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Introduction
Introduction
Introduction
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Learning Objectives
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Introduction cont’d...
Physiology focuses on mechanisms of action (processes).
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Introduction cont’d...
Physiology has a strong link with disciplines like:
• Anatomy, Biochemistry, Pathology, Pharmacology
Fields of Physiology:
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Structural levels of organization of human body
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Structural levels … cont’d
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Structural levels … cont’d
the body systems all together form a functional whole body (the
organism)
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Fig.7. Levels of organization in the human body
Homeostasis
• Homeostasis is the maintenance of a relatively constant
internal environment(ECF) despite changes in the external
environment.
• Homeostasis refers to the dynamic mechanisms that detect and
respond to deviations in physiological variables from their “set
point” values by initiating effector responses that restore the
variables to the optimal physiological range.
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Internal Environment
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Homeostasis cont’d…
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Homeostatic Control Mechanisms
3 Input: Control
center 4 Output:
Information Information sent
sent along along efferent
afferent pathway to effector
pathway to
control
center
Receptor (sensor) Effector
2 hange
C
detected
by receptor
5 Response of
effector feeds
back to influence
1 Stimulus: magnitude of
Produces stimulus and
change returns
in variable variable to
homeostasis
Variable (in homeostasis)
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Homeostasis cont’d…
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Regulatory systems of homeostasis
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Homeostasis cont’d…
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Homeostasis regulation cont’d…
1. Neural regulatory mechanism
• The nervous system regulates body functions through
generation of action potential and release of
neurotransmitters.
• Neurotransmitters are chemicals released form nerve
endings.
• To bring about complete communication among various
structures of the body, there should exist what is known as
reflex arc.
• A reflex is any response that occurs automatically without
conscious effort
• Reflex arc: is a neural pathway involved in performing reflex
activity
Example: pulling the hand away from a burning hot object
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The reflex arc is composed of five components:
Sensory System
Motor System
Effectors
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(Muscle, gland) =Desirable
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biological responses
21
Homeostasis cont’d…
2. Hormonal regulatory mechanism
– Hormones are chemical messengers secreted by endocrine
glands, and transported via blood to the target organs.
– Examples:
• Parathyroid glands secrete parathyroid hormone
to the kidneys, bone and small intestine = [Ca2+]
• Aldosterone from adrenal cortex to the kidneys,
intestine [Na+]
• Anti-diuretic hormone (ADH) causes water retention
from the kidneys and intestine.
– An organism is said to be in homeostasis when its internal
environment contains an optimum amount of nutrients,
gases, electrolytes, water, hormones, enzymes and To
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Ca2+ homeostasis
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Normal Ranges of Some Important Parameters
1. Body fluid volume = 40 L
ECF = 15L
ICF = 25L
2. Osmolality = 300 mosm/L, (280 – 300 mosm/L)
3. Body T. = 36.5 – 37.5OC
4. pH = 7.35 – 7.45
5. Blood Gases
PCO2 = 35 – 45 mm Hg
PO2 = 40 – 100 mm Hg
6. Electrolytes (ECF)
Ca2+ = 10 mg/dL
K+ = 4 meq/L
Na+ = 142 meq/L
Cl- = 103 meq/L
HCO3- = 27 meq/L
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Normal Ranges of Some Important Parameters
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 – 139 mm Hg)
Diastolic pressure = 80 mm Hg (60 – 89 mm Hg)
Pulse pressure = 40 mm Hg
Mean BP = 96 mm Hg
Pulmonary AP = 25/10
Cardiac output = 5 L/min
Blood Flow = 5 L /min
10. RBC count = 4-6 millions/mm3
WBC count = 4000-11,000/mm3
Hemoglobin (Hb) = 15g/dl
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Feedback Control Mechanisms of the
Homeostasis
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1. Negative Feedback Mechanism (NFM)
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NFM control cont’d…
• In general, if some factors (parameters) become excessive or too
little, a control system initiates the NFM, which consists of a
series of changes that return the factors toward certain mean
values (set point or normal values), thus, maintaining
homeostasis.
• Most homeostatic values of the body are controlled by NFM.
• Variables controlled by negative feedback mechanism includes:
– Control of Body temperature (BT)
– Control of Arterial blood pressure (ABP)
– Control of Blood glucose level (BGL)
– Blood gases level and many others
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Negative Feedback
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Examples of the PFM
1. 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
2. Blood clotting is an example of a very valuable use of PFM.
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3. LH surge: the positive feedback mechanism
GnRH HT
Pituitary
activates
LH
Ovary
Estrogen
>200 µg/ml
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PFM cont’d…
4. Labor during child birth
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PFM cont’d…
• Some of the action of PFM disturbs the internal environment
and cause disease and death.
• For example, if a person suffers from a heart attack that
damages the heart function, then the heart pumps less
amount of blood to the tissues including the heart muscle and
brain.
• ↓ heart pump ability ↓blood supply to all tissues including
heart this further ↓heart contraction and the heart
becomes weaker and weaker that may lead to death
– Because the heart muscle does not get sufficient nutrients
and O2, the activity of the heart becomes weaker and
weaker and the weaker the heart the lesser blood is
pumped and then death may occur.
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Cell Physiology
» Cells – are the functional & structural units of the body
» Two types of cells:
A. cells without typical nucleus = prokaryotes
B. cells with nucleus = eukaryotes
• The following table shows the difference b/n the two cells:
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Prokaryotes: (Eg. bacteria) Eukaryotes:(Human)
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Generalized Cell
Components of cells:
A typical cell has three parts:
1) the cell membrane (plasma membrane), which encloses the
cell
2) the nucleus, which contains the cell’s genetic material and
3) the cytoplasm, the portion of the cell’s interior not occupied
by the nucleus
The different substances that make up the cell are collectively
called protoplasm.
Protoplasm:
Composed mainly of five basic substances: water,
electrolytes, proteins, lipids and carbohydrates.
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A GENERALIZED CELL
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Cell structure… cont’d
Cell Membrane
Cell membrane is an extremely thin layer (7.5 nm) of lipids and
proteins that forms the outer boundary of every cell and encloses
the intracellular contents.
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Cell structure … cont’d
The outer surface of the bilayer is exposed to ECF, whereas the inner
surface is in contact with the intracellular fluid (ICF).
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Cell structure … cont’d
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Cell structure … cont’d
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Cell structure … cont’d
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Cell structure … cont’d
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Cell structure … cont’d
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Cell structure … cont’d
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Cell structure … cont’d
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Transport through the Cell Membrane
Passive Transport
Active Transport
Vesicular transport
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Transport through the Cell Membrane
• The plasma membrane is a very important structure which
functions to allow certain substances to enter or leave the cell
still excluding others to cross the 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
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Transport through the cell membrane
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Transport through the cell membrane
1. Transport for the movement of ions and small solute
molecules across the plasma membrane
I. Passive transport across cell membrane includes:
Simple diffusion
Facilitated diffusion
Osmosis
II. Active transport includes:
primary active transport
secondary active transport
ECF ECF
ICF ICF
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I. Passive Transport
1. Simple Diffusion
It is the passive movement of substances down their
concentration gradient.
– Does not need cellular metabolic energy (ATP)
– It’s powered by thermal energy of the diffusing molecules
– It’s non-carrier mediated transport
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Simple Diffusion
Factors affecting the net rate of diffusion
b. Membrane permeability
c. Concentration difference
d. Pressure difference
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Simple Diffusion …cont’d
Rate of diffusion is determined by the following factors
summarized in the formula shown below.
S. A. T. C
Rate of diffusion =
D MW
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Lipid bilayer of cell membrane
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2. Facilitated diffusion
Carrier mediated transport
– Does not need cellular metabolic energy (ATP)
– It’s powered by thermal energy of the diffusing molecules
Transports substances down their concentration gradient
Small charged substances (ions and molecules) cross plasma
membrane by facilitated diffuse
Examples: transport of glucose, proteins
Small ions, such as Na+, K+, Cl-, and Ca2+, also cross the
plasma membrane by facilitated diffusion
Facilitated diffusion of these small ions occurs through ion
channel proteins
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2. Facilitated diffusion
• Ion channels are integral proteins spanning the width of the
plasma membrane and are normally composed of several
polypeptide subunits
• Two types of ion channels found in the cell membrane;
leakage (nongated) channels and gated channels
• Ion channels are often selective
Glucose
ECF
Cell membrane
ICF
Carrier protein
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Simple diffusion vs facilitated difusion
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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 have very small (0.3 nm) in diameter, so that
they can not traverse the lipid bilayer simply. Instead they
pass through specific water channels called aquaporins:
Five aquapurins (AQ1, AQ2,….AQ5) have been
identified in the body.
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Osmosis
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II. Active transport
• Substances are transported against concentration,
electrochemical gradient, up hill direction.
– needs (directly or indirectly) metabolic energy
expenditure (ATP)
– needs carrier protein in the cell membrane
• Used for the transport of Na+, K+, Ca2+, Fe2+, H+, Cl-
• Two types of active transport:
1. Primary active transport
2. Secondary active transport
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Active transport …cont’d
1. Primary active transport:
Immediate energy source is ATP
There are integral membrane proteins that directly use
metabolic energy to transport ions against a gradient of
concentration or electrical potential
These integral proteins are called ion pumps or ATPases
Primary active transport includes:
Sodium-potassium pump or Na+/K+-ATPase
Calcium pumps, Ca2+-ATPases
H+/K+-ATPase
Proton pumps, H+-ATPases
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Active transport …cont’d
Sodium-potassium pumps or Na+/K+-ATPases
• Are found in the plasma membrane of every cell in our body
• Are responsible for maintaining the low sodium and high
potassium concentrations in the cytoplasm
• By using energy from hydrolysis of one ATP molecule it pumps
3Na+ outward and 2K+ inward
– It maintains Na+ outside and K+ inside
– It maintains electropositive outside and electronegative inside.
• Na+ - K+ pump is a carrier protein that is made up of two
subunits. It has 3 binding sites for Na+ inside
• It has 2 binding sites for K+ on the outside
• It has ATPase activity inside.
ATP = ADP + ---P + energy.
• Energy brings conformational change of the pump so that Na+
pumped outward and K+ inward.
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Active transport …cont’d
The H+/K+-ATPase:
• Present in the luminal (apical) membrane of the parietal cells
in oxyntic (acid-secreting) glands of the stomach and also in
the collecting ducts of the kidney
• This pump maintains the low pH in the stomach; secrete H+
ions into the urine when blood pH falls, and to reabsorb K+
ions
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10 Active transport …cont’d
Proton pumps, H+-ATPases:
• Are found in the membranes of the lysosomes, the golgi
apparatus and renal tubules cells cell membrane, osteoclasts
cell membrane
• Pump protons from the cytosol into these organelles, keeping
the inside of the organelles more acidic (at a lower pH)
• Proton pump in the kidney helps to secrete H+ ions into the
urine when blood pH falls
• Secretion of protons by the bone cells (osteoclasts) helps to
solubilize the bone mineral and creates an acidic environment
for bone breakdown by enzymes
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Secondary Active Transport
Is powered by an ion concentration gradient across cell
membrane, typically Na+
Metabolic energy is expended by the pumps to create and
maintain the differences in ion (Na+ ) concentrations across
cell membrane
Sodium diffusion down concentration gradient is used to carry
out the transport of another important solute against
concentration gradient across cell membrane
Carrier protein is involved
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20 Active Transport…cont’d
Figure:#
3/28/2024 Secondary active transport, NaM.+ - Glucose Co-transport Mechanism
Kefale 73
Example: 20 Active Transport
The Na+-glucose cotransporter in the human intestine entrocytes which
is called sodium-dependent glucose transporter 1 (SGLT1) is
secondary active transport system
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Secondary Active Transport …cont’d
Absorption of many amino acid molecules involve secondary
active transport
Na+/Ca2+ exchange systems is another example of secondary
active transport that removes calcium from the cell and,
together with the different calcium pumps, helps maintain a
low cytosolic calcium concentration
SGLT1 is among symport protein transporters
Na+/Ca2+ exchange systems is among antiport protein
transporters
Carrier proteins
Uniport carriers: Carry single substance to one direction
Antiport carriers: Carry two substances in opposite directions
Symport carriers: Carry two substances in the same direction
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Vesicular (Bulk) transport
Macromolecules cross the plasma membrane by vesicular
transport
Vesicular transport includes endocytosis and exocytosis
Endocytosis is the process in which a region of the plasma
membrane is pinched off to form an endocytic vesicle inside the
cell
Endocytosis include phagocytosis, pinocytosis and receptor
mediated endocytosis
A. Phagocytosis is the ingestion of large particles or
microorganisms, usually occurring only in specialized cells such as
macrophages, also called cell eating
B. Pinocytosis is the process by which dissolved solutes from the
extracellular medium are trapped inside the vesicle and
internalized by the cell and also called cell drinking.
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Vesicular transport…cont’d
C. Receptor-mediated endocytosis is a highly selective process
that enables cells to import specific large molecules that it needs
from its environment.
Receptor-mediated endocytosis is triggered by the binding of
a specific target molecule such as a protein to a surface
membrane receptor specific for that molecule.
Macromolecules such as bacteria, engulfed by the cell via
phagocytosis are called phagosomes or vacuoles
Macromolecules taken inside via pinocytosis or receptor-
mediated endocytosis are called endosomes
Exocytosis:
Allows secretion of macromolecules from the cell.
The vesicles formed in the cell move to the cell surface, fuse
with the cell membrane, and release their contents outside the
cell.
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Vesicular transport…cont’d
Endocytosis
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BODY FLUIDS
• Body fluid refers to body water and its dissolved substances
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Body fluid compartment
• In lean adults, body fluids constitute about 55% and 60% of total
body mass in females and males, respectively
Intracellular
extracellular
Intracellular Fluid
Extracellular Fluid
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83
Composition of body fluids
I. Water
• Accounts for about 60 % of the total weight of an average
adult
Example
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II. Electrolytes
• Electrolytes are chemicals that dissociate into their positive and
negative ions when they dissolve in water
• Most electrolytes are inorganic salts, acids and bases found in all body
fluids
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Fig. Major cations and anions of the intracellular and extracellular fluids.
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Function of Electrolytes
1. Regulate the osmosis of water between fluid compartments by
creating osmolarity in the body fluids. Eg. Na+, Cl-
2. Ions help maintain the acid–base balance required for normal cellular
activities,
Eg. H+,Hco3 -
Eg. Ca2+
89
2.Water loss
• Kidneys excrete about 1500 ml urine/day
90
Fig. Sources of daily water gain and loss under
normal conditions 91
Regulation of Fluid Exchange and Osmotic
Equilibrium between ICF and ECF
• The relative amounts of extracellular fluid distributed between the
plasma and interstitial spaces are determined mainly by the balance
of hydrostatic and colloid osmotic forces across the capillary
membranes
• The distribution of fluid between intracellular and extracellular
compartments, in contrast, is determined mainly by the osmotic
effect of the smaller solutes
sodium, chloride, and other electrolytes
• The reason for this is that the cell membranes are highly permeable
to water but relatively impermeable to even small ions
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Osmosis and Osmotic pressure
Osmosis
Osmosis is the net diffusion of water across a selectively permeable
membrane from a region of high water concentration to one that
has a lower water concentration
Water diffuses from a region of low solute concentration to one
with a high solute concentration
Osmotic pressure
Osmosis of water molecules across a selectively permeable
membrane can be opposed by applying a pressure in the direction
opposite that of the osmosis
Pressure
Fig. Osmosis, osmotic pressure. Red objects = solute, Yellow shade = water,
Dotted line = semipermeable membrane
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Osmolality and Osmolarity
• The osmolal concentration of a solution is called osmolality when the
concentration is expressed as osmoles per kilogram of water
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Tonicity … cont’d
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Tonicity … cont’d