion passage from cell to cell
helps synchronize their electrical activity and contraction.
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72
73. c. Anchoring junctions
These junctions are most abundant in tissues that are
subject to constant mechanical stress such as skin and
heart
1. Adherens Junctions
Provide strong mechanical attachments between adjacent cells
Ties cells with other cells or EC matrix
They hold cardiac muscle cells tightly together as the heart
expands and contracts
They hold epithelial cells together
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74. 2.Desmosomes
Desmosomes are localized patches that hold two cells tightly
together
They are common in epithelia (e.g, the skin).
3. Hemidesmosomes
These are similar to desmosomes but attach epithelial cells to the
basal lamina ("basement membrane" instead of to each other
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75. Human Body fluid
The approximate composition of an average adult human per body
weight is that:
– Water = 60%
– Proteins = 18%
– Fats = 15%
– Minerals = 7%
What is Body Fluid(BF)?
The term BF refers to the body water + its dissolved substances
BF comprises an average of 60% of total body weight
The TBW in a 70kg adult man averages about 42 L, distributed
as: ICF and ECF
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76. 76
The fluid environment of the body
This 60% of human BF(42 L) is distributed in 2 compartments
1. Intracellular fluid compartment (ICF)
-Fluid inside the cell (28L) -which is 2/3rd
of TBW
2. Extracellular fluid compartment (ECF)
-fluid out side the cell(14 L) –which is 1/3 of TBW.
-2 Subdivisions:
I. Blood plasma (1/4th
of the ECF) =3.5L
II. Interstitial fluid (3/4th
of the ECF )=10.5L
III. transcellular fluid(1% to 3% of body weight)
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78. Transcellular fluid include
CSF,
aqueous and vitreous humor of the eye,
secretions of the digestive tract and associated organs
(saliva, bile, pancreatic juice),
renal tubular fluid and bladder urine,
synovial fluid, and sweat
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79. Extracellular fluid compartment (ECF)
• Contain ions and nutrients needed by the cells to
maintain life.
• This ECF is in constant motion throughout the body.
It is transported rapidly in the circulating blood and then
mixed between the blood and the tissue fluids by
diffusion through the capillary walls.
Thus, all cells live in essentially the same
environment(the ECF,milieu intérieur or internal
enviroment).
Cells are bathed with ECF.
This fluid contains an optimum amount of nutrients,
gasses, hormones, enzymes, water and electrolytes03/19/17 79
80. Cells are capable of living and performing their special
functions as long as the proper concentrations of
oxygen,
glucose,
different ions,
amino acids,
fatty substances and other constituents
are available in this internal environment(ECF).
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83. These two fluid compartments differ strikingly in terms of their
electrolyte composition
The blood plasma, interstitial fluid, and lymph are nearly
identical in composition, except for the higher protein
concentration in the plasma
But the fluid compartments solute concentrations (osmolarity)
are normally equal (no an osmotic difference between cells
cytoplasm/ICF and ECF)
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84. Disturbances of Water Balance
• Disturbances of body fluid volume may be
hypervolemia (excess fluid retention) or
hypovolemia (loss of fluid or dehydration)
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85. Disturbances of body fluid volume
– Hypervolemia may be caused due to:
1. Liver disease
2. kidney disease
3. Heart disease
4. Mismanagement of IV fluid
– Hypovolemia may be caused due to:
1. Excessive diarrhea
2. Excessive vomiting
3. Excessive sweating
4. Hemorrhage
5. Mismanagement of IV fluid
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86. Edema
• A typical (Abnormal) accumulation of fluid in the interstitial
space
– tissue swelling
• Causes:
– Caused by anything that increases flow of fluids out of the
bloodstream or hinders their return
1. Increase capillary hydrostatic pressure: as in obstruction of
venous system as in congestive heart failure
2. Decrease in the plasma colloid osmotic pressure: as in excess
loss of protein, in kidney diseases or decrease production, in
liver diseases or malnutrition
3. Obstruction of lymph vessel: accumulation of proteins in the
interstitial spaces
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88. 88
The plasma membrane
It composed of proteins, lipids and carbohydrates in
proportion of
Proteins- 55 %
Phospholipids 25 %
Lipids- 42 % Cholesterol 13 %
Neutral fats 4 %
Carbohydrate-3%
cholesterol determines rigidity of the membrane and
used to stabilizes the cell membrane
89. 89
Function of the plasma membrane
1. Separates cellular contents from the ECF
2. Regulates the passage of substances in and out.
It is semi-permeable allowing some subs to pass
through it excluding others. This creates unequal
distribution of ions on both sides of the membrane.
it allows oxygen and nutrients to enter the cell while
keeping toxins and waste products out
90. Function of the plasma membrane…
3. It provides receptors for NTs, hormones and
drugs.
4. It is a means of cell to cell contact.
5. Plays an important role in the generation and
transmission of electrical impulse in nerves &
muscle.
6. Involved in the regulation of cell growth and 90
91. 91
Components of cell membrane
A plasma membrane is a
fluid in its nature.
Lipids form the basic
structure of the membrane.
The lipid molecules are
arranged in two parallel
raws, forming a lipid
bilayer.
ECF ICF
1. Lipid
92. Cont,d
• The lipid bilayer portion of the
cell membrane is impermeable to
water and water soluble
substances such as
– ions,
– glucose,
– urea and others.
• On the other hand, fat soluble
substances such as
– O2,
– CO2,
– alcohol and drugs
can penetrate this portion of the
membrane.
92
94. Arranged as a Phospholipid bilayer
polar
hydrophilic
heads
nonpolar
hydrophobic
tails
polar
hydrophilic
heads
• Serves as a cellular barrier / border
H2Osugar
lipids
salt
waste
impermeable to polar molecules
95. Permeability to polar molecules?
Membrane becomes semi-permeable via protein
channels
– specific channels allow specific material across cell
membrane
inside cell
outside cell
sugaraaH2O
saltNH3
96. 96
• The lipid molecules (primarily
phospholipids) contain a
– polar phosphate heads, soluble in water
(hydrophilic) and
– a non-polar tails that does not mix with
water (hydrophobic).
• The physical orientation of the lipid
bilayer structures is that the
hydrophilic ends of the lipid
molecules line up facing the ICF and
ECF.
• The hydrophobic tails of the
molecules face each other in the
interior of the bilayer.
97. 97
2. Proteins (Membrane proteins)
A. Integral or intrinsic proteins
Exist as globular units running through the width of the cell
membrane;
Partly hydrophilic (polar and protruding to cell surface) and
partly hydrophobic (non-polar and embedded in the lipid
bilayer).
Protruding part may often carry CHO chains or lipids attached
to their tips like flags.
Tightly associated with membrane and
Account for about 70% of the membrane proteins.
98. Many of them provide structural channels through w/c
polar substances can diffuse in and out of the cell.
Trans membrane proteins serve as:
Channels through which ions pass
Carriers which actively transports material across the
bilayer e.g. glucose
Pumps which actively transport ions
Receptors for neurotransmitters and hormones
98
99. 99
B. Peripheral or extrinsic proteins:
Hydrophilic and readily dissociated from membrane.
Free, floating on the surface (stud the inside and the outside of the
membrane)
Account for about 30% of the membrane proteins.
Bind specific hormones and proteins on cell membrane.
Peripheral proteins that bind to the intracellular surface contribute
to the cytoskeleton.
102. 102
3. Carbohydrates(Membrane carbohydrates)
Attached on the outside surface of the membrane, binding with
protruded integral proteins(forming glyco-proteins)
and lipid(forming glyco-lipid )
Function
– It is the site of receptors for NTs, hormones and drugs.
– Cell to cell attachment
103. Transport through cell membrane
What needs to cross the PM?
Nutrients and wastes
Signaling molecules
Fluid
Certain ions
The PM is a very important structure which functions
to allow certain substances to enter or leave the cell
still excluding others to cross the membrane
103
104. Transport through cell membrane…
Such a membrane is referred to as "selective
permeable“ ("semipermeable")
It can "pump" other substance into or out of the
cell against the concentration gradient
Both the protein portion and the phospholipids
portion of the membrane are involved in the
membrane permeability.
104
105. Transport through the cell membrane…
I. Cells have two categories of transport for the movement of ions and
small solute molecules across the plasma membrane. These are
1. Passive transport
transport process that happens without the cell needing to
expend any energy. It includes
Simple diffusion
Facilitated diffusion
Osmosis
1. Active transport
transport processes require energy (ATP) from the cell's reserves to
"power" them. It includes
primary active transport
secondary active transport
105
106. Transport through the cell membrane
II. The movement of large molecules across cell membrane
takes place by vesicular transport
1. Endocytosis
2. Exocytosis
106
108. 108
1.Simple Diffusion
• Diffusion is passive movement of substances down their
concentration gradient.
Factors affecting the net rate of diffusion
– Lipid solubility of the subs
– Membrane permeability
– Concentration difference or Pressure difference
Membrane permeability is affected by
– Membrane Thickness
– No of ion channels per unit area
– Temperature: T = thermal motion of molecule
permeability
– MW (molecular weight)
109. 109
Simple Diffusion…
• Rate of diffusion is determined by the following factors
summarized in the formula shown below.
C.A. T.S
• Rate of diffusion = D
Where, C = Change of concentration
S = Solubility in lipid of the sub.
A = Surface area of the membrane
T = Temperature
D = Distance or membrane thickness
MW = Molecular wgt of substances
• Examples: Substances that are transported by simple diffusion are
CO2, O2, alcohol, lipid soluble drugs and ions through specific
channels.
MW
110. 110
2. Facilitated diffusion
Carrier mediated transport
Do not need energy
Transports substances down
their concentration gradient
Is more rapid than simple
diffusion.
Is carrier-mediated and
therefore exhibits specificity
and saturation
Examples: transport of glucose,
proteins. (Macromolecules)
Glucose
Carrier protein
Cell membrane
ECF
ICF
111. Facilitated diffusion…
Unlike simple diffusion the
rate of facilitated diffusion
increases as the
concentration gradient
increases until all of the
carrier sites are filled.
At this point, the rate of
diffusion can no longer
increase with increasing
particle concentration.
This is called saturation,
111
Fig. Effect of concentration of a substance on
rate of diffusion by simple diffusion and
facilitated diffusion.
This shows that facilitated diffusion
approaches a maximum rate called the Vmax.
112. 112
3. Osmosis
• It is the power of movement of
H2O from an area of higher
amount of water to an area of
lower amount of water through
the semi permeable membrane.
• The direction of movement of
water is governed by the amount
of osmoticaly active particles
(solutes).
• The pressure that opposes osmosis
of water is called osmotic
pressure
• H2O molecules can not traverse
the lipid bilayer simply.
– Instead they pass through specific
water channels called aquaporins:
113. 2 requirements for osmosis:
Must be difference in solute concentration on the
2 sides of the membrane.
Membrane must be impermeable to the solute.
• Osmotically active solutes:
– Solutes that cannot pass freely through the
membrane.
113
114. Tonicity
Tonicity is defined as the ability of a solution to change
the shape of a cell immersed in it due to changes in the
cell’s water volume.
A solution with the same concentration of non-penetrating
solutes( as those found in cells) are isotonic, i.e., “the
same tonicity.
Cells exposed to such solution retain their normal shape
and exhibit no net gain or loss of water.
Most IV solutions are isotonic (e.g., 0.9% saline or 5%
glucose).
114
115. Direction of osmosis is determined by comparing
total solute concentrations.
A cell is
Hypertonic – if it has more solute, less water than
surrounding solution cell swelling
Hypotonic - if it has less solute, more water than
surrounding solution cell shrinking
Isotonic - equal solute, equal water to surrounding
solution
no change on cell volume
Movement of water out of the cell is exactly115
116. 116
Active transport
Substances are transported against concentration gradient, up hill
direction.
Consumes energy in the form of ATP
Used for the transport of Na+
, K+
, Ca2+
, Fe2+
, H+
, Cl-
1. Primary active transport
- Carrier protein in involved
- Consumes energy from ATP
Common examples
1. Na+ - K+ ATPase
2. Ca2+ ATPase(In the sarcoplasmic reticulum (SR).
3. H+
, k+
-ATPase(proton pump)
In gastric parietal cells transports H+
into the lumen of the
stomach against its electrochemical gradient.
It is inhibited by Omeprazole.
117. 117
Active transport: Na+ - K+ ATPase
Na-K-Pump
Na+ - K+ pump is a carrier protein that is
made up of two subunits. It has 3 binding
sites for Na+ inside and 2 binding sites for
K+ on the outside
It pumps 3Na+
outward and 2K+
inward
It maintains electropositive outside and
electro negation, inside.
Both Na and k are transported against their
electrochemical gradients.
It has ATPase activity inside.
ATP = ADP + ---P + energy.
Energy brings conformational change of
the pump so that Na+ pumped outward and
K+ inward.
119. 119
2. Secondary active transport
Carrier protein is
involved
Consumes energy
The movement of a molecule down its concentration gradient(
usually Na+) provides energy for the "uphill" transport of the
other solute(s). i.e. metabolic energy is not directly used but
indirectly from the Na gradient .
120. Binding of more than one molecule in one
direction – symport (cotransport).
e.g. -Na+ glucose cotransport in small intestine
- Na-K-2Cl- cotransport in the kidney.
If the solutes move in opposite directions across
the cell membranes, it is called countertransport,
exchange, or antiport.
• Examples are Na+
/H+
exchange and Na+
/Ca2+
exchange systems
120
121. Depending on the number of substances that carriers
transport, carrier proteins may be referred to as (Fig7a):
Uniport carriers: Carry single substance to one
direction
Antiport carriers: Carry two substances in opposite
directions, facilitating exchange of substances
Symport carriers: Carry two substances into the same direction
121
123. Vesicular
transport For transport of macromolecules. Two types
1.Endocytosis:-
cells internalize extracelluar material
Engulfing of materials by invaginating the outer part of a
cell membrane until it buds off within the cytoplasm
a.Phagocytosis: cell eating
Is the process by which bacteria, dead tissue, or other material are
engulfed by cells.
substance is a solid
Phagocytic cell(macrophages)
Are almost =to engulfed sub.
123
124. 124
b. Pinocytosis- cell drinking :
Is a similar process like phagocytosis but
the vesicles are much smaller in size
the substances ingested are in solution.
Invagination occurs into cell and pinches off to form
boundary of an intracellular vesicle, vacuole or
tubule.
129. Tissues which are capable of generation and
transmission of electrochemical impulses
along the membrane
E.g.- nerve and muscle
129
Excitable Tissues
130. • Neurons are functional & structural units of
the nervous system.
• Specialized to conduct information from one
part of the body to another
130
131. 131
Neurons
A neuron has 3 distinct parts. These
are:
Cell body , Dendrites and Axon
1. Dendrites
Are thin, branched processes whose
main function is to receive incoming
signals.
Convey info towards the soma through
the use of graded potentials.
132. 132
2.Soma( cell body)
Contains a very active & developed
rough endoplasmic reticulum
which is responsible for the
synthesis of NTs.
– The neuronal RER is referred
to as the Nissl body.
Acts as a receptive service
for interaction with other
neurons.
133. 133
3. Axons:
Convey info away from soma
Originates from axon hillock
( special region of soma)
Transmit APs from the soma
toward the end of the axon where
they cause NT release.
Often branch sparsely which end
in a synaptic knob, which contains
synaptic vesicles(membranous bags
of NTs).
Neuronal Processes…cont’d
134. 134
The tips of most axon terminals swell into synaptic
end bulbs.
These bulb-shaped structures contain synaptic
vesicles, tiny sacs that store chemicals called NTs .
The NT molecules released from synaptic vesicles are
the means of communication at a synapse.
135. 135
Membrane potential
All cells have a voltage difference across their
plasma membrane. This is called membrane
potential.
Changes in membrane potential are due to
changes in ion movement across the membrane.
The membrane potential (VM) at rest is called resting
membrane potential (RMP).
At rest, there are electropositivity out and
136. An average value for the resting membrane
potential of neurons is -70 mV
That is, the potential inside the fiber is 70mv more
negative than the potential in the ECF on the outside
of the fiber.
136
137. 137
What are the causes of the RMP?
1. An outward diffusion of K+
through K+
leak channels. The
ECF is very high in Na+
while the ICF is very high in K+
. As a
result, K+
is constantly leaking out of the cell.
2. The Na+
/K+
pump is constantly pumping 3 Na+
ions out and 2
K+
ions in for every ATP used. Thus more positive charge is
leaving than entering.
3. There are protein anions (i.e., negatively charged proteins)
within the ICF that cannot travel through the PM.
138. Ion channels
Are integral proteins that span the membrane and,
when open, permit the passage of certain ions.
May be
open (leak channels)
closed(gated channels)
When the channel is open, the ion(s) for which it
is selective can flow through.
When the channel is closed, ions cannot flow
through.
Opening and closing of channels are controlled by
gates 138
139. Four kinds of gated channels
1. Voltage-gated channels
-Are opened or closed by changes in membrane
potential.
2. Chemically gated channels
-Are opened or closed by hormones, second
messengers, or neurotransmitters.
3. Mechanically gated channels- respond to stretching
or other mechanical deformation
4. Thermally gated channels-respond to local changes
139
140. 140
Basic Electrophysiological Terms I
Stimulus : any change in the environment (internal or external
environmental condition of the cell).
Excitable cells: cells that generate action potential during
excitation-nerve and muscle cells.
Excitability: the ability to respond to a stimulus and convert it
into an action potential.
Threshold stimulus:
Any stimulus strong enough to initiate an action
potential (nerve impulse).
At threshold potential, net inward current becomes
larger than net outward current
141. Depolarization:
- the membrane potential becomes less negative
than the resting potential (-70 mV) (due to the
rapid opening of Na+ channel)
Repolarization:
- when the membrane returns to RMP after
depolarization (due to the slower opening of
K+channels and the closing of Na+ channels).
Hyperpolarization:
- membrane potential become more negative than
the resting potential (due to the out flow of K+
may be so great)
- Undershoot, or hyperpolarizing after potential 141
142. • There are two basic forms of electrical
signals:
1.Graded potentials
Graded potentials in neurons are depolarization's or
hyperpolarization's that occur in the dendrites and cell body or,,
near the axon terminals(less frequently).
If stimulus is not strong enough to depolarize the cell to
threshold at the trigger zone, and the graded potential dies out
without triggering an action potential
stronger initial stimulus that initiates a stronger depolarization142
143. 143
2. Action Potentials
An immediate change of the RMP
in to depolarization that is
followed by re-establishment of
the RMP (re polarization) is called
action potential (nerve impulse).
Action potential is a rapid,
conductive, and reversible
change of the membrane potential
after the cell is stimulated.
144. AP is a brief, rapid, & large changes in membrane
potential that conveys information within the
nervous system and in all types of muscle.
Action potential occurs only if the change in membrane
potential at the axon hillock is above threshold.
Unlike graded potentials, Aps are conducted, or propagated,
throughout the entire membrane in none decremental fashion
AP has 3 phases
1.Resting phase
2.Depolarization
3.Repolarization
144
145. 145
Action Potentials1. Resting potential: all voltage-
gated channels closed
2. When the change in membrane
potential reaches threshold level
Voltage-gated Na channels open
(Na+ activation gate opens) and
Na influx will occur( b/c Na
conc. outside is more than the
inside) causes
depolarization(This is the rising
phase of an AP)
3. When it reaches +35, Na
channels closes/
inactivated(Na+ inactivation
gate closes)
4. Then Voltage-gated K channels
146. 5. On return to resting potential, Na+ activation gate
closes and inactivation gate opens, resetting
channel to respond to another depolarizing
triggering event
6. Further outward movement of K+ through still-
open K+ channel briefly hyperpolarizes
membrane, which generates after
hyperpolarization.
7. K+ activation gate closes, and membrane returns
to resting potential.
K+
channels are slow to open and slow to close. This
causes hyperpolarization
146
147. But ionic distribution has become unequal
Na/K pump restores Na and K conc. slowly
– By pumping 3 Na ions outward and 2 K ions inward
147
151. 151
Voltage-Gated K+
Channels
• One gate
• Voltage-dependent (sensitive to
depolarization)
• Time-dependent
– Opens more slowly than Na
channels
• Slow closing results in
hyperpolarization
152. 152
Refractory Periods
Two types refractory period
1. Absolute refractory period( ARP)
The period during which a second action potential cannot be
elicited, even with a strong stimulus, is called the ARP
A new AP cannot occur in an excitable fiber as long as the
membrane is still depolarized from the preceding AP.
- A Na+
channel cannot be involved in another AP until the
inactivation gate has been reset.
153. ARP…
The reason for this restriction is
that after the AP is initiated, the
sodium channels become
inactivated and no amount of
excitatory signal applied to these
channels at this point will open
the inactivation gates.
– Because of the closure of
inactivation gate
outside
inside
153
154. 2.Relative refractory period
Follows ARP
VG K+
channels are open.
During this period nerve membrane
can be excited by supra threshold
stimuli
At the end of repolarization phase
inactivation gate opens and
activation gate closes
Some Na* channels that have not
quite returned to their resting
position can be opened by stronger
stimulus(Some Na channels still
inactivated will be opened with
greater stimulus.
-90
+35
outside
inside
154
155. Action potential is an ALL OR NONE EVENT (It happens
completely or it does not occur at all).
The AP fails to occur if the stimulus is sub threshold in
magnitude (it does not occur at all), OR
it occurs with constant amplitude regardless of the strength of
the stimulus if the stimulus is at or above threshold
intensity(It happens completely).
Once threshold intensity is reached, a full-fledged
action potential is produced .Further increases in the
intensity of a stimulus produce no increment or other
change in the action potential
155
156. Action potential vs Graded
potentialAction Potential
1. Amplitude is independent
of the initiating event.
2. Action potential can not be
summated
3. Has refractory period
4. Not affected by distance
5. Is depolarization with an
overshoot
6. Initiated by membrane
depolarization.
Graded potential
1. Amplitude varies with
condition of the initiating
event
2. Graded responses can be
summated
3. Has no refractory period
4. Is conducted decrementally,
amplitude decreases with
distance
5. Can be depolarization or
repolarization
6. Initiated by NTs, drugs,
hormones or spontaneously.
157. 157
Conduction of Action Potential
• If an AP is generated at the axon hillock, it will
travel all the way down to the synaptic knob.
• The manner in which it travels depends on whether
the neuron is myelinated or unmyelinated.
Unmyelinated neurons undergo the Sweeping
/continuous conduction/ of an AP whereas
Myelinated neurons undergo jumping /saltatory
conduction/ of an AP.
158. 158
1. Continuous (Sweeping) Conduction
• Occurs in
unmyelinated axons.
• The whole length of
the membrane is
depolarized (AP
occurs on whole length
of the axon membrane)
• Velocity of conduction
is slow
• Consumes large
amount of energy
159. 159
2. Saltatory (Jumping) Conduction
Occurs in myelinated axons.
AP occurs at the axon of nodes
of Ranvier.
Velocity of conduction is faster
(50 times faster than the fastest
unmyelinated fibers).
Consumes few amount of energy
(Economizes ATP)
161. 161
Factors Affecting Rates of AP Conduction
1. presence or absence of myelination
Myelinated axons faster rate of AP conduction than
unmyelinated axons
2. Diameter of fiber (size of nerve fiber)
An axon with a large diameter conduct an AP faster than
axon with a small diameter .
3. Age
Slower in babies and elderly
4. Temperature
When warmed, nerve fibers conduct impulse at highest speed;
when cooled at lower speed.
162. 162
Synapses
- The junction between two cells in which one must be a neuron.
- The region where there is a transfer of message from a neuron
to the next.
There are 3 types of synapses
1. Neuroneuronal junction
-the junction b/n two neuron Presynaptic and postsynaptic neuron
2. Neuromuscular junction
- the junction between neuron & muscle.
3. Neuroglandualr junction
-the junction b/n neuron & gland
163. 163
There are 3 types of neuroneuronal junctions
1. Axo-dendritic junctions
2. Axo-somatic junctions
3 Axo-axonic junctions
164. 164
Synaptic Transmission
Two types of synapses:
– Electrical synapses and
– Chemical synapses
1.Electrical synapses
Allow current to flow from one excitable cell to the next
via gap junctions(b/n the pre- and postsynaptic
neurons)
These gap junctions allow the transmission of the
depolarization wave directly from the pre- to the
postsynaptic membrane
Gap junctions are more numerous in smooth muscle and
166. 166
2. Chemical Synapses
More common than electrical synapse
One neuron will transmit impulse to
another neuron or
muscle or by releasing chemicals(NTs)
gland cell
Acts slower than electrical synapses
b/c the NT must diffuse across the synaptic cleft to
bind the receptor.
167. 167
Components of AxoSomatic synapse
1. Presynaptic terminal
contains neurotransmitter
(NT)
1. Synaptic cleft
contains ECF and Enzymes
1. Postsynaptic neuron
contains receptor for the
action of NT
168. 168
Mechanism of Chemical Synaptic Transmission
• An AP reaches the presynaptic axon terminal of the
presynaptic cell and causes V-gated Ca2+
channels to open.
• Ca2+
rushes in, binds to regulatory proteins & initiates NT
release by exocytosis.
• NTs diffuse across the synaptic cleft and then bind to specific
receptors on the postsynaptic membrane and initiate
postsynaptic potentials.
• NT-Receptor interaction results in either EPSP or IPSP.
169. 169
Mechanism of Chemical Synaptic Transmission…cont’d
• When the NT-R combination
triggers the opening of ligand
gated Na-channels, this leads to
membrane depolarization,
EPSP.
e.g. Ach on Nicotinic receptor
• When the NT-R combination
triggers the opening of ligand
gated K or Cl-channels, this
leads to membrane
hyperpolarization, IPSP.
e.g. GABA on GABAb receptor
170. 170
Excitatory Vs Inhibitory
Synapses
• Excitatory
- more likely to have action potential of postsynaptic cell
- depolarization
• Inhibitory
• Neurotransmitter binds to receptor, channels for either K or Cl
open
hyperpolarizes the cell (less likely to have action potential)
• If K channels open
– K moves out -IPSP
• If Cl channels open, either
– Cl moves in -IPSP
172. 172
Properties of synaptic transmission
Unidirectional conduction
Synaptic delay (0.5 -1.0m/s)
o The time required for the multiple steps in chemical
neurotransmission to occur.
Fatigue
- Decrease in response of postsynaptic neurons after
repetitive stimulation by the presynaptic neurons
possibly resulting from Depletion of NT stores from
the presynaptic terminal.
Synaptic potentiation (facilitation)
- Increase in postsynaptic responses caused by previous post
synaptic stimulation
The term physiology literally means knowledge of nature.
Aristotle (384 322 B.C.E.) used the word in this broad sense to describe the functioning of all living organisms, not just of the human body.
1. William Harvey in 1628
An English physician and anatomist
blood was pumped out of the heart (the central pump) continuously through one set of vessels and returned to the heart through another set, i.e. blood flows in a completely closed circulation.
Harvey could not see the microcirculation but he proposed its existence to complete the circuit from arteries to veins
Physiology started as an experimental science at this time .
2.Claud Bernard,
a French physiologist in the 19th C. described that every cell in body is bathed with the fluid environment called ECF.
ECF contains all the needed substances for cells.
He called ECF is the internal environment of the body.
3. Walter cannon- another great physiologist of 19th century termed the maintenance of constant conditions in the ECF as homeostasis.
100 trillion(100,000,000,000,000) cells.
Cells are the smallest living units within our body, but play a big role in making our body function properly. Many
cells never have a large increase in size after they are first formed from a parental cell. Typical stem cells reproduce,
double in size, then reproduce again. Most Cytosolic contents such as the endomembrane system and the cytoplasm
easily scale to larger sizes in larger cells. If a cell becomes too large, the normal cellular amount of DNA may not be
adequate to keep the cell supplied with RNA. Large cells often replicate their chromosomes to an abnormally high
amount or become multinucleated. Large cells that are primarily for nutrient storage can have a smooth surface
membrane, but metabolically active large cells often have some sort of folding of the cell surface membrane in order
to increase the surface area available for transport functions.
200 different types of cells
RBC= 25 trillion cells
There are about 200 different kinds of specialized cells in the human body.
There are many different types of cells in the body including:
Nerve cells-function to process and transmit information
Blood cells
Epithelial cells- lines both the outside (skin) and the inside cavities and function as secretion, absorption, protection, trans cellular transport
Muscle cells
These substances include different end products of cellular
metabolism, such as urea and uric acid; they also
include excesses of ions and water from the food that
might have accumulated in the extracellular fluid.
The immune system provides a
mechanism for the body to (1) distinguish its own cells
from foreign cells and substances and (2) destroy the
invader by phagocytosis or by producing sensitized lymphocytes
or specialized proteins (e.g., antibodies) that
either destroy or neutralize the invader.
Read page 7 0f gytun new edition
1. Feed-forward control
Some activities needed be rapid that no enough time for the brain to bring change after actual change occurred.
The brain anticipates the change that will be developed.
Help for adaptation of the organ where correction will be occurred.
When meal is still in the GIT, there is an increase insulin
that will promote the cellular uptake and storage of ingested nutrients after they have been absorbed from the digestive tract.
This anticipatory response helps limit the rise in blood glucose concentration after absorption.
Used to adapt and rapid rate of response to the change.
II. Feedback control
The body organs receive information (feedback) about the extent of their activities through the regulatory mechanisms (NS or ES).
Positive Feedback Can Sometimes Be Useful.
In some instances, the body uses positive feedback to its advantage. Blood clotting is an example of a valuable use of positive feedback. When a blood vessel is ruptured and a clot begins to form, multiple enzymes called clotting factors are activated within the clot. Some of these enzymes act on other unactivated enzymes of the immediately adjacent blood, thus causing more blood clotting. This process continues until the hole in the vessel is plugged and bleeding no longer occurs. On occasion, this mechanism can get out of hand and cause formation of unwanted clots. In fact, this is what initiates most acute heart attacks, which can be caused by a clot beginning on the inside surface of an atherosclerotic plaque in a coronary artery and then growing until the artery is blocked. Childbirth is another instance in which positive feedback is valuable. When uterine contractions become strong enough for the baby’s head to begin pushing through the cervix, stretching of the cervix sends signals through the uterine muscle back to the body of the uterus, causing even more powerful contractions. Thus the uterine contractions stretch the cervix and the cervical stretch causes stronger contractions. When this process becomes powerful enough, the baby is born. If it is not powerful enough, the contractions usually die out and a few days pass before they begin again.
Another important use of positive feedback is for the generation of nerve signals. That is, stimulation of the membrane of a nerve fiber causes slight leakage of sodium ions through sodium channels in the nerve membrane to the fiber’s interior. The sodium ions entering the fiber then change the membrane potential, which in turn causes more opening of channels, more change of potential, still more opening of channels, and so forth.
The Cell theoryIs the idea that all organisms are composed of cells.
In its modern form, the cell theory includes four principles:
1. All organisms are composed of one or more cells
2. Cells are the smallest living things
3. Cells arise only by division of a previously existing cell
Cells are constructed of the same basic elements and share the same basic materials and biosynthetic machinery
but differ by shapes and molecular structures
DNA and RNA are made up of nucleotides
Nucleotides are composed of nitrogen containing bases purine (A, G) and pyrimidin (C, T) as well as deoxyribose sugar conjugated by phosphate.
In RNA, the pyrimidin base T is replaced by U and the 5-carbon sugar is ribose.
In summary, the flow of genetic information in the cell is: DNA → RNA induce to facilitate protein transcription in nucleus →complex moves out of nucleus → protein translation in ribosomes.
Free ribosoms-Site at which amino acids are assembled into proteins. Site at which proteins to be used intracellular are assembled
Bound ribosoms-Site at which proteins to be secreted from cell are assembled. Cell movements. Also used to provide structural support at cell junctions
The function of rER is to segregate/isolate proteins that are being exported from the cell.
ATP
It is energy rich compound required for various cellular activities
Juxtacrine signals
are transmitted along cell membranes via protein or lipid components integral to the membrane and
Adherens Junctions
They seem to be responsible for contact inhibition
ECF is transported rapidly in the circulating blood and then mixed between the blood and the tissue fluids by diffusion through the capillary walls. Thus, all cells live in essentially the same environment(the ECF). For this reason, the ECF is also called the internal environment of the body(milieu intérieur).
Cholesterol has a rigid structure that stabilizes the cell membrane and reduces the natural mobility of the complex lipids in the plane of the membrane.
Proteins. After water, the most abundant substances
in most cells are proteins, which normally constitute 10
to 20 percent of the cell mass. These proteins can be
divided into two types: structural proteins and functional
proteins.
Peripheral proteins that are present only on one side of the membrane, serve primarily as enzymes ??????
CHO-antigenic activity in ABO blood groups (immune reaction ,antigenical importance) ?????
Factors affecting the net rate of diffusion
Electrical potential difference of ions ???
Carriers are saturable(Flux increases with extra-cellular concentration only up to a certain point )
Facilitated diffusion- Is carrier-mediated and therefore exhibits sterospecificity, saturation, and competition.
Osmolarity versus Osmolality The terms osmolarity and osmolality are frequently confused and incorrectly interchanged. Osmolarity refers to the osmotic pressure generated by the dissolved solute molecules in 1 L of solvent, whereas osmolality is the number of molecules dissolved in 1 kg of solvent. For dilute solutions, the difference between osmolarity and osmolality is insignificant. Measurements of osmolarity are dependent on temperature because the volume of solvent varies with temperature (i.e., the volume is larger at higher temperatures). In contrast, osmolality, which is based on the mass of the solvent, is independent of temperature.
Osmosis: is the power of a solution to dray the solvent through a semi-permeable membrane.
Osmotic pressure: is the pressure needed to prevent the mov’t of solvent across a semi-permeable membrane into a solution.
Osmoles: the ability of solutes to cause osmosis and osmotic pressure. Measured in ‘osmoles’. An osmole = the gram substance of the molecule dividing by the number of freely moving particles on solution e.g. NaCl (58.5g0/2 = 29.23g
Osmolarity: is the concentration of osmoticaly active particles per liter of solution (Osmoles/l). One osmole of a solute added to one liter of solvent.
Osmolality: is the conc. Of osmotically active particles per Kg of solution (Osmoles/Kg). One osmole of a solute and one Kg of solvent are added together.
Tonicity is the osmolality of a solution relative to osmolality of plasma
It is the osmolality of a solution relative to osmolality of plasma.
An Isotonic solution: has the same osmolality as plasma
If a cell is placed in a solution of impermeant solutes having an osmolarity of 282 mOsm/L, the cells will neither shrink nor swell because the water concentration in the intracellular and extracellular fluids is equal and the solutes cannot enter or leave the cell Such a solution is said to be isotonic solution
Isotonic solutions include a 0.9 per cent solution of sodium chloride (NSS);which is given for hypotension or a 5 per cent glucose solution which will given for dehydration and 1.8% urea
A Hypertonic solution: has a higher osmolality than plasma.
If a cell is placed in a solution having concentration >282 mOsm/L of impermeant solutes, water will flow out of the cell into the extracellular fluid, concentrating the intracellular fluid and diluting the extracellular fluid while the cell shrinks
Such a solution is called hypertonic solution
Sodium chloride solutions of greater than 0.9 per cent are hypertonic
E.g. 9% NaCl and 8% glucose
A Hypotonic solution: has a lower osmolality than plasma.
If a cell is placed into a solution with <282 mOsm/L impermeant solutes→ diffusion of water into the cell → swelling of the cell, diluting the intracellular fluid while also concentrating the extracellular fluid until both solutions have about the same osmolarity. Such a solution is called hypotonic solution
e.g., Solutions of sodium chloride with a concentration of less than 0.9 per cent are hypotonic and cause cells to swell (E.g. 0.6% NaCl, 3% glucose)
Substances are transported against concentration, electrochemical gradienT,up hill direction.
Calcium pumps, Ca2+-ATPases, are found in the plasma membrane, in the membrane of the endoplasmic reticulum, and, in muscle cells, in the sarcoplasmic reticulum membrane. They are also P-type ATPases. They pump calcium ions from the cytosol of the cell either into the extracellular space or into the lumen of these organelles. The organelles store calcium and, as a result, help maintain a low cytosolic concentration of this ion
The H+/K+-ATPase is another example of a P-type ATPase. It is present in the luminal membrane of the parietal cells in oxyntic (acid-secreting) glands of the stomach. By pumping protons into the lumen of the stomach in exchange for potassium ions, this pump maintains the low pH in the stomach that is necessary for proper digestion. It is also found in the colon and in the collecting ducts of the kidney. Its role in the kidney is to secrete H+ ions into the urine, when blood pH falls, and to reabsorb K+ ions
Proton pumps, H+-ATPases, are found in the membranes of the lysosomes and the Golgi apparatus. They pump protons from the cytosol into these organelles, keeping the inside of the organelles more acidic (at a lower pH) than the rest of the cell. They are also found in PM of bone and kidney cells. The secretion of protons by the bone cells (osteoclasts) helps to solubilize the bone mineral and creates an acidic environment for bone breakdown by enzymes. The proton pump in the kidney is present in the same cells (intercalated) as the H+/K+-ATPase and helps to secrete H+ ions into the urine when blood pH falls.
All co-transports have Na+ as one of the transported solutes; exception is yeast
All co-transports have Na+ as one of the transported solutes
The most important examples of antiporters are the Na+/H+ exchange and Na+/Ca2+ exchange systems, found mainly in the plasma membrane of many cells. The first uses the sodium gradient to remove protons from the cell, controlling the intracellular pH and counterbalancing the production of protons in metabolic reactions. It is an electroneutral system because there is no net movement of charge. One Na+ enters the cell for each H+ that leaves. The second antiporter removes calcium from the cell and, together with the different calcium pumps, helps maintain a low cytosolic calcium concentration. It is an electrogenic system because there is a net movement of charge. Three Na+ enter the cell and one Ca2+ leaves during each cycle.
Vesicular Transport
• Vesicles or other bodies in the cytoplasm move macromolecules or large particles across the plasma membrane.
Types of vesicular transport include:
1. Exocytosis, which describes the process of vesicles fusing with the plasma membrane and releasing their
contents to the outside of the cell. This process is common when a cell produces substances for export.
2. Endocytosis, which describes the capture of a substance outside the cell when the plasma membrane merges to
engulf it. The substance subsequently enters the cytoplasm enclosed in a vesicle.
There are three kinds of endocytosis:
• Phagocytosis or cellular eating, occurs when the dissolved materials enter the cell. The plasma membrane
engulfs the solid material, forming a phagocytic vesicle.
• Pinocytosis or cellular drinking occurs when the plasma membrane folds inward to form a channel allowing
dissolved substances to enter the cell. When the channel is closed, the liquid is encircled within a pinocytic
vesicle.
• Receptor-mediated endocytosis occurs when specific molecules in the fluid surrounding the cell bind to
specialized receptors in the plasma membrane. As in pinocytosis, the plasma membrane folds inward and the
formation of a vesicle follows.
Note: Certain hormones are able to target specific cells by receptor-mediated endocytosis.
b. Pinocytosis- cell drinking :
e.g. absorption of undigested protein in gut of newborns.
Electrical potentials exist across the membranes of virtually all cells of the body. In addition, some cells, such as nerve and muscle cells, are capable of generating rapidly changing electrochemical impulses at their membranes, and these impulses are used to transmit signals along the nerve or muscle
membranes.
Cell’s ability to fire an action potential is due to the cell’s ability to maintain the cellular resting potential at approximately –70 mV.???????
Selectivity is based on the size of the channel and the distribution of charges that line it.For example, a small channel lined with negatively charged groups will beselective for small cations and exclude large solutes and anions. Conversely,a small channel lined with positively charged groups will be selective for small anions and exclude large solutes and cations.• 2. Ion channels may be open or closed. When the channel is open, the ion(s) for which it is selective can flow through. When the channel is closed, ions cannot flow through.
There are four kinds of gated channels, depending on the factor that causes the change in channel conformation:
voltage-gated channels open or close in response to changes in membrane potential;
(2) chemically gated channels change conformation in response to binding of a specific extracellular chemical messenger to a surface membrane receptor;
(3) mechanically gated channels respond to stretching or other mechanical deformation; and
(4) thermally gated channels respond to local changes in temperature (heat or cold).
If net inward current is less than net outward current, the membrane will not be depolarized to threshold, and no action potential will occur.
Polarization
Any time the value of the membrane potential is other than 0 mV, in either the positive or negative direction, the membrane is in a state of polarization a state in which membrane is polarized at rest, negative inside and positive outside
Graded potentials occur when chemical signals from other neurons open chemically gated ion channels, allowing ions to enter or leave the neuron
Graded potentials may also occur when an open channel closes, decreasing the movement of ions through the cell membrane. For example, if K* channels close, fewer K* leave the cell, and the retention of K* depolarizes the cell.
Inactivation gates
Voltage-dependent
Closes with depolarization
Opens with hyperpolarization ????
Time-dependent (slow)
1. Absolute refractory period
- During the time interval between the opening of the Na+channel activation gate and the opening of the inactivation gate, a Na+ channel CANNOT be stimulated.
- A Na+ channel cannot be involved in another AP until the inactivation gate has been reset.
-Axon membrane is incapable of producing another AP
is the period during which another action potential cannot be elicited, no matter how large the stimulus
A relative refractory period follows the absolute refractory
period. During the relative refractory period, some but not all
Na* channel gates have reset to their original positions. Those
Na* channels that have not quite returned to their resting position
can be opened by a higher-than-normal graded potential,
which has the effect of moving the threshold value closer to
zero. This means that a stronger-than-normal depolarizing
graded potential is needed to bring the cell up to threshold.
In addition, during the relative refractory period, K* channels
are still open. Although Na* can enter through newly reopened
Na* channels, depolarization due to Na* entry will be
offset by K* loss. As a result, any action potentials that re have
a smaller amplitude than normal
All-or-None" Law
It is possible to determine the minimal intensity of stimulating current (threshold intensity) that, acting for a given duration, will just produce an action potential. The threshold intensity varies with the duration; with weak stimuli it is long, and with strong stimuli it is short. The relation between the strength and the duration of a threshold stimulus is called the strength–duration curve. Slowly rising currents fail to fire the nerve because the nerve adapts to the applied stimulus, a process called adaptation.
Once threshold intensity is reached, a full-fledged action potential is produced. Further increases in the intensity of a stimulus produce no increment or other change in the action potential as long as the other experimental conditions remain constant. The action potential fails to occur if the stimulus is subthreshold in magnitude, and it occurs with constant amplitude and form regardless of the strength of the stimulus if the stimulus is at or above threshold intensity. The action potential is therefore "all or none" in character and is said to obey the all-or-none law.
Electrotonic Potentials, Local Response, & Firing Level= graded potential
Although subthreshold stimuli do not produce an action potential, they do have an effect on the membrane potential. This can be demonstrated by placing recording electrodes within a few millimeters of a stimulating electrode and applying subthreshold stimuli of fixed duration. Application of such currents leads to a localized depolarizing potential change that rises sharply and decays exponentially with time. The magnitude of this response drops off rapidly as the distance between the stimulating and recording electrodes is increased. Conversely, an anodal current produces a hyperpolarizing potential change of similar duration. These potential changes are called electrotonic potentials. As the strength of the current is increased, the response is greater due to the increasing addition of a local response of the membrane (Figure 4–8). Finally, at 7–15 mV of depolarization (potential of –55 mV), the firing level is reached and an action potential occurs.
Why do graded potentials lose strength as they move
through the cytoplasm? There are two reasons:
1. Current leak. Some of the positive ions leak back across the
membrane as the depolarization wave moves through the
cell. The membrane in the neuron cell body is not a good
insulator and has open leak channels that allow positive
charge to ow out into the extracellular uid.
2. Cytoplasmic resistance. The cytoplasm itself provides resistance
to the ow of electricity, just as water creates resistance
that diminishes the waves from the stone. The combination
of current leak and cytoplasmic resistance means that the
strength of the signal inside the cell decreases over distance.
Nodes of Ranvier
• Only region where current flow across the membrane exist.
• Region of concentrated voltage-gated Na channels.
There are 3 types of neuroneuronal junctions
1. Axo-dendritic junctions[most commen]
2. Axo-somatic junctions
3 Axo-axonic junctions
Electrical synapses
Allow current to flow from one excitable cell to the next via low resistance pathways between the cells called gap junctions(b/n the pre- and postsynaptic neurons)