Human Physiology

Physiology Unit

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General & Cellular Basis of
Medical Physiology

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 Outline
 General Introduction to Physiology
 Historical Background

 Functional Organization of the human body

 The Fluid Environment of the Body
 Volume and Composition of Body Fluids
 Composition of Plasma and Interstitial Fluid
 Composition of ICF and ECF
 Donnan Effect
 Basic Principles of Osmosis and Osmotic Pressure
 Homeostasis
 Regulatory Systems of Homeostasis
 Feedback System
 NFM & PFM with Examples
 Feed Forward Mechanism
 Generalized Eukaryotic Cell 3
 Objectives:
 Define physiology
 Describe the functional organization that make up the human
body
 Name the different fluid compartments in the human body
 Compare and contrast the composition of ICF Vs. ECF
 Define homeostasis and explain how this concept is used in phys-
iology
 Define negative and positive feedback mechanisms
 Explain examples of NFM & PFM
 Describe the structure and functions of plasma membrane

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 I . General Introduction to Physiology
Definition of Physiology

Is the study of the functions of living organisms and how they
are regulated and integrated.
It deals with the integrated activities of different organs & organ
systems, and the conditions which determine normal functions of
body parts.
Human physiology is the study of the normal function of hu-
man body.
It is the study of biological functions of how the human body
works from molecular mechanisms within cells to complicated
human being.
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 General Introduction…
 The ultimate goal of human physiology is to understand the
normal functions of cells, tissues, organs & systems of human
body.
 It attempts to explain the specific characteristics and mecha-
nisms of the human body that make it a living being.

 Generally physiology is the study of biological function of how

the body works, from molecular mechanisms within cells to
the actions of tissues, organs, and systems, and how the organ-
ism as a whole accomplishes particular tasks essential for life.

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 General Introduction…
Fields of Physiology:
The vast field of physiology can be divided into viral phys-
iology, bacterial physiology, plant physiology, vertebrate
physiology, invertebrate physiology, mammalian physiology,
human physiology, and many more subdivisions.
Human physiology (Cell physiology, CV physiology, Re-
nal, Respiratory, GIT, Endocrine, CNS physiology etc.)

Physiology is closely related to several other branches of sci-

ence such as anatomy, pharmacology, biochemistry, pathology
etc.
Therefore, physiology is not an isolated science but highly as-
sociated with other sciences.

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Historical Background
Aristotle (384 - 322 B.C.) was
• The 1st person to coin the term physiology.
• According to Aristotle, Physiology meant the
study of nature- “Physis” - nature, “logy” -
study. This meant studying practically everything
in the Universe and in the human body.
Claudius Galen (130–200 A.D) was the person who:
Began modern experimental physiology (studying body parts of an-
imals like blood vessels and their functions);
Got the credit for changing the interpretation of the word into its
modern usage - the study of normal bodily functions embodying the
processes and activities that help discern functional similarities and
differences in living organisms.
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Historical Background…
William Harvey (1578 - 1657), English physician correctly described
the direction of circulation of blood in 1628, that the heart pumps blood
through closed system of vessels.
– Described that the heart pumps blood, arteries transport oxy-
genated blood, exchange of substances occur at the systemic cap-
illaries and veins return deoxygenated blood.
Claude Bernard (1813 -1878), a French physiologist described
that every cell in body is bathed with the fluid environment
called ECF.
• He called ECF is the internal environment of the body, Mileue
interieor.
• ECF contains all the needed substances for cells.
• He observed that the internal environment remains remarkably
constant despite changing conditions in the external environ-
ment.
•Walter Cannon (1871-1945), American great physiologist, termed the
maintenance of constant conditions in the ECF as homeostasis.

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 Functional organization of the human body
Systems of the Human Body
1. Integumentary System
 Components: Skin and structures associated with it, such as hair, nails, sweat glands
and oil glands.
 Functions: Protects the body; helps regulate body temperature; eliminates some
wastes; helps make vitamin D; and detects sensations such as touch, pain, warmth
and cold.
2. Skeletal System
 Components: Bones and joints of the body and their associated cartilages.
 Functions: Supports and protects the body; provides a surface area for muscle at -
tachments; aids body movements; houses cells that produce blood cells; stores min-
erals and lipids (fats).
3. Muscular System
 Components: Muscles composed of skeletal muscle tissue attached to bones.
 Functions: Produces body movements, such as walking; stabilizes body position (pos-
ture); generates heat.
 Systems of the Human Body…
4. Nervous System
 Components: Brain, spinal cord, nerves, and special sense organs, such as the eyes
and ears.
 Functions: Generates action potentials (nerve impulses) to regulate body activities;
detects changes in the body’s internal and external environments, interprets the
changes and responds by causing muscular contractions or glandular secretions.
5. Endocrine System
 Components: Hormone-producing glands (pineal gland, hypothalamus, pituitary
gland, thymus, thyroid gland, parathyroid glands, adrenal glands, pancreas, ovaries
and testes) and hormone-producing cells in several other organs.
 Functions: Regulates body activities by releasing hormones, which are chemical mes-
sengers transported in blood from an endocrine gland or tissue to a target organ.
6. Cardiovascular System
 Components: Blood, heart and blood vessels
 Functions: Heart pumps blood through blood vessels; blood carries oxygen and nutri-
ents to cells and carbon dioxide and wastes away from cells and helps regulate acid–
base balance, temperature and water content of body fluids; blood components help
defend against disease and repair damaged blood vessels.
 Systems of the Human Body…
7. Digestive System
 Components: Organs of gastrointestinal tract, a long tube that includes the mouth,
pharynx (throat), esophagus, stomach, small and large intestines and anus; also in-
cludes accessory organs that assist in digestive processes, such as the salivary
glands, liver, gallbladder and pancreas.
 Functions: Achieves physical and chemical breakdown of food; absorbs nutrients;
eliminates solid wastes.
8. Urinary System
 Components: Kidneys, ureters, urinary bladder and urethra.
 Functions: Produces, stores, and eliminates urine; eliminates wastes and regulates
volume and chemical composition of blood; helps maintain the acid–base balance of
body fluids; maintains body’s mineral balance; helps regulate production of red
blood cells.
9. Lymphatic System and Immunity
 Components: Lymphatic fluid (lymph) and vessels; also includes spleen, thymus,
lymph nodes and tonsils.
 Functions: Returns proteins and fluid to blood; carries lipids from gastrointestinal
tract to blood; includes structures where lymphocytes that protect against disease-
causing microbes mature and proliferate.
 Systems of the Human Body…
10. Respiratory System
 Components: Lungs and air passage ways such as the pharynx (throat), lar-
ynx (voice box), trachea (windpipe) and bronchial tubes leading into and out
of the lungs.
 Functions: Transfers oxygen from inhaled air to blood and carbon dioxide
from blood to exhaled air; helps regulate acid–base balance of body fluids;
air flowing out of lungs through vocal cords produces sounds.
11. Reproductive System
 Components: Gonads (testes in males and ovaries in females) and associ-
ated organs (uterine tubes, uterus and vagina in females and epididymis,
ductus deferens and penis in males).
 Functions: Gonads produce gametes (sperm or oocytes) that unite to form a
new organism; gonads also release hormones that regulate reproduction
and other body processes; associated organs transport and store gametes.
Systems of the Human Body…
15
 II. The Fluid Environment of the Body
 Body fluid; refers to a watery solution of dissolved substances

such as oxygen, nutrients, and wastes.

 It is also called “The total body water (TBW)”

 TBW makes up approximately 60% of the body weight and it

varies with age, gender and degree of obesity (amount of adipose

tissue in the body).
 Total body water is distributed between two major body fluid

compartments:

1. Intracellular fluid compartment (ICF)

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2. Extracellular fluid compartment (ECF)
 Body fluid compartments…

• The ECF consists of all the body fluids outside of cells

 The two major compartments of total body water are divided

by the cell membrane.

 The intracellular fluid compartment is the larger compartment

and contains approximately two thirds of total body water.

 The remaining one third is contained in the extracellular fluid

compartment.

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 Body fluid compartments…

 Intracellular fluid is fluid inside cell membrane of 100 trillion

cells in the human body.

 The fluid of each cell contains its individual mixture of differ-

ent constituents, but the concentrations of these substances are
similar from one cell to another.

 In fact, the composition of cell fluids is remarkably similar

even in different animals.

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 Body fluid compartments…

 The volumes of total body water, ICF, and ECF in average 70kg
adult man.

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 Body fluid compartments…

 The ECF compartment is further subdivided into interstitial fluid

and plasma, which are separated by the capillary wall.

 The interstitial fluid surrounds the cells in the various tissues of

the body and accounts for three fourths of the ECF volume.

 Interstitial fluid is the fluid that fills the narrow spaces between
cells of tissues and it actually bathes the cells outside the blood
vessels.

 Plasma is the fluid circulating in the blood vessels and represents

the remaining one fourth of ECF.
 All the other sub compartments of the extracellular compartment
(transcellular fluid) constitute relatively small volumes.
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 Body fluid compartments…

 ECF also includes other transcellular fluids (peritoneal fluid,

pericardial fluid, cerebrospinal fluid, intraocular fluid and
synovial fluid).

 Transcellular fluid is usually considered to be a specialized

type of ECF, although in some cases its composition may dif-
fer markedly from that of the plasma or interstitial fluid.

 The transcellular fluid compartment comprises approximately

2 to 4% of the TBW and contains approximately 1 to 2 L of
water.
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Fluid compartments of the body

Fluid compartments volume for an average 70 kg lean male

Volume of Body Fluids
 In the human body, water constitutes a high proportion of body
weight.

 The total amount of fluid or water is called total body water,

which accounts for 50% to 70% of body weight.

 For example, a 70-kilogram (kg) man whose total body water is

60% of his body weight has 42 kg or 42 liters (L) of water (1 kg
water ≈ 1 L water).

 TBW depends on age, gender and percentage of body fat.

 Total body water correlates inversely with body fat and age.

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Volume of Body Fluids…

 Thus, total body water is a higher percentage of body

weight when body fat is low and a lower percentage
when body fat is high.

 Females have a higher percentage of adipose tissue

than males, they tend to have less body water.

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Composition of Plasma and Interstitial Fluid
 As the blood flows through the smallest of blood vessels in all parts of the
body, the plasma exchanges oxygen, nutrients, wastes, and other substances
with the interstitial fluid.

 The capillary wall is virtually impermeable to large molecules such as plasma

proteins.

 Because of these exchanges, concentrations of dissolved substances are virtu-

ally identical in the plasma and interstitial fluid, except for protein concentra-
tion (which remains higher in plasma than in interstitial fluid).

 With this major exception, the entire extracellular fluid may be considered to
have a homogeneous solute composition.

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 Composition of Plasma and Interstitial Fluid

 The maintenance of a relatively constant volume and a stable

composition of the body fluids is essential for homeostasis.

 Plasma and interstitial fluid are separated only by highly per-

meable capillary membranes, their ionic composition is simi-
lar.

 The difference between these two compartments is the higher

concentration of protein in the plasma and only small amounts
of proteins are leaked into the interstitial spaces in most tis-
sues.
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Composition of Plasma and Interstitial Fluid

 The concentration of positively charged ions (cations) is

slightly greater (2%) in the plasma than in the interstitial fluid.

 Conversely, negatively charged ions (anions) tend to have a

slightly higher concentration in the interstitial fluid compared
with the plasma.

 This is due to plasma proteins which have a net negative

charge and, tend to bind cations and repel anions.

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 Composition of ICF and ECF

 The compositions of ICF and ECF are strikingly different

 The major cation in ECF is sodium (Na+), and the balancing an-
ions are chloride (Cl-) and bicarbonate (HCO3-).

 The major cations in ICF are potassium (K+) and magnesium

(Mg2+), and the balancing anions is organic phosphate (PO43-).

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 Other notable differences in composition involve Ca2+ and pH.
 Typically, ICF has a very low concentration of ionized Ca2+ (≈10-7
mol/L), whereas the Ca2+ concentration in ECF is higher.
 ICF is more acidic (has a lower pH(7.1-7.2)) than ECF(7.4).
 Note that: substances found in high concentration in ECF are
found in low concentration in ICF, and vice versa.

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Normally, cells neither shrink nor swell because intracellular
and interstitial fluids have the same osmolarity.
Changes in the osmolarity of interstitial fluid, however, cause fluid
imbalances.
An increase in the osmolarity of interstitial fluid draws water out
of cells, and they shrink slightly.
A decrease in the osmolarity of interstitial fluid, by contrast, causes
cells to swell.

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Fluid compartments

ICF ECF
 Water
•Water  High Na+, Cl- , Ca2+ and HCO -
3
•High K+, Po43-,  Nutrients: glucose, aa, lipids
Mg2+  Gases: O , CO
•Nutrients, gases 2 2

•Hormones  Hormones
•Enzymes  Enzymes

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 Donnan Effect
 The plasma proteins have a net negative charge and therefore tend to
bind cations such as sodium and potassium ions, thus holding extra
amounts of these cations in the plasma along with the plasma pro-
teins.

 Conversely, negatively charged ions (anions) tend to have a slightly

higher concentration in the interstitial fluid compared with the
plasma, because the negative charges of the plasma proteins repel the
negatively charged anions.

 Because of the Donnan effect, the concentration of positively charged

ions (cations) is slightly greater (~2 %) in the plasma than in the in-
terstitial fluid.
Donnan Effect…
 Composition of body fluids…

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Basic Principles of Osmosis and Osmotic Pressure

Osmosis
 Is a type of diffusion in which there is net movement of a sol-
vent (water in living systems) through a selectively permeable
membrane.

 Is movement of water across selectively permeable plasma

membranes from an area of higher water concentration to an
area of lower water concentration or from an area of lower
solute concentration to an area of higher solute concentration.

 Osmosis occurs only when a membrane is permeable to water

but is not permeable to certain solutes.
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Basic principles of osmosis and osmotic pressure…
Osmotic pressure
 Is the pressure needed to stop the movement of water by osmosis.
 Exerted by particles in a solution, whether they are molecules or ions, is
determined by the number of particles per unit volume of fluid, not by the
mass of the particles.

 Determined by the concentration of the solution in terms of number of par-

ticles; not in terms of mass of the solute.

 The higher the solute concentration, the higher the solution’s osmotic pres-
sure.

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Basic principles of osmosis and osmotic pressure…

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Basic principles of osmosis and osmotic pressure…
 The term osmole refers to the number of osmotically active
particles in a solution.
 Osmolality refers when the concentration is expressed as os-
moles per kilogram of water.
 Osmolarity refers when it is expressed as osmoles per liter of
solution.
 Osmolarity is commonly used, because it is easier to express
body fluid quantities in liters of fluid rather than in kilograms
of water.
 Note that about 80% of the total osmolarity of the interstitial
fluid and plasma is due to Na+ and Cl-, whereas for intracellu-
lar fluid, almost half the osmolarity is due to K+.

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Basic principles of osmosis and osmotic pressure…

Compare blood hydrostatic pressure vs blood colloid

osmotic pressure (oncotic pressure)?
 Fluids in the “potential spaces" of the body

 Some examples of "potential spaces" are pleural cavity, peri-

cardial cavity, peritoneal cavity, and synovial cavities.

 Virtually all these potential spaces have surfaces that almost

touch each other, with only a thin layer of fluid in between,
and the surfaces slide over each other.

 To facilitate the sliding, a viscous proteinaceous fluid lubri-

cates the surfaces.

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 Fluids in the “potential spaces" of the body

 Fluid is continuously exchanging between the capillaries and

the potential spaces.
 Fluids, electrolytes, or even proteins, all move back and forth
between the space and the interstitial fluid.
 Therefore, each potential space is in reality a large tissue
space.
 Lymphatic vessels drain protein from the potential spaces into
circulation.
 Each potential space is either directly or indirectly connected
with lymph vessels.

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III. Homeostasis
 The term homeostasis is mean that maintenance of static or constant condi-
tions in the internal environment (ECF).
 It is the ability to maintain a relatively stable internal env’t in an ever-
changing outside world.
 The internal env.t of the body is in a dynamic state of equilibrium.
 Essentially all organs of the body perform their functions to maintain con-
stant conditions in the ECF.
For example
 Lungs maintain the normal concentration of respiratory gases in blood.
 The CVS transports required substances and removes waste products.
 The kidneys maintain constant ionic concentration.
 The GIT provides nutrients.

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Regulatory Systems of Homeostasis
 The nervous system and the endocrine system are the two controlling bodies
of homeostasis
1. The nervous regulatory mechanism
 The nervous system regulates homeostasis by sending electrical signals known
as nerve impulses (action potentials) to organs that can counteract changes
from the balanced state.
 The nerves system is composed of three major components the sensory por-
tion, the integrative portion and the motor portion.
 The sensory receptor detects any change in the body (BGL, BT, BP, etc) and
send impulse to the spinal cord & brain (CNS).
 The CNS associate the information store, generate thought and send appropri-
ate response to the effector organs (muscle + glands) through the motor sys-
tem.

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Regulatory systems of homeostasis…
2. The hormonal regulatory mechanism
 The endocrine system includes many glands that secrete messenger mole-
cules called hormones into the blood.
 Hormones are chemical messengers secreted by endocrine glands, and
transported in blood to the target gland (organs).
 Nerve impulses typically cause rapid changes, but hormones usually work
more slowly.
Examples:
 PTH  to the kidney, bone, intestine = [Ca2+]
 Aldosterone  to the kidney   [Na+]
 ADH controls water electrolyte balance
 An organism is said to be in homeostasis when its internal environment
contains an optimum amount of nutrients, gases, electrolytes, water, hor-
mones, enzymes and temperature.

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Calcium Homeostasis

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Calcium-Homeostasis

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Comparison of Control by the Nervous and Endocrine Systems
Characteristics Nervous System Endocrine System

Mediator Molecules Neurotransmitters released Hormones delivered to tissue

locally in response to nerve throughout the body by the blood
impulse

Site of mediator action Close to site of release (at Far from site of release (usually),
synapse), binds to receptors binds to receptors on or in target
in postsynaptic membrane cells

Types of target cells Muscle (Skeletal, cardiac and Cells throughout the body
smooth) cells, gland cells and
other neurons

Duration of action Generally briefer (within mil- Generally longer (seconds to days)
liseconds)

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 Homeostatic values
1. Body fluid volume = 42 L
ECF = 14L
ICF = 28L
2. Osmolarity= 300 mosm/L(285 – 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 – 104 mm Hg

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Homeostatic values
6. 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
7. Blood Glucose level (fasting): 70 – 110 mg/dL
8. 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 = 93 mm Hg
Cardiac output = 5 L/min
9. RBC count = 4-6 millions/mm3
10. WBC count = 4,000-11,000/mm3
11. Platelets count = 250,000-500,000/mm3
12. Hb = 12-18 g/dl in F, 14-20 g/dl in M
Deviations in normal ranges = pathology 50
51
 Disturbances of homeostasis
 Deviations from normal ranges = Pathology

Hypo/ Hyperthermia ….. ↓or↑ Temperature

Hypo/ Hypercapnia ….. ↓or↑ PCO2

Acidosis/Alkalosis ….. ↓or↑ PH

Hypoxia/ Hyperoxia …. ↓or↑ PO2

Hypo/ Hypercalcemia …. ↓or↑ Ca2+

Hypo/ Hyperglycemia … ↓or↑ Glucose

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 Feedback System
 Homeostasis is maintained through the regulatory process called
“feedback system or feedback loop”.
 A feedback loop is a cycle of events in which a body condition
(such as temperature) is continually monitored and adjusted to be
within specific limits.
 A Feedback loop has the following main components:
1. Stimulus: Produces change in variable.
2. Receptor: Detects change in variable.
3. Afferent pathway/Input: Carries information to control center
4. Control center: sets the normal range, receives input from the
receptor and sends output when changes are needed.
5. Efferent pathway/Output: Carries information to effectors.
6. Effectors: that produces a response or effect that changes the
physiology.

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 Stimulus
 The body can regulate its internal environment through many
feedback systems.
 Each monitored variable, such as body temperature, blood
pressure, or blood glucose level, is termed a controlled condi-
tion.
 Any disruption that changes a controlled condition is called a
stimulus.
 Normal equilibrium among body processes may be disturbed.
 If the homeostatic imbalance is moderate, a disorder or disease
may occur; if it is severe, death may result.
 Stimulus
 At the level of the milieu interieur, tightly regulated parameters
include body core temperature and plasma levels of oxygen,
glucose, K+, Ca2+, and H+.

 Cells regulate many of the same parameters that the body as a

whole regulates: volume, the concentrations of many small in-
organic ions (e.g., Na+, Ca2+, H+), and energy levels (e.g., ATP).

 NB: Homeostasis also occurs at the level of the single cell.

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 Stimulus
 Most homeostatic regulatory mechanisms make adjustments
only when they detect a difference between the actual value of
the regulated variable and the normal “desired” value, called
the set point.

 Any difference between the actual value and the set point con-
stitutes an error signal.

 Note that the set point cannot be held absolutely constant.

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 Receptors (sensors)
 Cells (often neurons) that are sensitive to changes in the con-
trolled condition (the regulated variable) and send information
to an integrating center.

 Typically, the input is in the form of nerve impulses or chemi-

cal signals.

 For example, certain nerve endings in the skin sense change in

body temperature.
 Afferent pathway carries information from receptors to con-
trol center.
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 Integrating center
 Often a particular set of neural circuits in the brain or an en-
docrine gland, which compares the regulated variable to the
set point and orchestrates the appropriate response.

 Output from the control center typically occurs as nerve im-

pulses, or hormones or other chemical signals.

 Efferent pathway carries information from integrating center

to effectors.

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 Effectors
 Are body structure that receives output from the control center
and produces a response or effect that changes the controlled
condition.

 Nearly every organ or tissue in the body can behave as an ef-

fector.

 The integrating center may cause increases or decreases in ef-

fectors’ action to counter the deviations from the set point.

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 Components of feedback system

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Homeostatic controlling mechanism

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 Homeostatically regulated variables
Body temperature
Blood composition (ions, sugars, proteins, water)
Concentrations of O2 & CO2 in the blood
Blood pH & electrolytes
Blood osmolality
Blood pressure, cardiac output, heart rate
Respiratory rate & depth
Secretions of endocrine glands
Rate of chemical reactions intracellularly

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 Factor disrupting homeostasis
External stimuli
 Heat, cold
 Lack of O2
 Pathogens & toxins
 Internal stimuli
 Abnormalities in visceral organs

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Feedback control mechanisms of the homeostasis

There are two types of feed back mechanisms:

A.The Negative Feedback Mechanism (NFM)
B.The Positive Feedback Mechanism (PFM)

 Thousands of homeostatic control mechanisms have common

characteristics (negative & positive feedback) nature.

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Negative Feedback Mechanism (NFM)
 It works by producing an effect which opposes the previous condition
(the initiating stimulus) of the organ.

 For example: if the PCO2 is increased in the blood, the NFM stimulates
pulmonary ventilation rate, which has an effect on decreasing PCO2 in
blood to normal.

 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 returns the factors toward certain mean values (set point or normal
values), thus, maintaining homeostasis.

 Most homeostatic values of the body are controlled by NFM.

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 Negative Feedback Mechanism (NFM)

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Examples of Negative Feedback Mechanism

1. PaCO2 regulation
2. Blood pressure regulation
3. Regulation of blood glucose
4. Temperature regulation
1. PaCO2 Regulation

3
.
PaCO2 Regulation…

 The aortic bodies send sensory information

to the medulla in the vagus nerve (X)
 The carotid bodies stimulate sensory
fibers in the glossopharyngeal nerve (IX)
 2. Blood Pressure Regulation
 The baroreceptor system, is a simple and excellent example of a
rapidly acting control mechanism of blood pressure.

 In the walls of the bifurcation region of the carotid arteries in the

neck, and also in the arch of the aorta in the thorax, are many nerve
receptors called baroreceptors, which are stimulated by stretch of
the arterial wall.

 When the arterial pressure rises too high, the baroreceptors send
barrages of nerve impulses to the medulla of the brain. Here these
impulses inhibit the vasomotor center, which in turn decreases the
number of impulses transmitted from the vasomotor center through
the sympathetic nervous system to the heart and blood vessels.
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2. Blood Pressure Regulation…

 Lack of these impulses causes diminished pumping

activity by the heart and also dilation of the peripheral

blood vessels, allowing increased blood flow through
the vessels.
 Both of these effects decrease the arterial pressure

back toward normal.

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 Blood Pressure Regulation…
1) ABP baroreceptor compressed  firing ac-
tivity increased  vasomotor center inhibited
SNS out flow reduced   ABP

2) ABP baroreceptor relaxed  firing activity

reduced  vasomotor center excited SNS out
flow increased  ABP

 The afferent fibers are glossopharyngeal & the va-

gus from carotid sinus and aortic arc respec-
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tively
73
Figure: Vagus and glossopharyngeal nerves
 Blood pressure regulation…
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Blood Pressure Regulation…
Blood Pressure Regulation…
3. Regulation of Blood Glucose
Regulation of Blood Glucose…
 4. Temperature Regulation
Controlling Body Temperature in Hot Conditions
More sweat is produced by sweat glands
 evaporation of sweat takes away heat which produces a cooling
effect
Vasodilation of skin arterioles
 arterioles near the surface of the skin dilates
 to let more blood flows near the skin surface
 to have more heat lost by conduction & radiation
Erector muscles relax
 hairs lie flat on the skin
 reduce thickness of air trapped among the hairs (not effective in
human because human’s hairs are short)
Decrease metabolic rate & muscle contraction
 gain less heat
  Controlling Body Temperature in Cold Condi-
tions
Vasoconstriction of skin arterioles
arterioles near the surface of the skin constrict
to let less blood flows near the skin surface
to have less heat lost by conduction & radiation
Erector muscles contract
pull hairs erect for trapping more air
thicker layer of air acts as a good insulator of heat
Less sweat is produced by sweat glands
reduce heat loss by evaporation
Increase metabolic rate & muscle contraction
gain more heat
causes shivering
 The Positive Feedback Mechanism (PFM)
 It works by producing an effect which enhances or repeats the same action like
that of the starting stimulus.
 The PFM also called vicious circle. Most of the action of this mechanism dis-
turbs the internal environment and cause disease and death.
 Output not returned to the normal input, i.e. response is in the same direction as
the stimulus.
 Rare in biology because in many cases, it causes instability leading to death, i.e.
it favors instability.
 Fore 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.
 If 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.

83
Examples of the PFM
 Generation and propagation of the action potential.
Stimulated nerve fiber  opening of Na+ channels  en-
try of few Na+ stimulates the opening of more and more
Na+ channels.
 Labor during child birth, uterine contraction is enhanced as the
head of the baby stretches the cervix.
 LH-surge
 Blood clotting
 Severe shock (vicious cycle)
 Viral infection: virus invades cellreplicates in cellmany
virusesinvasion of other cellsfurther replication

84
 1. Generation and propagation of the action potential

85
 2. Labor during child birth

86
Labor during child birth

87
Labor during child birth

88
3. LH surge: the positive feedback mechanism

GnRH HT

Pituitary
activates

LH

Ovary

Estrogen
>200 µg/ml
89
 LH surge: the positive feedback mechanism…

 The surge of luteinizing hormone (LH) that occurs as a result

of the stimulatory effect of estrogen on the anterior pituitary
before ovulation.

 The secreted LH then acts on the ovaries to stimulate addi-

tional secretion of estrogen, which in turn causes more secre-
tion of LH.

90
 4. Blood clotting

91
Blood clotting
 During hemostasis, three phases occur in rapid sequence
1. Vascular spasm – immediate vasoconstriction in
response to injury
2. Platelet plug formation
3. Coagulation (blood clotting)

Blood clotting process is a PFM, clotting is a NFM for

maintenance of normal blood volume.
 Feed Forward Mechanism
 In this mechanism, disturbance is sensed and corrective mea-
sure is taken in anticipation of a change, i.e., a feed forward
mechanism anticipates changes.
 For example, rates of heart beat and breathing increase before
a person begins to exercise.

 The operation of the regulator in feed forward is “open loop”,

i.e. the regulated variable is not sensed.
 A feed forward controller, by exclusion, generates commands
without using continuous negative feedback, i.e. its moment-
to-moment operations are open loop.
93
 Cell physiology

94
IV. Generalized Eukaryotic Cell

95
Generalized cell…
Components of cells
1. A typical cell has two parts: nucleus and cytoplasm.
2. The nucleus is separated from the cytoplasm by a
nuclear membrane and
3. The cytoplasm is separated from the surrounding
fluid (ECF) by the plasma membrane

96
97
 Cytoplasm
 The cytoplasm is filled with

1. Cytosol: this contains mainly dissolved proteins, electrolytes, glu-

cose, neutral fat globules, glycogen granules and secretory vesicles.
2. Organelles: the endoplasmic reticulum, the Golgi apparatus, mito-
chondria, lysosomes, peroxisomes etc.

 The cytoplasm is separated from the surrounding fluids by a cell

membrane (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.

98
 Generalized cell…
 Cells are the basic structural
and functional units of the
human body
 All organisms are composed
of cells
 Organismal activity depends
on individual and collective
activity of cells
 Continuity of life has a cel-
lular basis

99
Cells vary in:
• Size
• Structure
• Function
• Life span

100
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.
Ribosomes:
are the sites of protein synthesis in the cell
small particles composed of rRNA and proteins
found in two forms: attached to the wall of ER or as free ribo-
somes.
 Free ribosomes are found in two forms
o scattered in the cytoplasm (monosomes) and
o clustered (aggregated) to form functional units called
polyribosomes
 Eukaryotic ribosomes are larger and more complex than prokary-
otes
101
 Endoplasmic reticulum (ER)
 Flattened sheets, sacs & tubes of membrane

 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.

 The rER is studded with ribosomes.

 rER is the site of protein synthesis

 Site where most materials and components targeted for trafficking

102
 Rough endoplasmic reticulum
 The outer surface of rER is studded with ribosomes, the sites of
protein synthesis.

 The rER is the site of translation of mRNA and posttransla-

tional modification of proteins.

 Thus rER produces secretory proteins, membrane proteins, and

many organellar proteins.

 The function of rER is to segregate proteins that are being ex-

ported from the cell.

103
 Smooth endoplasmic reticulum
 Extends from the rER.
 It does not have ribosomes on the outer surfaces of its mem-
brane.
 Function of sER varies in different cells.
 Does not synthesize proteins, but synthesizes fatty acids and
steroids, such as estrogens and testosterone.
 Inactivates or detoxifies drugs and other potentially harmful
substances.
 Stores and releases calcium ions that trigger contraction in
muscle cells.

104
Endoplasmic reticulum (ER)
Endoplasmic reticulum (ER)
 Golgi complex/Golgi apparatus/Golgi body

 The Golgi apparatus is a stack

of flattened, membrane-bound
sacks with many associated
vesicles.

 Usually closer to the nucleus

and varies with type and activ-
ity of the cell.

 All proteins exported from the

cell are processed in the Golgi
complex.
107
Golgi Complex

 The Golgi complex consists of

flattened membranous saccules
and cisterns (3-20) that commu-
nicate with the ER and acts as a
receptacle for hormones and oth-
ers substances that the ER pro-
duces.

108
 Golgi Complex
 Golgi apparatus

 Receives molecules made in the ER

 Modifies the molecules with enzymes

 Sorts, packages and directs to correct location

Structure of Golgi Apparatus
Structure of Golgi Apparatus
Structure of Golgi Apparatus
 Golgi Complex
 GA function by receiving proteins from the rER and distributes
them to other organelles or out of the cell (receiving, processing,
packaging, and shipping)

 The Golgi apparatus processes the sugar side chains of secreted

and membrane glycoproteins and sorts the proteins for transport to
other parts of the cell.

 There is a well defined entry point for ER membranes, the cis face
of the Golgi apparatus membrane stacks, and an exit point, the
trans face of the stack.
 Golgi apparatus or Golgi body consists of stacks (cisternae) of
membranes enclosing a lumen.
 Membrane vesicles come from the ER and fuse with the Golgi apparatus.
 As a result of a series of vesicle-budding and fusion events, the membrane
molecules and soluble proteins in the lumen pass through the stacks of Golgi
apparatus from one side to the other.

 During this passage, Golgi enzymes, retained in specific layers of the Golgi ap-
paratus by trans membrane anchors, modify the sugar side chains of secretory
and membrane proteins.

 On the downstream side of the Golgi apparatus, processed proteins segregate

into different vesicles destined for lysosomes or the plasma membrane.
 Vesicles join on or bud off at the edges of the cis and trans cisternae , respec-
tively , and transfer the contents between adjacent stacks in the middle of the
Golgi body.
 Golgi Complex
Functions of Golgi complex
 Completes post translational modifications and packages and
places an address on products that have been synthesized by
the cell.

 Forms secretory vesicles that discharge processed proteins via

exocytosis into extracellular fluid.

 Forms membrane vesicles that carry new molecules to the

plasma membrane and other organelles, such as lysosomes.

115
Secretory Pathway of GA
Secretory Pathway of GA
Rough ER and Golgi complex

118
Insulin hormone secretion as example
Mitochondria
 Sausage shaped micrometer in size

 The mitochondria are literally the

“power plants” of the cell, capable
of producing the energy rich com-
pound ATP, which is required for
various cellular activities.

 The mitochondria require oxygen

to produce energy (ATP) from food
stuffs.

119
 Mitochondria (“powerhouse”)…

 Mitochondria synthesize ATP and thus provide the energy

needed to power many vital cell functions.

 They contain there own DNA (maternally derived), which

codes for a number of the enzymes needed for oxidative phos-
phorylation and RNA needed for the transcription and transla-
tion of mitochondrial DNA.

 Mitochondria can self-replicate during times of increased cel-

lular energy demand or before cell division.

120
 Mitochondria (“powerhouse”)…
 Has two membrane an outer and an inner, the inner membrane
projects folds, termed cristae, into the interior of the mitochon-
drion.

 The interior of mitochondria (i.e., matrix) contains the en-

zymes involved in the citric acid cycle and those involved in
oxidation of fatty acids.

 In addition to producing ATP, mitochondria can serve as a site

for sequestration of Ca++.

121
 Mitochondria (“powerhouse”)…

 Mitochondria are usually located within the cell where utiliza-

tion of energy is more intense.

 A cell may have as few as a hundred or as many as several

thousand mitochondria, depending on the activity of the cell.

 Active cells, such as those found in the muscles, liver, and

kidneys, which use ATP at a high rate, have a large number of
mitochondria.
 By contrast, red blood cells, which function primarily in the
transport of gases, contain no mitochondria.
122
 Mitochondria (“powerhouse”)…

123
 Mitochondria (“powerhouse”)…
 A class of diseases that
causes muscle weak-
ness and neurological
disorders are due to
malfunctioning mito-
chondria

 Worn out mitochondria may be an important factor in aging

Lysosomes
• Membraneous structures in the
cytoplasm that contains aggregates
of enzymes. Well developed in
macrophages.
Function:
•Degrade old dead cells and phago-
cytosis of microrganisms
• Digesting food or cellular in-
vaders,
• Recycling cellular components,
• Cell suicide
 Peroxisome
 Peroxisomes are similar physically to lysosomes, but they contain

oxidases rather than hydrolases.

 Several of the oxidases are capable of combining oxygen with hy-

drogen ions derived from different intracellular chemicals to form

hydrogen peroxide (H2O2)

126
General eukaryotic cell structure

 Peroxisomes

 contain oxidative enzymes that form and degrade hydrogen

peroxide

FA ------ H2O2 --- water + oxygen

Oxidation catalase
 Peroxisome Cont’d…
 Hydrogen peroxide is a highly oxidizing substance and is used in as-
sociation with catalase, another oxidase enzyme present in large
quantities in peroxisomes, to oxidize many substances that might
otherwise be poisonous to the cell.
 For instance, about half the alcohol a person drinks is detoxified by
the peroxisomes of the liver cells
 Catalase converts harmful substances to the body cells into harmless
ones.

128
Cytoskeleton

 Cytoskeleton

 Provides strength and structure to the cell

 Provides fundamental mechanistic components needed for

movement

 Three main types

 Actin (microfilament): generates contractile forces (i.e.

muscles); thinnest filaments

Cytoskeleton…

 Intermediate filaments: strengthen the cell mechanically

 Microtubules: hollow tubes that direct movement of dupli-

cated chromosomes in dividing cells

Cytoskeleton…
 Cytoskeleton…

 Complex network of interconnected filaments and tubules that

extends throughout the cytosol, from the nucleus to the inner
surface of the PM.

 Is proteinacious matrix that provide an architectural frame-

work to the cell and enable it to be correctly shaped.

 Is complex network of microtubules, actin filaments (microfil-

aments), and intermediate filaments.

132
 Cytoskeleton…
Functions of cytoskeleton:
 Motility (axons and dendrites in neurons, contractile fibers

in muscles, flagella in sperm cells).

 Pull the chromosome apart during cell division.

 Guide intracellular traffic of organelles.

 Supports the fragile membrane (sperm swim, leukocyte

crawl).

133
 Cytoskeleton…
 Three major types of protein filaments;
1. Actin filaments,
2. Microtubules, and
3. Intermediate filaments.

 Most eukaryotic cells contain all three

types of cytoskeletal filaments.

134
 Cytoskeleton…

Actin filaments:
 Contractile activity in muscle cells results primarily from an
interaction between two proteins: actin and myosin

 Actin is present in muscle as a thin (5–7 nm in diameter) fil-

ament composed of globular subunits organized into a dou-
ble-stranded helix.

 Are involved in endocytosis, exocytosis, and locomotion of

some cells.

135
 Cytoskeleton…

136
 Cytoskeleton…
Microtubules:
 Are tubular structures made up of
a heterodimer composed of tubu-
lin.

 Tubulin molecules are arranged to

form 13 protofilaments.

 Contain motor proteins powered

by hydrolysis of ATP.

 Provide basis for cilia and flagella.

137
 Cytoskeleton…

 Provide a rigid set of tracks

for the transport of a vari-
ety of membrane-enclosed
organelles and vesicles.

138
 Cytoskeleton…

 While microtubules provide an organized set of tracks along

which organelles can move, they do not directly generate the
force necessary for movement.

 The mechanical work depends on microtubule associated mo-

tor proteins, which attach to vesicles or organelles.

 Then motor protens “walk” along the microtubule, using ATP

to provide the needed energy.

139
 Cytoskeleton…

140
 Cytoskeleton…

141
Fast axonal transport of vesicles.
 Cytoskeleton…

 Cilia and flagella are highly specialized and efficient motility

structures built from microtubules and dyneins.

 The movement of a cilium or a flagellum is produced by the

bending of its core, which consists of nine doublet micro-
tubules surrounding a central pair of singlet microtubules.

142
 Cytoskeleton…
Intermediate filaments:
 Diameter of 10 –12 nm

 Provide mechanical
strength to the cell

 Unlike microtubules and

microfilaments, IFs are
assembled from a large
number of different pro-
teins.
143
Cytoskeletal system of the cell
 They are microfilament and mi-
crotubules, rigid threadlike struc-
tures dispersed through out the
cytoplasm.
Function of cytoskeletal system:
1. Maintain shape of the cells. eg.
Neurofibrils in axone
2. Serve as a transport system for
the movement of compounds and
organelles within the cell. eg ax-
oplasmic transport
3. Construct the mitotic spindle eg.
Centroils (9+3 triplets)
4. Provide for the support and
movement of cilia and flagella
(9+2 doublets)
5. Cell to cell contact: to fasten cell
membranes together
Microtubules organized as 9+2 doublets
144
 Nucleus
 Has a double membrane called the nuclear envelope separates
the nucleus from the cytoplasm.

 The outer membrane is studded with ribosomes and is contin-

uous with the membranes of the rough ER.

 The inner membrane is smooth and faces the intranuclear

space, or nucleoplasm.

145
 Nucleus…

 Both membranes are lipid bilayers similar to the plasma

membrane and outer membrane of the nuclear envelope is
continuous with rER.

 Many openings called nuclear pores extend through the nu-

clear envelope and control the movement of substances be-
tween the nucleus and the cytoplasm.

146
 Nucleus…
 Proteins needed for nuclear functions and newly formed RNA
molecules move from the nucleus into the cytosol through nu-
clear pores.

 Most cells have a single nucleus , even though skeletal muscle

cells and a few other types of cells have multiple nuclei.

 Inside the nucleus are one or more spherical bodies called nu-
cleoli that function in producing ribosomes.

147
 Nucleus…
 Each nucleolus is simply a cluster of protein, DNA, and RNA;
it is not enclosed by a membrane.

 Nucleoli are the sites of synthesis of rRNA and assembly of

rRNA and proteins into ribosomal subunits.

 Nucleoli disperse and disappear during cell division and reor-

ganize once new cells are formed.

148
 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 pro-
teins, enzymes, and other substances that are made by the cell.
 The nucleus is also the site of RNA synthesis.
 There are three kinds of RNA
Messenger RNA (mRNA), which carries the instruction from
DNA for protein synthesis to the cytoplasm
Ribosomal RNA (rRNA), which moves to the cytoplasm where
it becomes the site of protein synthesis
Transfer RNA (tRNA), serves as an amino acid transporter sys-
tem within the cell for protein synthesis.

149
 Nucleus (cont’d)
 DNA and RNA are made up of nucleotides
 Each nucleotide consists of a nitrogenous base, a sugar,
and phosphate.
 In DNA, nucleotides are composed of nitrogen contain-
ing bases purine (A, G) and pyrimidine (C, T) as well
as deoxyribose sugar conjugated by phosphate.
 In RNA, the pyrimidine base T is replaced by U and
the 5-carbon sugar is ribose.
 In addition to the chromatin, the nucleus contains one
or two round bodies called nucleoli. It is here that
rRNA is synthesized.
 The nuclear contents are surrounded by a double
walled nuclear membrane.
 The pores present in this membrane allow fluids, elec-
trolytes, RNA, and other materials to move between
the nuclear and cytoplasmic comportments.
150
The Cell Membrane (Plasma Membrane)
 The structure of a typical mammalian cell is bounded by a cell
membrane also called the plasma membrane or plasmalemma.

 It is a sheet-like structure that surround (enclose) the cell, separat-

ing the cellular contents from the ECF.

 It serves as a mechanical barrier that traps needed molecules

within the cell.

 It is selectively permeable to some substance and separates the

cell’s internal structures from the external environment.

151
 The Cell Membrane (Plasma Membrane)
 It is made up of proteins, lipids and carbohydrate.

 It is semipermeable, allowing some substances to pass through it and

excluding others.
 Its permeability can also be varied because it contains numerous

regulated ion channels and other transport proteins that can change
the amounts of substances moving across it.

152
The Cell Membrane (Plasma Membrane )

153
The Cell Membrane (Plasma Membrane)
155
The Plasma Membrane
The Plasma Membrane
 It is a sheet-like structure that surround (enclose) the cell, sepa-
rating the cellular contents from the ECF.
 It is entirely composed of proteins and lipids in a ratio of 55:42
respectively, and 3% of carbohydrates.
Percent proportion:
1. Proteins: 55 %
Phospholipids 25 %
2. Lipids: 42 % Cholesterol 13 %
Neutral fats 4%
3. Carbohydrate: 3 %

 The level of cholesterol determines rigidity of the membrane

157
 Membrane Structure: Protein to Lipid Ratio
varies from cell type to cell type

158
Membrane Components

Cholesterol is wedged between phospholipids molecules in

the plasma membrane of animals cells. It restrains the move-
ment of the phospholipids in warm temps. and maintains fluid-
ity by preventing tight packing at cold temps
159
Membrane Components (cont’d)
The lipid component of cell membranes is responsible
for the low permeability of cell membranes to water-
soluble substances such as ions, glucose, and amino
acids.

The protein component of the membrane consists of

transporters, enzymes, hormone receptors, cell-surface
antigens, and ion and water channels.

160
Lipid component of the cell membrane
 A plasma membrane is a fluid in
its nature, according to the fluid
Mosaic model of the membrane
 The cell membrane consists of an
ECF
organized arrangement of pro-
ICF teins, lipids and CHOs
 The major lipids are phospho-
lipids such as phosphatidyl
choline and phosphatidyl-
ethanolamine, and cholesterol.
 Lipids form the basic structure of
the membrane.
 The lipid molecules are arranged
in two parallel rows, forming a
lipid bilayer.

161
Lipid component of the cell membrane
Phospholipid structure
Lipid component of the cell membrane
Due to the amphipathic nature of phospholipids, spontaneously
assemble to form closed bilayers
 Lipid component (cont’d)
 The phospholipids compo-
nent is organized into a
double layer with their hy-
drophobic (tail) directed
toward the center of the
membrane and polar heads
directed out ward facing
ECF and ICF.
 Thus, phospholipid mole- Polar head (hydrophilic-likes water)
cules have both hy-
drophilic and hydrophobic
properties and are called
amphipathic
Non-polar tail (hydrophobic-hates water)
164
 Lipid component (cont’d)
The lipid molecules (primarily phospholipids) contain
a polar phosphate heads, soluble in water (hy-
drophilic) 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.
The lipid bilayer portion of the cell membrane is im-
permeable 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, fatty
acids, steroid hormones and drugs can penetrate this
portion of the membrane.
165
PROTEIN COMPONENT OF CELL MEMBRANES
Globular proteins are embedded in the lipid bilayer
and that these proteins participate in the transport of
lipid-insoluble particles through the plasma mem-
brane, some integral proteins act as carriers and chan-
nels.
Proteins in cell membranes may be either integral or
peripheral
Depending on whether they span the membrane or
whether they are present on only one side.

166
Membrane proteins are of two types
A. Integral or intrinsic proteins: interdigitated in the hy-
drophobic center of the lipid bilayer
Transmembrane proteins are integral proteins that span
the entire bilayer. Transmembrane 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
Integral proteins are transmembrane proteins, meaning
they span the lipid bilayer one or more times
 Thus, transmembrane proteins are in contact with both ECF
and ICF.

167
Membrane proteins (cont’d)

168
 Membrane proteins (cont’d)
B. Peripheral or extrinsic proteins: bind to the
hydrophilic polar heads of the lipid or on integral
proteins.
o They are loosely attached to either the intracellular
or extracellular side of the cell membrane
Peripheral proteins that bind to the intracellular
surface contribute to the cytoskeleton.
Peripheral proteins that bind to the external surface
contribute to the glycocalyx, a cell coat that is
composed of glyco-lipids and glyco-proteins to
cover the cell membrane.

169
Membrane proteins (cont’d)

170
a
 The functions of membrane proteins include the fol-
lowing:

Channel proteins: Channel proteins are integral proteins with

pores that allow passage of water and hydrophilic solutes
through the membrane
Carriers: Carriers are integral proteins that bind to glucose,
electrolytes, and other solutes and transfer them to the other
side of the membrane. Some carriers, called pumps, consume
ATP in the process
Enzymes: Enzymes in the plasma membranes of cells help to
produce second messengers and other signaling molecules

173
 Con’t…

Receptors: The chemical signals by which cells com-

municate with each other. Receptors are usually specific
for one particular messenger, much like an enzyme that
is specific for one substrate.
Second-messenger systems: When a messenger binds to
a surface receptor, it may trigger changes within the cell
that produce a second messenger in the cytoplasm. This
process involves both transmembrane proteins (the re-
ceptors) and peripheral proteins.

174
Many Functions of Membrane Proteins

Outside

Plasma
membrane
Inside
Transporter Enzyme Cell surface
activity receptor

Cell surface Cell adhesion Attachment to the

identity marker cytoskeleton

175
Many Functions of Membrane Proteins
Chemical
messenger

Channel
Recep- Enzyme Channel
tor

176
 Functions of Membrane Proteins
Transport

Enzymatic activity
catalyze chemical rxns

Receptors
for signal transduction

Intercellular adhesion

Cell-cell recognition

Attachment to cytoskeleton

and extracellular matrix

gives shape & strength

177
 Second Messengers
When a messenger binds to a surface receptor, it may trigger
changes within the cell that produce a second messenger in the cy-
toplasm
Let’s consider how the hormone epinephrine stimulates a cell.
Epinephrine, the “first messenger,” cannot pass through plasma
membranes so it binds to a surface receptor.
The receptor is linked on the intracellular side to a peripheral pro-
tein called a G protein
G proteins are named for the ATP-like chemical guanosine triphos-
phate (GTP), from which they get their energy

178
 Cont…
When activated by the receptor, a G protein relays the signal to
another membrane protein, adenylate cyclase
Adenylate cyclase removes two phosphate groups from ATP and
converts it to cyclic AMP (cAMP), the second messenger.
Cyclic AMP then activates enzymes called kinases in the cytosol.
Kinases add phosphate groups to other cellular enzymes.
This activates some enzymes and deactivates others
Either way, it triggers a great variety of physiological changes
within the cell.

179
Cont…
Membrane carbohydrates
 Attached invariably on the outside surface of the
membrane, binding with protruded integral proteins
and lipid, they form glyco-proteins and glyco-lipid
(glycocalyx or cell coat ) respectively.
 They play a role in
1. Antigenic activity in ABO blood groups
2. Cell to cell attachment
3. Act as receptors for NTs, hormones and drugs

181
 FLUID MOSAIC MODEL

FLUID- because individual phospholipids and proteins can

move side-to-side within the layer, like it’s a liquid.
MOSAIC- because of the pattern produced by the scattered
protein molecules when the membrane is viewed from
above.
182
Function of the plasma membrane
1. Separates cellular contents from the ECF
2. Regulates the passage of substances in and out. It is semi-per-
meable allowing some subs to pass through it excluding others.
This creates unequal distribution of ions on both sides of the
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 & muscles.
6. Involved in the regulation of cell growth and proliferation.

183
 Membrane junctions
 Junctions between cells are points of contact between cells that allow
them to behave in a coordinated manner.
A. Desmosomes:
 Consist of a region between two adjacent cells plasma membranes sepa-
rated by about 20 nm.
 Characterized by accumulations of protein known as “dense plaques”
along the cytoplasmic surface of the plasma membrane.
 These proteins serve as anchoring points for cadherins.
 Cadherins are proteins that extend from the cell into the extracellular
space, where they link up and bind with cadherins from an adjacent cell.
 Keratin filaments anchor the cytoplasmic surface of desmosomes to in-
terior structures of the cell.
 Desmosomes hold adjacent cells firmly together in areas that are
subject to considerable stretching, such as the skin.
 Desmosomes…

Desmosomes: intercellular rivets (holding)

 Creating tight bonds b/n cells, but allow fluids to pass

through intercellular spaces.

 Desmosomes (Anchoring) Junctions
Cell to cell or cell to CT • They maintain tissue integrity
matrix by providing strong intercellular
Anchoring junctions adhesion and acting as a link be-
(CAMs: cadherins) tween the cytoskeletons of adja-
Desmosomes
Adherens junctions cent cells.

Cell matrix attachments

(CAMs: integrins)
Hemi-desmosomes
(half-desmosomes)
Spot desmosomes or
focal adhesions (attach cells
to their basal laminas.)

186
B. Tight junction: forms when the extracellular surfaces of two
adjacent plasma membranes join together so that no extracellular
space remains between them.
oMost epithelial cells are joined by tight junctions near their apical
surfaces.
o In tight junctions, plasma membrane proteins attach in zipper-like
fastenings; they hold cells together so tightly that the tissues are
barriers (e.g., epithelial lining of stomach, kidney tubules).
 Tight (occluding) junctions
 Complete barrier (block wall)
 Fusion of adjacent cell mem-
branes via Claudine & oc-
cludin
 Found in
 Blood brain barrier
 GI tract, kidneys

188 Tight vs. leaky epithelium

Movement of substances across tight and leaky epithelia

189
C. Gap junction: consists of protein channels linking the cytosols
of adjacent cells.
The two opposing plasma membranes come within 2 to 4 nm of
each other.
Proteins called connexins from the two membranes to join, form-
ing small, protein-lined channels linking the two cells.
The small diameter of these channels (about 1.5 nm) limits what
can pass between the cytosols of the connected cells to small mole-
cules and ions, such as Na+ and K+, and excludes the exchange of
large proteins.
It is found in heart muscle cells, where they play a very important
role in the transmission of electrical activity b/n the cells
 Gap (communicating) Junctions
• Cylindrical proteins form channels

• Can open and close

• Electrical synapses

• Rapid transfer of signals in cardiac &

smooth muscle

• Are important for exchange of molecules

and ions between cells.
• Formed by transmembrane protein rings
called connexins.
• In cardiac muscles and smooth muscle elec-
trical impulse flows from cell to cell
through gap junction.
• Gap junctions thus permit the rapid propa-
gation of electrical activity from cell to cell
and the exchange of various chemical mes-
sengers.
191
Gap junction…
 Intercalated discs
Cardiac muscle

Intercalated discs: contain two

types of specialized junctions:
(a) Desmosomes (which act
like rivets & hold the cells
tightly together) and
(b) Gap junctions (which
permit action potentials to
easily spread from one
cardiac muscle cell to
adjacent cells)

193
 Intercalated discs…

Cardiac muscle
(myocardium)

194
Thank You!

195