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By:
Zewdu Minwuyelet (MSc in Medical Physiology, MPH in PH Epidemiology)
Email: zwdminwuyelet@gmail.com
Phone No-: +251 985898219
Ethiopian Police University
Department of Nursing
Human Physiology
Addis Ababa, Ethiopia
Nov, 2023/24
2
Course Description
Course name: Human Physiology =
==========================================
This course is designed to equip students with the basic concepts of human
physiology. This course covers the physiology of humans, with emphasis on the
major organs and systems and the physiological processes which govern heart beat
and cardiac output, circulation, movement, plasma volume and osmoregulation,
energetics and temperature regulation, respiration, digestion and reproduction.
3
Course contents
Ch-1 Introduction & cell Physiology
Ch-2 Excitable cells & membrane potentials
Ch-3 Musculo-skeletal System
Ch-4 Autonomous Nervous system
Ch-5 Blood Physiology
Ch-6 Cardio-vascular System
Ch-7 Respiratory system Physiology
Ch-8 Gastrointestinal system Physiology
Ch-9 Renal system Physiology
Ch-10 Reproductive system Physiology
Ch-11 Endocrine system Physiology
Ch-12 Nervous system Physiology
4
Teaching Methods
❖ The teaching methods will be either of the following:
Lecture/discussion
Assignments
• Group work/seminar
• Independent studies
5
Assessment Methods
❖ The teaching methods will be either of the following:
Class room activity and attendance
Written assignment and presentation
Written examination (mid & final examinations)
6
Introduction & Cell Physiology
7
Introduction & Cell Physiology
Contents
♠ Historical background of Physiology
♠ Levels of structural organization of the human body
♠ Cells and its function ( diversity, cell theory, types, its organizations,
organel function)
♠ body fluids & the internal environment
♠ The role of electrolytes in signaling
♠ Clinical correlates of body fluids & electrolytes
♠ Homeostasis ( definition, types & mechanisms)
♠ Membrane transport
Historical Background & Definition of Physiology
❖ Aristotle (384 - 322 B.C.) was regarded as:
➢The father of natural history &
the 1st person to coin the term Physiology.
➢ According to Aristotle, physiology meant the study of nature .
- “Physio- nature, logy– study”, i.e. studying
practically everything in the universe & in the human body.
8
Chapter I: Introduction & Cell Physiology
❖ Modern definition of Physiology:
✓ is the scientific study of normal body functions.
✓ It deals with the physical & chemical processes in cells and
tissues to elaborate performances of the organism.
✓ Some of these physiological processes includes:
- the mechanisms by which impulse transmission of nerves
from one part of the body to another,
- movement of the body (contraction of skeletal muscles),
- the mechanisms by which the organism sees, hears, smells,
digests, keeps warm, etc.
- Reproduction,………..+
9
Chapter I: Introduction & Cell Physiology
Levels of structural organization of the human body
1
2
4
5
6
3
Smooth muscle cell
Molecules
Atoms
Smooth
muscle
tissue
Epithelial
tissue
Heart
Blood
vessels
Smooth
muscle
tissue
Connective
tissue
Blood
vessel
(organ)
Cardiovascular
system
Cellular level
Cells are made up of
molecules.
Tissue level
Tissues consist of
similar types of cells.
Organ level
Organs are made up
of different types
of tissues. Organ system level
Organ systems consist of
different organs that
work together closely.
Organism level
The human organism
is made up of many
organ systems.
Chemical level
Atoms combine to
form molecules.
10
Chapter I: Introduction & Cell Physiology
A. Atoms & molecules
• At its simplest level, the body is composed of atoms.
• The most common atoms/elements in the human body are:
- Carbon - Nitrogen
- Hydrogen - Phosphorus
- Oxygen - Sulpher
• A combination of atoms molecules/compounds
Macromolecules.
(Organic & inorganic molecules )
11
Chapter I: Introduction & Cell Physiology
12
❖ Organic substances:
✓ Carbohydrates (like glycogen, starch, & glucose..…),
Lipids (fats)
Proteins, &
Vitamins.
❖ Inorganic substances:
✓ Water (a universal solvent, contribute to hydrolysis rxn)
✓ Salts
✓ Dissolved inorganic ions (electrolytes…Na+, K +, Ca2+, HCO3
✓ Minerals
✓ Blood gases…
Chapter I: Introduction & Cell Physiology
13
Chapter I: Introduction & Cell Physiology
B. Cells
❖ are basic structural & functional units of human body/life
❖ are living units
❖ Have 4 principal parts
a)Plasma membrane
b)Cytosol /ICF
c)Organelles
d)Inclusions
14
Chapter I: Introduction & Cell Physiology
B. Tissues
❖ Are group of cells which perform a specific function
❖ are 4 different major types
a) Connective tissue
b) Epithelial tissue
c) Muscle tissue
d) Nerve tissue
15
Chapter I: Introduction & Cell Physiology
C. Organs
❖ Are group of two or more different tissues which perform a
specific function
❖ Examples:
a) Heart
b) Blood vessels
c) Brain
d) Spinal cord
e) Stomach
f) Small intestine…..
16
Chapter I: Introduction & Cell Physiology
D. Systems
❖Consist of organs that provide a common/related function
❖Examples:
a) Cardiovascular system
b) Respiratory system
c) Nervous system
d) Gastrointestinal system
17
Chapter I: Introduction & Cell Physiology
E. Organismal Level
❖ All systems of the body functioning
with another comprise the total organism.
❖Examples: human being
2. Cells & its function
• Cell is the smallest unit of life.
• All life depends on the many chemical activities of cells.
-Different cells perform different activity.
• Each organ is an aggregate of many different cells held
together by intercellular supporting structures (≈ 100 trillion cells)
• Each type of cell is specially adapted to perform one or a few particular functions.
➢ Cells are highly specialized both in structure & function.
For e.g., the RBCs, numbering 25 trillion in each human being, responsible to
transport blood gases (oxygen & carbondioxide).
18
Chapter I: Introduction & Cell Physiology
Fig… Structure of the cell 19
✓Even though cells are highly specialized both in structure & function, most of
them share similar features (organelle), which has similar function in different cells
Chapter I: Introduction & Cell Physiology
20
✓ Diversity of Cells: cells are highly specialized both in structure & function
Chapter I: Introduction & Cell Physiology
Cell Theory
✓ Cells are the structural and functional unit of life.
- A cell is the smallest biological unit of living matter.
✓ All organisms are composed of cells.
- Be it multicellular or unicellular
✓ Cells come only from pre-existing cells (self-replicating unit ).
21
Chapter I: Introduction & Cell Physiology
Prokaryotic cells Eukaryotic cells
✓ Lacks a well-defined nucleus, &
✓ have a relatively simple internal
organization.
Have advanced & larger nucleus &
has more complex internal organization.
✓ Have no membrane-bound organelles. Have many membrane-bound
organelles with specialized functions
✓ have circular DNA with
out protein in the cytoplasm
Have linear chromosomes
✓ have smaller ribosomes have larger ribosomes
✓ have no cytoskeleton have cytoskeleton elements:
- microtubules, microfilaments
& intermediate filaments
✓ always found in unicellular
organisms e.g. Bacteria.
✓found in multi-cellular
organisms e.g. Animal & plant cells
Types of Cells
Chapter I: Introduction & Cell Physiology
Organization of the cell
❖ Each eukaryotic cell has three common components:
1. Plasma membrane (cell membrane)
2. Cytoplasm containing organelles
3. Nucleus/region containing DNA
23
Chapter I: Introduction & Cell Physiology
The cell organelles
❖ Include
✓ Cell membrane
✓ Nucleus
✓ Ribosomes
✓ Endoplasmic reticulum
✓ Golgi complex
✓ Mitochondria
✓ Lysosomes…….
24
Chapter I: Introduction & Cell Physiology
1. Plasma (cell) membrane
✓ A membrane that separates the interior of the cell (ICF ) from ECF environment.
✓ cell membrane is composed of double layer of phospholipids in which proteins are
embedded that contribute specialized functions to the cell.
✓ it determines what can enter & leave the cell
Fluid Mosaic Model:
✓ Protein molecules bobbing/floating in phospholipids sea &
determine membrane’s specific functions.
✓ the cell membrane moves freely because of its oily nature (fluid)
25
Chapter I: Introduction & Cell Physiology
✓The plasma membrane is a fluid combination of PL, cholesrtol, & proteins.
26
Chapter I: Introduction & Cell Physiology
Phospholipids bilayer
✓ Polar heads, outside & inside: hydrophilic head, attract water
✓ Nonpolar tails in the interior: hydrophobic tail, repel water
27
Chapter I: Introduction & Cell Physiology
28
Functions of the CM:
1. Regulate the passage of substances into and out of cells
2. Detect chemical messengers arriving at the cell surface or acts as receptors for
signal transduction
3. Anchor cells to the extracellular matrix
4. Separates ICFs from ECFs.
5. Enzymatic activity (contain membrane bound enzyme)
6. Attachment to cytoskeleton elements.
Chapter I: Introduction & Cell Physiology
29
▪ Proteins in the cell membrane determine membrane’s specific functions.
Because these membrane proteins act as:
a. Ion channels / integral membrane proteins:
✓ water filled channels that allow for the transport of ions across the plasma
membrane.
1. Non-gated/open /leaky /resting channels: ------open at rest
2. Gated channels…….closed at rest & open to application of stimulus.
i. Ligand-gated ….open in response to chemicals such as drugs,
neurotransmitters & hormones.
ii. Voltage –gated…open in response to change of membrane
potential/depolarization.
iii. Mechanically-gated…open in response to physical deformation.
Chapter I: Introduction & Cell Physiology
30
2. Gated channels…….closed at rest & open to application of stimulus.
i. Ligand-gated ….open in response to chemicals
ii. Voltage –gated…open in response to change of membrane potential.
iii. Mechanically-gated…open in response to physical deformation.
Chapter I: Introduction & Cell Physiology
31
b. Membrane bound enzymes: that catalyses certain chemical reactions on the
surface of target tissues.
e.g. Phospholipase C (PLC), Adenylyl cyclase…. etc.
c. Ion pumps: that transport ions against concentration gradient with the
utilization of energy/ATP.
e.g. Na/K pump/ Na/K ATPase…
d. Receptors: forms binding site to hormones, neurotransmitters & drugs.
e. Antigens:
Chapter I: Introduction & Cell Physiology
✓Lipid bilayer of the plasma membrane, with various membrane proteins that
serve transport and signaling functions.
32
Chapter I: Introduction & Cell Physiology
2. The nucleus
33
✓ Controls the cell, houses the genetic material (DNA).
✓ It is the largest organelle of the cell.
✓ Cells may have one nucleus or more than or lack a nucleus at all. e.g.
➢ Skeletal muscle cells contain more than one nucleus.
➢ Mature RBCs have no nucleus.
➢ Cardiac cells contain only one nucleus.
Function:
❖ controls and directs all activities of cells.
❖ contains nucleic acids (DNA + RNA)
Chapter I: Introduction & Cell Physiology
The nucleus cont’d
✓ Composed of:
▪ Nuclear envelope
▪ Nucleolus
▪ Chromatin
34
Chapter I: Introduction & Cell Physiology
35
Nucleus
components
Structure Function
Nuclear envelope ✓ Double layer membrane
that surrounds the
nucleus, composed of
lipids & proteins
molecules
➢ Supports the nucleus
➢ Controls passage of
materials between the
cytoplasm & the
nucleoplasm
Nucleolus ✓ Dense nonmembraneous
mass composed of proteins
& RNA molecules
➢ Produces ribosomal
RNA
Chromatin ✓ Fibrous strands
composed of proteins
& DNA.
➢ Contains genetic code
that determines which
proteins will manufactured
by the cell
Chapter I: Introduction & Cell Physiology
36
3. Ribosomes
✓ Are granular particles composed of proteins & RNA
✓ found both free in the cytoplasm and on the surface of the ER.
Function
✓ are often called the “protein factories” of the cell
➢ Free ribosomes: ribosomes which are free within the cytoplasm.
Function: synthesizes soluble proteins.
- Site at which amino acids are assembled into proteins.
➢ Membrane-bound ribosomes: ribosomses embedded on the
surface of endoplasmic reticulum (RER)
Function: synthesizes proteins to be incorporated
into membranes.
Chapter I: Introduction & Cell Physiology
37
Chapter I: Introduction & Cell Physiology
38
4. Endoplasmic Reticulum (ER)
✓ It is an interconnected tubular structures which is continuous with the nuclear
membrane.
✓ The ER may be either of two types:
(1) Granular, or rough ER:
✓ assists in protein synthesis
(2) Agranular, or smooth ER.
✓serves a variety of purposes in different cells;
In striated muscle cells: it stores Ca2+
In the testes - it provides a site for enzyme reactions in
steroid hormone synthesis.
In the intestinal cells – absorption, synthesis,
& transport of fats
Chapter I: Introduction & Cell Physiology
39
5. Golgi apparatus
✓ Cluster of flattened membranous sacs.
✓ It is the central delivery system of the cell.
✓ It "Packages" cellular products in sacs (vesicles) & move it to
designated parts of the cell.
Function:
▪ modification, concentration of protein products prior to secretion.
▪ transporting of cellular products to the desired/designated parts of the cell.
Chapter I: Introduction & Cell Physiology
40
6. Lysosomes:
✓ Are spherical membranous bags containing a number of powerful
digestive enzymes.
✓ They contain > 40 types of hydrolytic enzymes.
➢These enzymes are all acid hydrolases (they function best
at the acidic pH of the lysosomal compartment).
Function:
▪ Digest ingested bacteria, viruses, and toxins
▪ Degrade nonfunctional organelles
Chapter I: Introduction & Cell Physiology
41
7. Centrioles
✓ Two small cylindrical bodies composed of nine sets of three
fused microtubules.
✓ located near nucleus
Function:
➢Formation of spindle apparatus at poles of cell
during cell division.
Chapter I: Introduction & Cell Physiology
42
8. Mitochondria
✓ Are the organelles that function as the "powerhouse of the cell”, generating ATP,
the universal form of energy used by all cells.
✓ Serve as site for the production of most of the energy of cell.
✓ It converts food nutrients such as glucose, to a fuel (ATP) that the cells of the body
can use.
✓ Mitochondria are unique in that they have their own mitochondrial DNA
(separate from the DNA that is in the nucleus).
Function:
✓ Site of aerobic cellular respiration
✓ Contains enzymes of krebs cycle & oxidative phosphoryiation
✓ Breaks down food to make ATP
Chapter I: Introduction & Cell Physiology
43
Structure of mitochondria
Chapter I: Introduction & Cell Physiology
44
Body fluids & the internal environment/ ECF
✓ The ions & nutrients in the ECF are needed by the cell to maintain its life.
✓ Cells are capable of living, growing, and performing their special
functions as long as the proper concentrations of oxygen,
glucose, different ions, amino acids, fatty substances, and
other constituent are available in this internal environment.
➢ Thus, “all cells live in essentially in the same environment”—the
extracellular fluid (ECF). For this reason, the ECF is also
called the internal environment of the body, or the milieu intérieur
(a term introduced more than 100 years ago by the great 19thC
French physiologist Claude Bernard).
Chapter I: Introduction & Cell Physiology
45
• About 60 % of the adult human body is fluid, mainly water solution of ions &
other substances.
• Although most of this fluid is occur inside the cells &
it is called ICF, about one third is in the spaces outside
the cells and it is called ECF.
• Thus, the total body fluid is distributed mainly in b/n two
fluid compartment i.e. ECF and ICF.
Body Fluids
Chapter I: Introduction & Cell Physiology
46
Fluid compartments
ECF= Plasma & IFs
✓ Water (1/3)
✓ High Na+, Cl- , Ca2+ and HCO3
-
✓ Nutrients: glucose, a.a, fatty acids
✓ Gases: O2, CO2
✓ Hormones
✓ Enzymes
▪ Both fluid compartments have their fluid volume & composition essentially
kept constant for the cell to plod on undisturbed.
• High-water (2/3)
• High K+, PO4
3 - Mg2+
• Nutrients, gases
• Hormones
• Enzymes
ICF
Chapter I: Introduction & Cell Physiology
47
Chapter I: Introduction & Cell Physiology
48
Cat ions:
- Major cat ion in ECF= Na+
✓ most of the time, responsible for depolarization phase of AP in excitable cells
- Major cat ion in ICF = K+
✓ most of the time, responsible for repolarization phase of AP in excitable cells
✓ Na-K pump in cells of mammals helps to:
Push out Na that enters into cells.
Push in K that leave out of cells.
(To regain RMP of excitable cells)
Anions:
- major anion in ECF- Cl- (responsible for hyper polarization)
- major anion in ICF: fixed anions (large organic molecules: i.e.
Proteins, nucleotides, polyphosphates within cell.
- Proteins with phosphates remaining inside cell because they are
too large to diffuse out (fixed anions)
Chapter I: Introduction & Cell Physiology
49
Chapter I: Introduction & Cell Physiology
50
Clinical Correlates on cellular environment
❖ Edema : accumulation of water & solutes in the IF compartment.
❖ Types
1. Pitting edema: if firm finger tip pressure on swollen area leaves a depression.
2. Non-pitting edema: edema with lack of indentation
when finger tip pressure is applied to the skin.
✓ It can occur in certain disorders of the lymphatic
system such as lymphedema & hypothyroidism conditions.
❖ Generalized edema (Anasarca)
Reasons: ✓ Expanded IF volume.
✓ Total body sodium.
Chapter I: Introduction & Cell Physiology
51
❖ Cellular edema: is caused by the entry of water into the cells,
inducing them to swell.
➢ This may occur because of
Decreased osmolality of the fluid surrounding the cells,
as in hypotonic fluid overload, or
e.g. RBC in hypotonic solution→ Swelled & burst.
Increased osmolality of the intracellular fluid, as in
conditions that decrease the activity of the Na-K
pump of the cell membrane, allowing the concentration
of sodium ions within the cell to be increased.
Chapter I: Introduction & Cell Physiology
52
✓ Some mechanisms of Cellular edema:
i. Depression of cellular metabolism → ↓Na+-K+ pump → ↑[Na+] inside the cell
→Water moves to Na+→ Cellular edema.
ii. Inflammation→↑membrane permeability to sodium
& other ions that diffuse into cell with
water→ cellular edema.
Chapter I: Introduction & Cell Physiology
53
❖ Water intoxication:
✓ Occurs when excessive volumes of water are absorbed
too quickly leading to nausea, vomiting & shock
conditions.
✓ These are caused by undue drop in plasma osmolarity
before adequate inhibition of ADH secretion occurs.
Chapter I: Introduction & Cell Physiology
54
What is homeostasis?
❖ Homeostasis, is derived from the two Greek words “homeo” =same & “stasis”
=steady, refers to any process that living things use actively to maintain fairly stable
conditions necessary for survival.
❖ Claude Bernard :The father of modern Physiology;
According to him homeostasis defined as:
• The internal environment remains relatively in a constant state though there are
changes in the external environment.
• Constant,stable, ≠ rigidity, can vary within narrow limit (i.e. normal physiological
range)
Chapter I: Introduction & Cell Physiology
55
✓ All body systems working together to maintain a stable internal environment, responds
to external & internal changes to function within a normal ranges.
✓ The internal environment of the body is in a dynamic state of equilibrium
(continuously es with in normal physiological ranges)
✓ Homeostasis involves dynamic mechanisms that detect & respond to deviations in
physiological variables from their “set point” values.
✓ Failure to function within a normal range results into disease condition.
Chapter I: Introduction & Cell Physiology
56
Set point values
Controlled variables
Chapter I: Introduction & Cell Physiology
57
✓ Normal ranges of some controlled variables
Arterial pH 7.35 - 7.45
Glucose 75 -125 mg/100 ml
Total lipid 400-800 mg/100 ml
O2 content 17.2 - 22 ml/100 ml
Bicarbonate 24 - 28 mEq/L
Chapter I: Introduction & Cell Physiology
58
✓ Homeostasis is continually being disrupted by:
External stimuli: change in
Environmental T° (heat & cold), PaO2, pathogens, toxins, etc.…
Internal stimuli: change in
pH…affects metabolic rate
Blood pressure…affects other body systems activity.
[ ] of water, glucose, salts, oxygen, …etc
Chapter I: Introduction & Cell Physiology
59
• Successful compensation
➔ Homeostasis reestablished
➢ wellness
• Failure to compensate
➔ Pathophysiology
➢Illness
➢Disease/Death
Homeostasis is continually being disrupted by Internal & external changes
Chapter I: Introduction & Cell Physiology
60
✓ There are more than10 body systems, each has unique contributions to keep normal
body function.
✓ However, it is the integration of all the body systems that allows the creation of a
stable internal environment in which cells are able to function.
For example, the maintenance of normal BP requires the integration of several organ
systems including the ANS (NS), endocrine system, the CVS, renal & GI systems.
Chapter I: Introduction & Cell Physiology
61
✓ The major determinants of BP in the CVS are the cardiac output
& the vascular resistance.
✓ The volume of blood is also a key determinant of BP controlled by a balance
between fluid & salt intake, via the gastrointestinal system & their excretion via
the renal system.
✓ Appetite & thirst are controlled by the nervous system, and also enhanced
by the endocrine system (leptin & gherlin) integrates the activity of all
body systems.
✓The golden goal of every organ is to maintain homeostasis.
Chapter I: Introduction & Cell Physiology
62
Nervous system Endocrine system
• By means of electric impulses
(AP) & chemical release
(neurotransmitters).
By release hormones to the blood stream
system, where it transported to target
tissues .
• The transmission of information
is very rapidly & immediate effect
(within milliseconds) e.g. reflex.
The transmission of information is very
slowly. More wide spread & longer lasting
effect. e.g. growth of the body
• Responds to the internal &
external changes, involved for
homeostasis function.
Involved in more generalized effect, on
activities such as growth, metabolism &
reproduction etc.
❖ mainly two systems that maintain homeostasis are:
Chapter I: Introduction & Cell Physiology
63
❖ Control systems: are grouped into two classes (based on source of control
mechanism).
i. Intrinsic/local/ control system
✓Local controls that usually involve only one organ or tissue.
For example when muscles use more O2 , and also produce more CO2 ,
intrinsic control cause dilation of the blood vessels (local vasodilatation)
ii. Extrinsic control system
✓Regulatory mechanisms initiated outside an organ.
✓Accomplished by nervous and endocrine systems.
Chapter I: Introduction & Cell Physiology
64
Components of control system
❖ Homeostatic control mechanisms have three or more components:
1. Receptor: type of sensor that monitors the environment & responds to changes,
called stimuli, by sending information (input) to the control center.
✓ Information flows from the receptor to the control center along
the afferent/sensory nerve pathways
2. Control Center:
✓CNS structures that determines the set point for a variable,
analyzes input, and coordinates an appropriate response.
✓Information flows from the control center to effectors along
the efferent/motor nerve pathways
Chapter I: Introduction & Cell Physiology
65
3. Effectors:
✓ Structure that carries out the response directed by the control center.
✓ includes: muscles & glands.
o Muscle contraction/relaxation---↑or↓ movement/motility
o Glands---- ↑or↓ glandular secretion
✓The results of the response then give feed back to influence the stimulus,
either depressing it (negative feedback) or
enhancing it (positive feedback).
Chapter I: Introduction & Cell Physiology
66
Stimulus:
change of variable
Receptor (sensor) Effector
Control
center
Variable (in homeostasis state )
feeds back to influence
magnitude of stimulus &
returns variable to
homeostasis
Output:
information sent along
efferent pathway to
Fig. Homoeostasis control mechanisms
Chapter I: Introduction & Cell Physiology
67
Types of control mechanisms (based on kinds of response)
1. Feedback - refers to responses made after change has been detected
✓ Types of feedback systems:
i. Negative FB control system.
ii. Positive FB ″ ″
✓ All systems in the body use negative or positive feedback system
to regulate their functions.
Chapter I: Introduction & Cell Physiology
68
i. Negative FB Control System
➢ In these systems, the output shuts off the original stimulus or reduces its intensity.
➢ These mechanism cause the variable to change in a direction opposite to that of
the initial change, returning it to its “ideal”, set point value.
➢ The goal of negative feedback mechanisms is to prevent sudden, severe changes
in the body.
➢ Most homeostatic control mechanisms use negative feedback mechanisms
(Thermoregulation, regulation of blood glucose, plasma volume, BP, etc.)
Chapter I: Introduction & Cell Physiology
69
✓ Generally in negative feedback control system:
Internal /External change → triggers change in controlled variable in the internal
environment → triggers reaction to oppose the change and return the variable toward
normal set point.
Importance:
✓ Maintenance of the homeostasis.
Chapter I: Introduction & Cell Physiology
70
➢ The NS along with the endocrine system, serve to regulate all system functions of
our body.
➢ For example, the hypothalamus of the brain where body's "thermostat" is found
stimulates the pituitary gland to release various hormones to control metabolism.
➢ The sympathetic and parasympathetic divisions of the ANS alternatively stimulate or
inhibit various bodily responses (such as HR, BR, etc) to maintain their proper levels.
Chapter I: Introduction & Cell Physiology
71
Examples of controlled variables regulated by
Negative Feedback
✓ Temperature regulation
✓ Blood pressure regulation
✓ Regulation of plasma volume
✓ Regulation of hormonal secretion
✓ Regulation of blood glucose
Feedback has got three disadvantages.
1. Compensation is generally incomplete.
2. Responses may be slow.
3. Too much feedback causes instability.
Chapter I: Introduction & Cell Physiology
72
Fig….Temperature Regulation
Chapter I: Introduction & Cell Physiology
73
ii. Positive FB Control System
✓ When the response enhances the original stimulus
so that the activity (output) is accelerated.
✓ Causes the variable to change in the same direction as the original stimulus, resulting
in a greater deviation from the set point.
i.e. Less common as needs some form of control or limit
✓ Controlled variable stimulates its own production
✓ Response reinforces the stimulus
✓ Response destabilizes the variable
✓ Requires an event outside the loop to stop them
Chapter I: Introduction & Cell Physiology
74
Examples of controlled variables regulated
by positive feedback control systems:
➢ Blood clotting cascade during acute hemorrhage,
➢ Contraction of the uterus during childbirth (parturition).
➢ Secretion of estrogen in pre-ovulatory phase of ovarian cycle.
➢ Na+ inflow in depolarization phase of AP …etc.
Chapter I: Introduction & Cell Physiology
75
Example1. With advancing stages of labor, oxytocin stimulates its own production to
intensify uterine contractions through a positive feedback system.
➢ Stretch receptors in walls of uterus send signals to the brain
➢ Brain induces release of hormone (Oxytocin) intoo bloodstream.
➢ Uterine smooth muscle contracts more forcefully
➢More stretch ► more hormone Release ► more contraction
Chapter I: Introduction & Cell Physiology
76
Chapter I: Introduction & Cell Physiology
77
Examples 2. Blood clotting (Acute):
➢Blood clotting is a normal response to a break in the
lining of a blood vessel.
✓ Once vessel damaged has occurred;
✓ Blood elements called platelets immediately begin
to cling to the injured site.
✓Platelets release chemical that attract more platelets.
✓This rapidly growing pileup of platelets initiates the
sequence of events that finally forms a clot.
Chapter I: Introduction & Cell Physiology
78
Chapter I: Introduction & Cell Physiology
79
Fig. The depolarization phase of nerve impulse as an example of positive FB control system.
Chapter I: Introduction & Cell Physiology
80
2. Feed forward – The term used for responses made in anticipation of a change.
➢A direct effect of stimulus on the control system before the action of feedback signal.
➢The direct effect of the stimulus is termed disturb signal or interfere signal.
Importance:
➢Makes the human body to foresee & adapt the environment exactly
(prepare the body for the changes).
Chapter I: Introduction & Cell Physiology
81
Examples:
✓Shivering before diving into the cold water.
✓Smell of food trigger digestive juice secretion.
✓Increase insulin secretion while meal is still in the digestive tract
Chapter I: Introduction & Cell Physiology
82
Homeostasis imbalance
❑ Homeostasis is so important that most disease is regarded as a
result of its disturbance, a condition called homeostatic
imbalance.
❑ Causes:
✓As we become aged,
➢ our body’s control systems become less efficient.
➢ Negative feedback mechanisms become overwhelmed &
destructive positive feedback mechanisms take over.
Chapter I: Introduction & Cell Physiology
83
Membrane Transport
✓ Plasma membrane: is a selectively permeable membrane that
separates the ICF from the ECF compartments.
➢ Some ECF molecules & ICF molecules may be able to penetrate the membrane,
while others may not.
➢ Thus, the plasma membrane is thus said to be selectively permeable
membrane.
ICF
Chapter I: Introduction & Cell Physiology
84
✓ The plasma membrane is generally not permeable to proteins & nucleic acids
(fixed organic molecules).
✓ It is, however, permeable to many other molecules, such as nutrients & metabolic
wastes which are needed to sustain metabolism.
✓The plasma membrane is also selectively permeable to certain ions; this permits
electrochemical currents across the membrane used for production of impulses in
nerve & muscle cells.
Chapter I: Introduction & Cell Physiology
85
▪ There are three categories of transport across the plasma membrane
(based on a requirement of metabolic energy).
1. Passive (Leaky) transport :
✓Transports that do not require metabolic energy.
✓ includes:
i. Simple diffusion,
ii. Facilitated diffusion &
iii. Osmosis.
2. Active (Pump) transport :
✓ Transports mechanism that utilize metabolic energy.
✓ Includes:
i. Primary A.T &
ii. Secondary A.T.
Chapter I: Introduction & Cell Physiology
86
Chapter I: Cell Physiology
1. Carrier-mediated transport
a. Facilitated diffusion
b. Active transport mechanisms
2. Non-carrier-mediated transport
a. Simple diffusion: E.g. lipid-soluble molecules through
the phospholipid layers of the plasma membrane.
a. Osmosis: (Water)
▪ The transport of molecules & ions through the plasma membrane also categorized
into two based on the requirement of carrier proteins.
87
Transport across the plasma membrane
Chapter I: Introduction & Cell Physiology
88
a. Simple Diffusion
✓ Free movement of a substance from one part of a solution to another.
✓ Net movement occurs from an area of high concentration to another area of low
concentration. e.g. Transport of blood gasses across alveoli-capillary membrane
Chapter I: Introduction & Cell Physiology
89
b. Facilitated diffusion
✓Occurs down an electrochemical gradient ("downhill"), similar to simple diffusion.
o does not require metabolic energy and therefore it is passive.
✓ is carrier-mediated (required carrier protein)
✓ is more rapid than simple diffusion.
✓ Some ions & large molecules are transported across cell membranes by specific proteins
that undergo transformational changes.
✓ Chemicals bind to specific proteins on membrane surface→
transformational changes of proteins→ movement of ions
through membrane.
Chapter I: Introduction & Cell Physiology
90
✓E.g. Glucose transport in most cells (except liver &
muscle cells) which is:
- “Downhill”,
- Carrier-mediated.
Chapter I: Introduction & Cell Physiology
91
C. Osmosis:
✓ Passive large water fluxes across a membrane
✓Conditions required:
• High conc. of solute on one side.
• Lower diffusional permeability of solute across membrane.
Chapter I: Introduction & Cell Physiology
92
Active (Pump) Transport Mechanisms
✓ ATP-ase Pumps:
❖ Primary active transport
e.g. Na+/ K+-ATP-ase ( Na+-K+ pump):
✓ Transports Na+ from intracellular to extra-cellular fluid and K+ from extra-cellular to
intracellular fluid across the CM;
✓ maintains low intracellular [Na+] and high intracellular [K+].
✓ Both Na+ and K+ are transported against their electrochemical gradients.
✓ Energy is provided from the terminal phosphate bond of ATP.
✓ Usually 3Na+/2 K+.
Chapter I: Introduction & Cell Physiology
Na+ / K+ pump
93
Chapter I: Introduction & Cell Physiology
94
❖ Secondary active transport
(Electrogenic Co-transport)
✓ The "downhill" transport of the one solutes provides energy for the "uphill"
transport of the other solute.
✓ E.g. Na+ moves down its conc. gradient (“down hill”) it co- transports solutes such
as glucose against concentration gradient (“uphill”) in muscles, liver & adipose
tissue.
✓ Metabolic energy (ATP) is not provided directly, but indirectly from the Na+
gradient that is maintained across cell membranes.
Chapter I: Introduction & Cell Physiology
95
c / Bulk transport (Vesicular Transport) systems
➢ mechanism of transport of macromolecules into and out
of the cell
➢ Also known as Vesicular transport
➢ includes:
A. Endocytosis
B. Exocytosis
Chapter I: Introduction & Cell Physiology
96
A Endocytosis
• Is a process of capturing a substance from the outside
by forming invagination of the outer part of a cell membrane.
• Requires energy
• Encompasses the following three (3) different types of transport
systems:-
I. Phagocytosis:
- Large molecules such as
bacteria, dead RBC, etc
surrounded by cell
membrane & taken up.
- also known as “cell eating ”.
Chapter I: Introduction & Cell Physiology
97
II. Pinocytosis – cell drinking
o fluid endocytosis (enclosing a small volume of ECF)
Chapter I: Introduction & Cell Physiology
98
III. Receptor-mediated-endocytosis OR clathrine mediated
endocytosis: is a process by which a cell reabsorbs materials.
e.g. Synaptic vesicle recycle in a presynaptic terminal
Chapter I: Introduction & Cell Physiology
99
B. Exocytosis
➢Is the mechanism by which cells release of their
secretary products out of the cell.
➢ is also known as “Cell vomiting”
E. g. Releases of neurotransmitters by nerve terminals.
Chapter I: Introduction & Cell Physiology
100

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  • 1. 1 By: Zewdu Minwuyelet (MSc in Medical Physiology, MPH in PH Epidemiology) Email: zwdminwuyelet@gmail.com Phone No-: +251 985898219 Ethiopian Police University Department of Nursing Human Physiology Addis Ababa, Ethiopia Nov, 2023/24
  • 2. 2 Course Description Course name: Human Physiology = ========================================== This course is designed to equip students with the basic concepts of human physiology. This course covers the physiology of humans, with emphasis on the major organs and systems and the physiological processes which govern heart beat and cardiac output, circulation, movement, plasma volume and osmoregulation, energetics and temperature regulation, respiration, digestion and reproduction.
  • 3. 3 Course contents Ch-1 Introduction & cell Physiology Ch-2 Excitable cells & membrane potentials Ch-3 Musculo-skeletal System Ch-4 Autonomous Nervous system Ch-5 Blood Physiology Ch-6 Cardio-vascular System Ch-7 Respiratory system Physiology Ch-8 Gastrointestinal system Physiology Ch-9 Renal system Physiology Ch-10 Reproductive system Physiology Ch-11 Endocrine system Physiology Ch-12 Nervous system Physiology
  • 4. 4 Teaching Methods ❖ The teaching methods will be either of the following: Lecture/discussion Assignments • Group work/seminar • Independent studies
  • 5. 5 Assessment Methods ❖ The teaching methods will be either of the following: Class room activity and attendance Written assignment and presentation Written examination (mid & final examinations)
  • 7. 7 Introduction & Cell Physiology Contents ♠ Historical background of Physiology ♠ Levels of structural organization of the human body ♠ Cells and its function ( diversity, cell theory, types, its organizations, organel function) ♠ body fluids & the internal environment ♠ The role of electrolytes in signaling ♠ Clinical correlates of body fluids & electrolytes ♠ Homeostasis ( definition, types & mechanisms) ♠ Membrane transport
  • 8. Historical Background & Definition of Physiology ❖ Aristotle (384 - 322 B.C.) was regarded as: ➢The father of natural history & the 1st person to coin the term Physiology. ➢ According to Aristotle, physiology meant the study of nature . - “Physio- nature, logy– study”, i.e. studying practically everything in the universe & in the human body. 8 Chapter I: Introduction & Cell Physiology
  • 9. ❖ Modern definition of Physiology: ✓ is the scientific study of normal body functions. ✓ It deals with the physical & chemical processes in cells and tissues to elaborate performances of the organism. ✓ Some of these physiological processes includes: - the mechanisms by which impulse transmission of nerves from one part of the body to another, - movement of the body (contraction of skeletal muscles), - the mechanisms by which the organism sees, hears, smells, digests, keeps warm, etc. - Reproduction,………..+ 9 Chapter I: Introduction & Cell Physiology
  • 10. Levels of structural organization of the human body 1 2 4 5 6 3 Smooth muscle cell Molecules Atoms Smooth muscle tissue Epithelial tissue Heart Blood vessels Smooth muscle tissue Connective tissue Blood vessel (organ) Cardiovascular system Cellular level Cells are made up of molecules. Tissue level Tissues consist of similar types of cells. Organ level Organs are made up of different types of tissues. Organ system level Organ systems consist of different organs that work together closely. Organism level The human organism is made up of many organ systems. Chemical level Atoms combine to form molecules. 10 Chapter I: Introduction & Cell Physiology
  • 11. A. Atoms & molecules • At its simplest level, the body is composed of atoms. • The most common atoms/elements in the human body are: - Carbon - Nitrogen - Hydrogen - Phosphorus - Oxygen - Sulpher • A combination of atoms molecules/compounds Macromolecules. (Organic & inorganic molecules ) 11 Chapter I: Introduction & Cell Physiology
  • 12. 12 ❖ Organic substances: ✓ Carbohydrates (like glycogen, starch, & glucose..…), Lipids (fats) Proteins, & Vitamins. ❖ Inorganic substances: ✓ Water (a universal solvent, contribute to hydrolysis rxn) ✓ Salts ✓ Dissolved inorganic ions (electrolytes…Na+, K +, Ca2+, HCO3 ✓ Minerals ✓ Blood gases… Chapter I: Introduction & Cell Physiology
  • 13. 13 Chapter I: Introduction & Cell Physiology B. Cells ❖ are basic structural & functional units of human body/life ❖ are living units ❖ Have 4 principal parts a)Plasma membrane b)Cytosol /ICF c)Organelles d)Inclusions
  • 14. 14 Chapter I: Introduction & Cell Physiology B. Tissues ❖ Are group of cells which perform a specific function ❖ are 4 different major types a) Connective tissue b) Epithelial tissue c) Muscle tissue d) Nerve tissue
  • 15. 15 Chapter I: Introduction & Cell Physiology C. Organs ❖ Are group of two or more different tissues which perform a specific function ❖ Examples: a) Heart b) Blood vessels c) Brain d) Spinal cord e) Stomach f) Small intestine…..
  • 16. 16 Chapter I: Introduction & Cell Physiology D. Systems ❖Consist of organs that provide a common/related function ❖Examples: a) Cardiovascular system b) Respiratory system c) Nervous system d) Gastrointestinal system
  • 17. 17 Chapter I: Introduction & Cell Physiology E. Organismal Level ❖ All systems of the body functioning with another comprise the total organism. ❖Examples: human being
  • 18. 2. Cells & its function • Cell is the smallest unit of life. • All life depends on the many chemical activities of cells. -Different cells perform different activity. • Each organ is an aggregate of many different cells held together by intercellular supporting structures (≈ 100 trillion cells) • Each type of cell is specially adapted to perform one or a few particular functions. ➢ Cells are highly specialized both in structure & function. For e.g., the RBCs, numbering 25 trillion in each human being, responsible to transport blood gases (oxygen & carbondioxide). 18 Chapter I: Introduction & Cell Physiology
  • 19. Fig… Structure of the cell 19 ✓Even though cells are highly specialized both in structure & function, most of them share similar features (organelle), which has similar function in different cells Chapter I: Introduction & Cell Physiology
  • 20. 20 ✓ Diversity of Cells: cells are highly specialized both in structure & function Chapter I: Introduction & Cell Physiology
  • 21. Cell Theory ✓ Cells are the structural and functional unit of life. - A cell is the smallest biological unit of living matter. ✓ All organisms are composed of cells. - Be it multicellular or unicellular ✓ Cells come only from pre-existing cells (self-replicating unit ). 21 Chapter I: Introduction & Cell Physiology
  • 22. Prokaryotic cells Eukaryotic cells ✓ Lacks a well-defined nucleus, & ✓ have a relatively simple internal organization. Have advanced & larger nucleus & has more complex internal organization. ✓ Have no membrane-bound organelles. Have many membrane-bound organelles with specialized functions ✓ have circular DNA with out protein in the cytoplasm Have linear chromosomes ✓ have smaller ribosomes have larger ribosomes ✓ have no cytoskeleton have cytoskeleton elements: - microtubules, microfilaments & intermediate filaments ✓ always found in unicellular organisms e.g. Bacteria. ✓found in multi-cellular organisms e.g. Animal & plant cells Types of Cells Chapter I: Introduction & Cell Physiology
  • 23. Organization of the cell ❖ Each eukaryotic cell has three common components: 1. Plasma membrane (cell membrane) 2. Cytoplasm containing organelles 3. Nucleus/region containing DNA 23 Chapter I: Introduction & Cell Physiology
  • 24. The cell organelles ❖ Include ✓ Cell membrane ✓ Nucleus ✓ Ribosomes ✓ Endoplasmic reticulum ✓ Golgi complex ✓ Mitochondria ✓ Lysosomes……. 24 Chapter I: Introduction & Cell Physiology
  • 25. 1. Plasma (cell) membrane ✓ A membrane that separates the interior of the cell (ICF ) from ECF environment. ✓ cell membrane is composed of double layer of phospholipids in which proteins are embedded that contribute specialized functions to the cell. ✓ it determines what can enter & leave the cell Fluid Mosaic Model: ✓ Protein molecules bobbing/floating in phospholipids sea & determine membrane’s specific functions. ✓ the cell membrane moves freely because of its oily nature (fluid) 25 Chapter I: Introduction & Cell Physiology
  • 26. ✓The plasma membrane is a fluid combination of PL, cholesrtol, & proteins. 26 Chapter I: Introduction & Cell Physiology
  • 27. Phospholipids bilayer ✓ Polar heads, outside & inside: hydrophilic head, attract water ✓ Nonpolar tails in the interior: hydrophobic tail, repel water 27 Chapter I: Introduction & Cell Physiology
  • 28. 28 Functions of the CM: 1. Regulate the passage of substances into and out of cells 2. Detect chemical messengers arriving at the cell surface or acts as receptors for signal transduction 3. Anchor cells to the extracellular matrix 4. Separates ICFs from ECFs. 5. Enzymatic activity (contain membrane bound enzyme) 6. Attachment to cytoskeleton elements. Chapter I: Introduction & Cell Physiology
  • 29. 29 ▪ Proteins in the cell membrane determine membrane’s specific functions. Because these membrane proteins act as: a. Ion channels / integral membrane proteins: ✓ water filled channels that allow for the transport of ions across the plasma membrane. 1. Non-gated/open /leaky /resting channels: ------open at rest 2. Gated channels…….closed at rest & open to application of stimulus. i. Ligand-gated ….open in response to chemicals such as drugs, neurotransmitters & hormones. ii. Voltage –gated…open in response to change of membrane potential/depolarization. iii. Mechanically-gated…open in response to physical deformation. Chapter I: Introduction & Cell Physiology
  • 30. 30 2. Gated channels…….closed at rest & open to application of stimulus. i. Ligand-gated ….open in response to chemicals ii. Voltage –gated…open in response to change of membrane potential. iii. Mechanically-gated…open in response to physical deformation. Chapter I: Introduction & Cell Physiology
  • 31. 31 b. Membrane bound enzymes: that catalyses certain chemical reactions on the surface of target tissues. e.g. Phospholipase C (PLC), Adenylyl cyclase…. etc. c. Ion pumps: that transport ions against concentration gradient with the utilization of energy/ATP. e.g. Na/K pump/ Na/K ATPase… d. Receptors: forms binding site to hormones, neurotransmitters & drugs. e. Antigens: Chapter I: Introduction & Cell Physiology
  • 32. ✓Lipid bilayer of the plasma membrane, with various membrane proteins that serve transport and signaling functions. 32 Chapter I: Introduction & Cell Physiology
  • 33. 2. The nucleus 33 ✓ Controls the cell, houses the genetic material (DNA). ✓ It is the largest organelle of the cell. ✓ Cells may have one nucleus or more than or lack a nucleus at all. e.g. ➢ Skeletal muscle cells contain more than one nucleus. ➢ Mature RBCs have no nucleus. ➢ Cardiac cells contain only one nucleus. Function: ❖ controls and directs all activities of cells. ❖ contains nucleic acids (DNA + RNA) Chapter I: Introduction & Cell Physiology
  • 34. The nucleus cont’d ✓ Composed of: ▪ Nuclear envelope ▪ Nucleolus ▪ Chromatin 34 Chapter I: Introduction & Cell Physiology
  • 35. 35 Nucleus components Structure Function Nuclear envelope ✓ Double layer membrane that surrounds the nucleus, composed of lipids & proteins molecules ➢ Supports the nucleus ➢ Controls passage of materials between the cytoplasm & the nucleoplasm Nucleolus ✓ Dense nonmembraneous mass composed of proteins & RNA molecules ➢ Produces ribosomal RNA Chromatin ✓ Fibrous strands composed of proteins & DNA. ➢ Contains genetic code that determines which proteins will manufactured by the cell Chapter I: Introduction & Cell Physiology
  • 36. 36 3. Ribosomes ✓ Are granular particles composed of proteins & RNA ✓ found both free in the cytoplasm and on the surface of the ER. Function ✓ are often called the “protein factories” of the cell ➢ Free ribosomes: ribosomes which are free within the cytoplasm. Function: synthesizes soluble proteins. - Site at which amino acids are assembled into proteins. ➢ Membrane-bound ribosomes: ribosomses embedded on the surface of endoplasmic reticulum (RER) Function: synthesizes proteins to be incorporated into membranes. Chapter I: Introduction & Cell Physiology
  • 37. 37 Chapter I: Introduction & Cell Physiology
  • 38. 38 4. Endoplasmic Reticulum (ER) ✓ It is an interconnected tubular structures which is continuous with the nuclear membrane. ✓ The ER may be either of two types: (1) Granular, or rough ER: ✓ assists in protein synthesis (2) Agranular, or smooth ER. ✓serves a variety of purposes in different cells; In striated muscle cells: it stores Ca2+ In the testes - it provides a site for enzyme reactions in steroid hormone synthesis. In the intestinal cells – absorption, synthesis, & transport of fats Chapter I: Introduction & Cell Physiology
  • 39. 39 5. Golgi apparatus ✓ Cluster of flattened membranous sacs. ✓ It is the central delivery system of the cell. ✓ It "Packages" cellular products in sacs (vesicles) & move it to designated parts of the cell. Function: ▪ modification, concentration of protein products prior to secretion. ▪ transporting of cellular products to the desired/designated parts of the cell. Chapter I: Introduction & Cell Physiology
  • 40. 40 6. Lysosomes: ✓ Are spherical membranous bags containing a number of powerful digestive enzymes. ✓ They contain > 40 types of hydrolytic enzymes. ➢These enzymes are all acid hydrolases (they function best at the acidic pH of the lysosomal compartment). Function: ▪ Digest ingested bacteria, viruses, and toxins ▪ Degrade nonfunctional organelles Chapter I: Introduction & Cell Physiology
  • 41. 41 7. Centrioles ✓ Two small cylindrical bodies composed of nine sets of three fused microtubules. ✓ located near nucleus Function: ➢Formation of spindle apparatus at poles of cell during cell division. Chapter I: Introduction & Cell Physiology
  • 42. 42 8. Mitochondria ✓ Are the organelles that function as the "powerhouse of the cell”, generating ATP, the universal form of energy used by all cells. ✓ Serve as site for the production of most of the energy of cell. ✓ It converts food nutrients such as glucose, to a fuel (ATP) that the cells of the body can use. ✓ Mitochondria are unique in that they have their own mitochondrial DNA (separate from the DNA that is in the nucleus). Function: ✓ Site of aerobic cellular respiration ✓ Contains enzymes of krebs cycle & oxidative phosphoryiation ✓ Breaks down food to make ATP Chapter I: Introduction & Cell Physiology
  • 43. 43 Structure of mitochondria Chapter I: Introduction & Cell Physiology
  • 44. 44 Body fluids & the internal environment/ ECF ✓ The ions & nutrients in the ECF are needed by the cell to maintain its life. ✓ Cells are capable of living, growing, and performing their special functions as long as the proper concentrations of oxygen, glucose, different ions, amino acids, fatty substances, and other constituent are available in this internal environment. ➢ Thus, “all cells live in essentially in the same environment”—the extracellular fluid (ECF). For this reason, the ECF is also called the internal environment of the body, or the milieu intérieur (a term introduced more than 100 years ago by the great 19thC French physiologist Claude Bernard). Chapter I: Introduction & Cell Physiology
  • 45. 45 • About 60 % of the adult human body is fluid, mainly water solution of ions & other substances. • Although most of this fluid is occur inside the cells & it is called ICF, about one third is in the spaces outside the cells and it is called ECF. • Thus, the total body fluid is distributed mainly in b/n two fluid compartment i.e. ECF and ICF. Body Fluids Chapter I: Introduction & Cell Physiology
  • 46. 46 Fluid compartments ECF= Plasma & IFs ✓ Water (1/3) ✓ High Na+, Cl- , Ca2+ and HCO3 - ✓ Nutrients: glucose, a.a, fatty acids ✓ Gases: O2, CO2 ✓ Hormones ✓ Enzymes ▪ Both fluid compartments have their fluid volume & composition essentially kept constant for the cell to plod on undisturbed. • High-water (2/3) • High K+, PO4 3 - Mg2+ • Nutrients, gases • Hormones • Enzymes ICF Chapter I: Introduction & Cell Physiology
  • 47. 47 Chapter I: Introduction & Cell Physiology
  • 48. 48 Cat ions: - Major cat ion in ECF= Na+ ✓ most of the time, responsible for depolarization phase of AP in excitable cells - Major cat ion in ICF = K+ ✓ most of the time, responsible for repolarization phase of AP in excitable cells ✓ Na-K pump in cells of mammals helps to: Push out Na that enters into cells. Push in K that leave out of cells. (To regain RMP of excitable cells) Anions: - major anion in ECF- Cl- (responsible for hyper polarization) - major anion in ICF: fixed anions (large organic molecules: i.e. Proteins, nucleotides, polyphosphates within cell. - Proteins with phosphates remaining inside cell because they are too large to diffuse out (fixed anions) Chapter I: Introduction & Cell Physiology
  • 49. 49 Chapter I: Introduction & Cell Physiology
  • 50. 50 Clinical Correlates on cellular environment ❖ Edema : accumulation of water & solutes in the IF compartment. ❖ Types 1. Pitting edema: if firm finger tip pressure on swollen area leaves a depression. 2. Non-pitting edema: edema with lack of indentation when finger tip pressure is applied to the skin. ✓ It can occur in certain disorders of the lymphatic system such as lymphedema & hypothyroidism conditions. ❖ Generalized edema (Anasarca) Reasons: ✓ Expanded IF volume. ✓ Total body sodium. Chapter I: Introduction & Cell Physiology
  • 51. 51 ❖ Cellular edema: is caused by the entry of water into the cells, inducing them to swell. ➢ This may occur because of Decreased osmolality of the fluid surrounding the cells, as in hypotonic fluid overload, or e.g. RBC in hypotonic solution→ Swelled & burst. Increased osmolality of the intracellular fluid, as in conditions that decrease the activity of the Na-K pump of the cell membrane, allowing the concentration of sodium ions within the cell to be increased. Chapter I: Introduction & Cell Physiology
  • 52. 52 ✓ Some mechanisms of Cellular edema: i. Depression of cellular metabolism → ↓Na+-K+ pump → ↑[Na+] inside the cell →Water moves to Na+→ Cellular edema. ii. Inflammation→↑membrane permeability to sodium & other ions that diffuse into cell with water→ cellular edema. Chapter I: Introduction & Cell Physiology
  • 53. 53 ❖ Water intoxication: ✓ Occurs when excessive volumes of water are absorbed too quickly leading to nausea, vomiting & shock conditions. ✓ These are caused by undue drop in plasma osmolarity before adequate inhibition of ADH secretion occurs. Chapter I: Introduction & Cell Physiology
  • 54. 54 What is homeostasis? ❖ Homeostasis, is derived from the two Greek words “homeo” =same & “stasis” =steady, refers to any process that living things use actively to maintain fairly stable conditions necessary for survival. ❖ Claude Bernard :The father of modern Physiology; According to him homeostasis defined as: • The internal environment remains relatively in a constant state though there are changes in the external environment. • Constant,stable, ≠ rigidity, can vary within narrow limit (i.e. normal physiological range) Chapter I: Introduction & Cell Physiology
  • 55. 55 ✓ All body systems working together to maintain a stable internal environment, responds to external & internal changes to function within a normal ranges. ✓ The internal environment of the body is in a dynamic state of equilibrium (continuously es with in normal physiological ranges) ✓ Homeostasis involves dynamic mechanisms that detect & respond to deviations in physiological variables from their “set point” values. ✓ Failure to function within a normal range results into disease condition. Chapter I: Introduction & Cell Physiology
  • 56. 56 Set point values Controlled variables Chapter I: Introduction & Cell Physiology
  • 57. 57 ✓ Normal ranges of some controlled variables Arterial pH 7.35 - 7.45 Glucose 75 -125 mg/100 ml Total lipid 400-800 mg/100 ml O2 content 17.2 - 22 ml/100 ml Bicarbonate 24 - 28 mEq/L Chapter I: Introduction & Cell Physiology
  • 58. 58 ✓ Homeostasis is continually being disrupted by: External stimuli: change in Environmental T° (heat & cold), PaO2, pathogens, toxins, etc.… Internal stimuli: change in pH…affects metabolic rate Blood pressure…affects other body systems activity. [ ] of water, glucose, salts, oxygen, …etc Chapter I: Introduction & Cell Physiology
  • 59. 59 • Successful compensation ➔ Homeostasis reestablished ➢ wellness • Failure to compensate ➔ Pathophysiology ➢Illness ➢Disease/Death Homeostasis is continually being disrupted by Internal & external changes Chapter I: Introduction & Cell Physiology
  • 60. 60 ✓ There are more than10 body systems, each has unique contributions to keep normal body function. ✓ However, it is the integration of all the body systems that allows the creation of a stable internal environment in which cells are able to function. For example, the maintenance of normal BP requires the integration of several organ systems including the ANS (NS), endocrine system, the CVS, renal & GI systems. Chapter I: Introduction & Cell Physiology
  • 61. 61 ✓ The major determinants of BP in the CVS are the cardiac output & the vascular resistance. ✓ The volume of blood is also a key determinant of BP controlled by a balance between fluid & salt intake, via the gastrointestinal system & their excretion via the renal system. ✓ Appetite & thirst are controlled by the nervous system, and also enhanced by the endocrine system (leptin & gherlin) integrates the activity of all body systems. ✓The golden goal of every organ is to maintain homeostasis. Chapter I: Introduction & Cell Physiology
  • 62. 62 Nervous system Endocrine system • By means of electric impulses (AP) & chemical release (neurotransmitters). By release hormones to the blood stream system, where it transported to target tissues . • The transmission of information is very rapidly & immediate effect (within milliseconds) e.g. reflex. The transmission of information is very slowly. More wide spread & longer lasting effect. e.g. growth of the body • Responds to the internal & external changes, involved for homeostasis function. Involved in more generalized effect, on activities such as growth, metabolism & reproduction etc. ❖ mainly two systems that maintain homeostasis are: Chapter I: Introduction & Cell Physiology
  • 63. 63 ❖ Control systems: are grouped into two classes (based on source of control mechanism). i. Intrinsic/local/ control system ✓Local controls that usually involve only one organ or tissue. For example when muscles use more O2 , and also produce more CO2 , intrinsic control cause dilation of the blood vessels (local vasodilatation) ii. Extrinsic control system ✓Regulatory mechanisms initiated outside an organ. ✓Accomplished by nervous and endocrine systems. Chapter I: Introduction & Cell Physiology
  • 64. 64 Components of control system ❖ Homeostatic control mechanisms have three or more components: 1. Receptor: type of sensor that monitors the environment & responds to changes, called stimuli, by sending information (input) to the control center. ✓ Information flows from the receptor to the control center along the afferent/sensory nerve pathways 2. Control Center: ✓CNS structures that determines the set point for a variable, analyzes input, and coordinates an appropriate response. ✓Information flows from the control center to effectors along the efferent/motor nerve pathways Chapter I: Introduction & Cell Physiology
  • 65. 65 3. Effectors: ✓ Structure that carries out the response directed by the control center. ✓ includes: muscles & glands. o Muscle contraction/relaxation---↑or↓ movement/motility o Glands---- ↑or↓ glandular secretion ✓The results of the response then give feed back to influence the stimulus, either depressing it (negative feedback) or enhancing it (positive feedback). Chapter I: Introduction & Cell Physiology
  • 66. 66 Stimulus: change of variable Receptor (sensor) Effector Control center Variable (in homeostasis state ) feeds back to influence magnitude of stimulus & returns variable to homeostasis Output: information sent along efferent pathway to Fig. Homoeostasis control mechanisms Chapter I: Introduction & Cell Physiology
  • 67. 67 Types of control mechanisms (based on kinds of response) 1. Feedback - refers to responses made after change has been detected ✓ Types of feedback systems: i. Negative FB control system. ii. Positive FB ″ ″ ✓ All systems in the body use negative or positive feedback system to regulate their functions. Chapter I: Introduction & Cell Physiology
  • 68. 68 i. Negative FB Control System ➢ In these systems, the output shuts off the original stimulus or reduces its intensity. ➢ These mechanism cause the variable to change in a direction opposite to that of the initial change, returning it to its “ideal”, set point value. ➢ The goal of negative feedback mechanisms is to prevent sudden, severe changes in the body. ➢ Most homeostatic control mechanisms use negative feedback mechanisms (Thermoregulation, regulation of blood glucose, plasma volume, BP, etc.) Chapter I: Introduction & Cell Physiology
  • 69. 69 ✓ Generally in negative feedback control system: Internal /External change → triggers change in controlled variable in the internal environment → triggers reaction to oppose the change and return the variable toward normal set point. Importance: ✓ Maintenance of the homeostasis. Chapter I: Introduction & Cell Physiology
  • 70. 70 ➢ The NS along with the endocrine system, serve to regulate all system functions of our body. ➢ For example, the hypothalamus of the brain where body's "thermostat" is found stimulates the pituitary gland to release various hormones to control metabolism. ➢ The sympathetic and parasympathetic divisions of the ANS alternatively stimulate or inhibit various bodily responses (such as HR, BR, etc) to maintain their proper levels. Chapter I: Introduction & Cell Physiology
  • 71. 71 Examples of controlled variables regulated by Negative Feedback ✓ Temperature regulation ✓ Blood pressure regulation ✓ Regulation of plasma volume ✓ Regulation of hormonal secretion ✓ Regulation of blood glucose Feedback has got three disadvantages. 1. Compensation is generally incomplete. 2. Responses may be slow. 3. Too much feedback causes instability. Chapter I: Introduction & Cell Physiology
  • 72. 72 Fig….Temperature Regulation Chapter I: Introduction & Cell Physiology
  • 73. 73 ii. Positive FB Control System ✓ When the response enhances the original stimulus so that the activity (output) is accelerated. ✓ Causes the variable to change in the same direction as the original stimulus, resulting in a greater deviation from the set point. i.e. Less common as needs some form of control or limit ✓ Controlled variable stimulates its own production ✓ Response reinforces the stimulus ✓ Response destabilizes the variable ✓ Requires an event outside the loop to stop them Chapter I: Introduction & Cell Physiology
  • 74. 74 Examples of controlled variables regulated by positive feedback control systems: ➢ Blood clotting cascade during acute hemorrhage, ➢ Contraction of the uterus during childbirth (parturition). ➢ Secretion of estrogen in pre-ovulatory phase of ovarian cycle. ➢ Na+ inflow in depolarization phase of AP …etc. Chapter I: Introduction & Cell Physiology
  • 75. 75 Example1. With advancing stages of labor, oxytocin stimulates its own production to intensify uterine contractions through a positive feedback system. ➢ Stretch receptors in walls of uterus send signals to the brain ➢ Brain induces release of hormone (Oxytocin) intoo bloodstream. ➢ Uterine smooth muscle contracts more forcefully ➢More stretch ► more hormone Release ► more contraction Chapter I: Introduction & Cell Physiology
  • 76. 76 Chapter I: Introduction & Cell Physiology
  • 77. 77 Examples 2. Blood clotting (Acute): ➢Blood clotting is a normal response to a break in the lining of a blood vessel. ✓ Once vessel damaged has occurred; ✓ Blood elements called platelets immediately begin to cling to the injured site. ✓Platelets release chemical that attract more platelets. ✓This rapidly growing pileup of platelets initiates the sequence of events that finally forms a clot. Chapter I: Introduction & Cell Physiology
  • 78. 78 Chapter I: Introduction & Cell Physiology
  • 79. 79 Fig. The depolarization phase of nerve impulse as an example of positive FB control system. Chapter I: Introduction & Cell Physiology
  • 80. 80 2. Feed forward – The term used for responses made in anticipation of a change. ➢A direct effect of stimulus on the control system before the action of feedback signal. ➢The direct effect of the stimulus is termed disturb signal or interfere signal. Importance: ➢Makes the human body to foresee & adapt the environment exactly (prepare the body for the changes). Chapter I: Introduction & Cell Physiology
  • 81. 81 Examples: ✓Shivering before diving into the cold water. ✓Smell of food trigger digestive juice secretion. ✓Increase insulin secretion while meal is still in the digestive tract Chapter I: Introduction & Cell Physiology
  • 82. 82 Homeostasis imbalance ❑ Homeostasis is so important that most disease is regarded as a result of its disturbance, a condition called homeostatic imbalance. ❑ Causes: ✓As we become aged, ➢ our body’s control systems become less efficient. ➢ Negative feedback mechanisms become overwhelmed & destructive positive feedback mechanisms take over. Chapter I: Introduction & Cell Physiology
  • 83. 83 Membrane Transport ✓ Plasma membrane: is a selectively permeable membrane that separates the ICF from the ECF compartments. ➢ Some ECF molecules & ICF molecules may be able to penetrate the membrane, while others may not. ➢ Thus, the plasma membrane is thus said to be selectively permeable membrane. ICF Chapter I: Introduction & Cell Physiology
  • 84. 84 ✓ The plasma membrane is generally not permeable to proteins & nucleic acids (fixed organic molecules). ✓ It is, however, permeable to many other molecules, such as nutrients & metabolic wastes which are needed to sustain metabolism. ✓The plasma membrane is also selectively permeable to certain ions; this permits electrochemical currents across the membrane used for production of impulses in nerve & muscle cells. Chapter I: Introduction & Cell Physiology
  • 85. 85 ▪ There are three categories of transport across the plasma membrane (based on a requirement of metabolic energy). 1. Passive (Leaky) transport : ✓Transports that do not require metabolic energy. ✓ includes: i. Simple diffusion, ii. Facilitated diffusion & iii. Osmosis. 2. Active (Pump) transport : ✓ Transports mechanism that utilize metabolic energy. ✓ Includes: i. Primary A.T & ii. Secondary A.T. Chapter I: Introduction & Cell Physiology
  • 86. 86 Chapter I: Cell Physiology 1. Carrier-mediated transport a. Facilitated diffusion b. Active transport mechanisms 2. Non-carrier-mediated transport a. Simple diffusion: E.g. lipid-soluble molecules through the phospholipid layers of the plasma membrane. a. Osmosis: (Water) ▪ The transport of molecules & ions through the plasma membrane also categorized into two based on the requirement of carrier proteins.
  • 87. 87 Transport across the plasma membrane Chapter I: Introduction & Cell Physiology
  • 88. 88 a. Simple Diffusion ✓ Free movement of a substance from one part of a solution to another. ✓ Net movement occurs from an area of high concentration to another area of low concentration. e.g. Transport of blood gasses across alveoli-capillary membrane Chapter I: Introduction & Cell Physiology
  • 89. 89 b. Facilitated diffusion ✓Occurs down an electrochemical gradient ("downhill"), similar to simple diffusion. o does not require metabolic energy and therefore it is passive. ✓ is carrier-mediated (required carrier protein) ✓ is more rapid than simple diffusion. ✓ Some ions & large molecules are transported across cell membranes by specific proteins that undergo transformational changes. ✓ Chemicals bind to specific proteins on membrane surface→ transformational changes of proteins→ movement of ions through membrane. Chapter I: Introduction & Cell Physiology
  • 90. 90 ✓E.g. Glucose transport in most cells (except liver & muscle cells) which is: - “Downhill”, - Carrier-mediated. Chapter I: Introduction & Cell Physiology
  • 91. 91 C. Osmosis: ✓ Passive large water fluxes across a membrane ✓Conditions required: • High conc. of solute on one side. • Lower diffusional permeability of solute across membrane. Chapter I: Introduction & Cell Physiology
  • 92. 92 Active (Pump) Transport Mechanisms ✓ ATP-ase Pumps: ❖ Primary active transport e.g. Na+/ K+-ATP-ase ( Na+-K+ pump): ✓ Transports Na+ from intracellular to extra-cellular fluid and K+ from extra-cellular to intracellular fluid across the CM; ✓ maintains low intracellular [Na+] and high intracellular [K+]. ✓ Both Na+ and K+ are transported against their electrochemical gradients. ✓ Energy is provided from the terminal phosphate bond of ATP. ✓ Usually 3Na+/2 K+. Chapter I: Introduction & Cell Physiology
  • 93. Na+ / K+ pump 93 Chapter I: Introduction & Cell Physiology
  • 94. 94 ❖ Secondary active transport (Electrogenic Co-transport) ✓ The "downhill" transport of the one solutes provides energy for the "uphill" transport of the other solute. ✓ E.g. Na+ moves down its conc. gradient (“down hill”) it co- transports solutes such as glucose against concentration gradient (“uphill”) in muscles, liver & adipose tissue. ✓ Metabolic energy (ATP) is not provided directly, but indirectly from the Na+ gradient that is maintained across cell membranes. Chapter I: Introduction & Cell Physiology
  • 95. 95 c / Bulk transport (Vesicular Transport) systems ➢ mechanism of transport of macromolecules into and out of the cell ➢ Also known as Vesicular transport ➢ includes: A. Endocytosis B. Exocytosis Chapter I: Introduction & Cell Physiology
  • 96. 96 A Endocytosis • Is a process of capturing a substance from the outside by forming invagination of the outer part of a cell membrane. • Requires energy • Encompasses the following three (3) different types of transport systems:- I. Phagocytosis: - Large molecules such as bacteria, dead RBC, etc surrounded by cell membrane & taken up. - also known as “cell eating ”. Chapter I: Introduction & Cell Physiology
  • 97. 97 II. Pinocytosis – cell drinking o fluid endocytosis (enclosing a small volume of ECF) Chapter I: Introduction & Cell Physiology
  • 98. 98 III. Receptor-mediated-endocytosis OR clathrine mediated endocytosis: is a process by which a cell reabsorbs materials. e.g. Synaptic vesicle recycle in a presynaptic terminal Chapter I: Introduction & Cell Physiology
  • 99. 99 B. Exocytosis ➢Is the mechanism by which cells release of their secretary products out of the cell. ➢ is also known as “Cell vomiting” E. g. Releases of neurotransmitters by nerve terminals. Chapter I: Introduction & Cell Physiology
  • 100. 100