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03/19/17 1
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
03/19/17 2
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
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
03/19/17
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
 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
03/19/17 5
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
603/19/17
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
03/19/17 7
Levels of the Organization of the Human Body
 chemical level cell  tissue organ  system organism
03/19/17 8
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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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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 There are many different types of cells in the body including:
Nerve cells
Blood cells
Epithelial cells and
Muscle cells
03/19/17 11
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.
03/19/17 12
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
03/19/17 13
5. organism –it is the highest level of organization.
e.g human
03/19/17 14
CVS GIT RS
Renal
System
Skeletal
System
Muscular
system
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
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
 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.
03/19/17
03/19/17 18
Cardiovascular System(CVS)
CVS-provides
nutrients(glucose,aa,lipids),
gases (O2)
signaling molecules
(hormones) and
Removal of wastes (urea,
creatinine, CO2),
 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
1903/19/17
 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.
2003/19/17
03/19/17 21
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
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).
03/19/17
23
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
To stabilize the physiological factor being regulated,
homeostatic control systems must be able to detect and
resist change.
03/19/17 24
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
03/19/17 25
• 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.
03/19/17 26
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
03/19/17 27
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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03/19/17 29
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
3003/19/17
 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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Control of Blood Glucose Level
33
Ca2+-
homeostasis
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Control of Arterial Blood Pressure
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
03/19/17
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.
03/19/17
PFM..
1. Blood clotting is an example of a very valuable use of PFM.
3703/19/17
2. Labor during child birth
3803/19/17
39
PFM..
03/19/17
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
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
03/19/17 40
 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.
4103/19/17
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
03/19/17
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
03/19/17 44
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
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
03/19/17
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
Cell Physiology
» Two types of cells:
A. cells without typical nucleus = prokaryotes
B. cells with nucleus = eukaryotes
4703/19/17
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
03/19/17 48
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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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.
03/19/17
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.
03/19/17
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
03/19/17 52
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).
03/19/17
03/19/17 54
Cell organelles may be:
Non-membrane-limited
Nucleoli
Ribosomes
Microtubules
Microfilaments
Centrioles
Membrane-limited
Nucleus
Endoplasmic reticulum
 Golgi apparatus
Lysosomes
Mitochondria
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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
03/19/17
57
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
03/19/17
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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)
03/19/17
59
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.
03/19/17
60
Rough ER and Golgi complex
03/19/17
61
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
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.
6203/19/17
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.
6303/19/17
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
6403/19/17
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
6503/19/17
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
67
Intercellular signaling
03/19/17
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
03/19/17 68
03/19/17 69
03/19/17 70
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
03/19/17 71
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.
03/19/17
72
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
7303/19/17
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
03/19/17 74
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
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)
03/19/17
7703/19/17
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
03/19/17 78
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
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).
8003/19/17
ICF
Water
High K+,Po4
3-
,Mg2+,
proteins
Nutrients,
gases
Hormones
ECF
Water
High Na+
, Cl-
, Ca2+
and
HCO3
Nutrients
Gases: O2, CO2
Hormones
Enzymes
81
Special mechanisms for transporting ions through the cell
membranes maintain the ion concentration differences between the
extracellular and intracellular fluids.
03/19/17
Normal values of ECF & ICF
03/19/17 82
 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)
8303/19/17
Disturbances of Water Balance
• Disturbances of body fluid volume may be
hypervolemia (excess fluid retention) or
 hypovolemia (loss of fluid or dehydration)
8403/19/17
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
8503/19/17
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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Membrane Physiology
87
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
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
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
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
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
Phospholipids
Fatty acid
Phosphate
• Phosphate head
– hydrophilic
• Fatty acid tails
– hydrophobic
• Arranged as a bilayer “repelled by water”
“attracted to water”
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
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
• 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
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.
 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
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.
100
101
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
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
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
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
Transport through the cell membrane
II. The movement of large molecules across cell membrane
takes place by vesicular transport
1. Endocytosis
2. Exocytosis
106
107
Transport through the cell membrane
ECF
ICF
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
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
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
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
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:
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
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
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
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
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.
Importance of Na+
-K+
Pump
Creates an electrical potential across the cell
membrane
118
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 .
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
 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
122
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
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.
phagocytosis
pinocytosis
receptor-mediated
endocytosis
fuse with
lysosome for
digestion
non-specific
process
triggered by
molecular signal
125
C. Receptor-mediated endocytosis
Requires the substance to bind to a membrane-
bound receptor
126
2. Exocytosis - “Cell vomiting”
E.g. Releases of NTs, digestive
enzymes and some hormones.
127
Resting Membrane Potential
128
Tissues which are capable of generation and
transmission of electrochemical impulses
along the membrane
E.g.- nerve and muscle
129
Excitable Tissues
• Neurons are functional & structural units of
the nervous system.
• Specialized to conduct information from one
part of the body to another
130
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
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
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

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
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
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
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.
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
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
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
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
• 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
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.
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
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
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
 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
148
Phases of action
potential:
1. Resting phase
2. Depolarization
3. Repolarization
149
2 gates
1. Activation gates
Voltage-dependent
Opens with
depolarization
Fast opening
––
1
Voltage-Gated Na+
Channels
150
2. Inactivation gates
 Voltage-dependent
Closes with depolarization
Slow opening
Voltage-Gated Na+
Channels
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
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.
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
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
 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
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
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
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
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)
160
Saltatory Conduction
 Nodes of Ranvier
• Region of concentrated voltage-gated Na channels.
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
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
 There are 3 types of neuroneuronal junctions
1. Axo-dendritic junctions
2. Axo-somatic junctions
3 Axo-axonic junctions
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
Electrical synapses…
Characteristics
Are extremely rapid,
relatively rare and
have very little physiological
significance .
An AP in one neuron always
leads to an AP in the
connected neuron
165
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
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
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
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
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
171
Excitatory Synapses Inhibitory Synapses
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
173
PH
- Alkalosis ↑ Synaptic transmission
- Acidosis ↓ Synaptic transmission
Hypoxia ↓ Synaptic transmission
Drugs
- Caffeine, Theophylline, Theobromine
↑Synaptic transmission
- Strychnine
↑ Synaptic transmission
- Hypnotics, Anesthetics, tranquilizers
↓ Synaptic transmission
Factors Affecting Synaptic transmission
THANK YOU!!
174

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Introduction to physiology yy

  • 1. 03/19/17 1 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
  • 2. 03/19/17 2 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 03/19/17
  • 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 03/19/17 5
  • 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 603/19/17
  • 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 03/19/17 7
  • 8. Levels of the Organization of the Human Body  chemical level cell  tissue organ  system organism 03/19/17 8
  • 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. 03/19/17 9
  • 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. 03/19/17 10
  • 11.  There are many different types of cells in the body including: Nerve cells Blood cells Epithelial cells and Muscle cells 03/19/17 11
  • 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. 03/19/17 12
  • 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 03/19/17 13
  • 14. 5. organism –it is the highest level of organization. e.g human 03/19/17 14 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 03/19/17 16
  • 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. 03/19/17
  • 18. 03/19/17 18 Cardiovascular System(CVS) CVS-provides nutrients(glucose,aa,lipids), gases (O2) signaling molecules (hormones) and Removal of wastes (urea, creatinine, CO2),
  • 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 1903/19/17
  • 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. 2003/19/17
  • 21. 03/19/17 21 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). 03/19/17
  • 23. 23 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. 03/19/17 24
  • 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 03/19/17 25
  • 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. 03/19/17 26
  • 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 03/19/17 27
  • 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 03/19/17
  • 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 3003/19/17
  • 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. 3103/19/17
  • 32. 03/19/17 32 Control of Blood Glucose Level
  • 34. 03/19/17 34 Control of Arterial Blood Pressure
  • 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 03/19/17
  • 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. 03/19/17
  • 37. PFM.. 1. Blood clotting is an example of a very valuable use of PFM. 3703/19/17
  • 38. 2. Labor during child birth 3803/19/17
  • 39. 39 PFM.. 03/19/17 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 03/19/17 40
  • 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. 4103/19/17
  • 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 03/19/17
  • 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
  • 44. 03/19/17 44 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 03/19/17
  • 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 4703/19/17
  • 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 03/19/17 48
  • 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. 03/19/17
  • 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. 03/19/17
  • 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. 03/19/17
  • 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 03/19/17 52
  • 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). 03/19/17
  • 55. Cell organelles may be: Non-membrane-limited Nucleoli Ribosomes Microtubules Microfilaments Centrioles Membrane-limited Nucleus Endoplasmic reticulum  Golgi apparatus Lysosomes Mitochondria 03/19/17 55
  • 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 03/19/17
  • 57. 57 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 03/19/17
  • 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) 03/19/17
  • 59. 59 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. 03/19/17
  • 60. 60 Rough ER and Golgi complex 03/19/17
  • 61. 61 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. 6203/19/17
  • 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. 6303/19/17
  • 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 6403/19/17
  • 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 6503/19/17
  • 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 03/19/17 68
  • 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 03/19/17 71
  • 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. 03/19/17 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 7303/19/17
  • 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 03/19/17 74
  • 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 03/19/17 75
  • 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) 03/19/17
  • 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 03/19/17 78
  • 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). 8003/19/17
  • 81. ICF Water High K+,Po4 3- ,Mg2+, proteins Nutrients, gases Hormones ECF Water High Na+ , Cl- , Ca2+ and HCO3 Nutrients Gases: O2, CO2 Hormones Enzymes 81 Special mechanisms for transporting ions through the cell membranes maintain the ion concentration differences between the extracellular and intracellular fluids. 03/19/17
  • 82. Normal values of ECF & ICF 03/19/17 82
  • 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) 8303/19/17
  • 84. Disturbances of Water Balance • Disturbances of body fluid volume may be hypervolemia (excess fluid retention) or  hypovolemia (loss of fluid or dehydration) 8403/19/17
  • 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 8503/19/17
  • 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 8603/19/17
  • 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
  • 93. Phospholipids Fatty acid Phosphate • Phosphate head – hydrophilic • Fatty acid tails – hydrophobic • Arranged as a bilayer “repelled by water” “attracted to water”
  • 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.
  • 100. 100
  • 101. 101
  • 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
  • 107. 107 Transport through the cell membrane ECF ICF
  • 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.
  • 118. Importance of Na+ -K+ Pump Creates an electrical potential across the cell membrane 118
  • 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
  • 122. 122
  • 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.
  • 125. phagocytosis pinocytosis receptor-mediated endocytosis fuse with lysosome for digestion non-specific process triggered by molecular signal 125 C. Receptor-mediated endocytosis Requires the substance to bind to a membrane- bound receptor
  • 126. 126 2. Exocytosis - “Cell vomiting” E.g. Releases of NTs, digestive enzymes and some hormones.
  • 127. 127
  • 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
  • 148. 148 Phases of action potential: 1. Resting phase 2. Depolarization 3. Repolarization
  • 149. 149 2 gates 1. Activation gates Voltage-dependent Opens with depolarization Fast opening –– 1 Voltage-Gated Na+ Channels
  • 150. 150 2. Inactivation gates  Voltage-dependent Closes with depolarization Slow opening Voltage-Gated Na+ Channels
  • 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)
  • 160. 160 Saltatory Conduction  Nodes of Ranvier • Region of concentrated voltage-gated Na channels.
  • 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
  • 165. Electrical synapses… Characteristics Are extremely rapid, relatively rare and have very little physiological significance . An AP in one neuron always leads to an AP in the connected neuron 165
  • 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
  • 173. 173 PH - Alkalosis ↑ Synaptic transmission - Acidosis ↓ Synaptic transmission Hypoxia ↓ Synaptic transmission Drugs - Caffeine, Theophylline, Theobromine ↑Synaptic transmission - Strychnine ↑ Synaptic transmission - Hypnotics, Anesthetics, tranquilizers ↓ Synaptic transmission Factors Affecting Synaptic transmission

Editor's Notes

  1. 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.
  2. 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.
  3. 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.
  4. 200 different types of cells RBC= 25 trillion cells
  5. 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
  6. 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.
  7. Read page 7 0f gytun new edition
  8. 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.
  9. II. Feedback control The body organs receive information (feedback) about the extent of their activities through the regulatory mechanisms (NS or ES).
  10. 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.
  11. 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
  12. 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.
  13. 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.
  14. 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
  15. The function of rER is to segregate/isolate proteins that are being exported from the cell.
  16. ATP It is energy rich compound required for various cellular activities
  17. Juxtacrine signals are transmitted along cell membranes via protein or lipid components integral to the membrane and
  18. Adherens Junctions They seem to be responsible for contact inhibition
  19. 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).
  20. 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.
  21. 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.
  22. Peripheral proteins that are present only on one side of the membrane, serve primarily as enzymes ??????
  23. CHO-antigenic activity in ABO blood groups (immune reaction ,antigenical importance) ?????
  24. Factors affecting the net rate of diffusion Electrical potential difference of ions ???
  25. 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.
  26. 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.
  27. 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.
  28. Tonicity is the osmolality of a solution relative to osmolality of plasma
  29. 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)
  30. 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.
  31. 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.
  32. 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.
  33. b. Pinocytosis- cell drinking : e.g. absorption of undigested protein in gut of newborns.
  34. 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.
  35. 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.???????
  36. 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.
  37. 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).
  38. If net inward current is less than net outward current, the membrane will not be depolarized to threshold, and no action potential will occur.
  39. 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
  40. 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.
  41. Inactivation gates Voltage-dependent Closes with depolarization Opens with hyperpolarization ???? Time-dependent (slow)
  42. 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
  43. is the period during which another action potential cannot be elicited, no matter how large the stimulus
  44. 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
  45. 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.
  46. 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.
  47. Orthodromic Vs antidromic Conduction Orthodromic conduction Soma Axon terminal Antidromic conduction Axon terminal Soma
  48. Nodes of Ranvier • Only region where current flow across the membrane exist. • Region of concentrated voltage-gated Na channels.
  49. There are 3 types of neuroneuronal junctions 1. Axo-dendritic junctions[most commen] 2. Axo-somatic junctions 3 Axo-axonic junctions
  50. 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)
  51. GABA(,Gamma –aminobutyric acid)