Human Physiology

(PHYL)

1
 CHAPTER :
General Introduction and
Cell Physiology

2
 Chapter outlines
• Definition and historical background of physiology
• Levels of organization of the human body
• Composition of the human body
• Homeostasis and feedback systems
• Generalized Cell physiology
• Fluid compartments of the human body

3
 Learning Objectives

At the end of the session students will be able to:

Define the subject matter of physiology

Identify the branches of physiology

Explain the historical background of physiology

Define the principles of homeostasis

Identify homeostatic values of human body

Describe the functional structures of cell membrane and

cell organelles
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 Introduction to Human Physiology
What is Physiology
The term physiology literally means study of nature
/knowledge of nature (Greek: physis = nature; logia=study
of)

Physiology is the study of the normal functioning of a

living organism and its component parts, including all its
chemical and physical processes

It is sometimes called the science of regulation of

physiologic parameters of the body

It is the study of mechanical, physical and biochemical

properties of living organisms
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 Introduction cont’d...
Physiology also deals with the integrated activities of different
organs and organ systems, and the conditions which determine
normal functions of body parts.
• An important part of physiology is understanding how different
parts of the body are controlled, how they interact, and how they
adapt to changing conditions.

Fields of Physiology:
Fields of physiology range from simple viral physiology,
bacterial physiology, cellular physiology to the most complex
human physiology
Human physiology is the study of function of human body parts
(cells, tissues, organs & organ systems)
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 Introduction cont’d...
• Historical background: physiology is an experimental
science to which a number of scientists contributed a lot.

• William Harvey in 1628, correctly described the direction of

circulation of blood and structures of the circulatory system.

• Claude Bernard, a French physiologist in the 19th C.

described that every cell in the body is bathed with the fluid
environment called extra cellular fluid (ECF).
– ECF contains all the needed substances for cells.
– He called ECF is the internal environment of the body,
milieu interior in French.

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 Introduction cont’d…

• The concept of a relatively stable internal environment

(=concept of homeostasis) was developed by the French
physician Claude Bernard in the mid-1800s

• Walter Cannon, another great physiologist of the 1st half of

20th century(1929), termed the maintenance of constant
conditions in the ECF as homeostasis.

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 Introduction cont’d...
Relationship between physiology and other sciences
Physiology has a strong link with disciplines like:
Anatomy, Biochemistry, Pathology, Pharmacology,
Physics etc
Physiology as a quantitative science
» Physiologists are constantly trying to measure
changes occurring in living organisms
» All physiological parameters are expressed in
numbers and units (length, volume, weight,
temperature, etc)

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10
• The term homeostasis is used by physiologists to mean that
maintenance of static or constant conditions in the internal
environment (ECF).

• 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.

• Homeostasis is the maintenance of a steady state in the body

despite changes in the external environment.

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 Homeostasis cont’d…

• Essentially all organs of the body perform their functions to

maintain constant conditions in the ECF.
• For example
– Lungs maintain the normal concentration of respiratory
gases in blood.
– The CVS transports required substances and removes waste
produces,
– The kidneys maintain constant ionic concentration and
– The GIT provides nutrients.

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 Homeostatic Control Mechanisms

3 Input: Control
center 4 Output:
Information Information sent
sent along along efferent
afferent pathway to
pathway to

Receptor (sensor) Effector

2
Change
detected
by receptor

5 Response of
effector feeds
back to influence
1 Stimulus: magnitude of
Produces I mb stimulus and
al a
change nce returns
in variable variable to
homeostasis
Variable (in homeostasis)
I mb
al a
nce

13
 Homeostasis cont’d…

• Examples of Homeostatically Regulated Variables include:

– Body Temperature
– Blood Composition (ions, sugars, proteins, etc)
– Concentrations of O2 and CO2 in the blood
– Acid-Base balance (pH)
– Blood osmolarity
– Blood pressure, cardiac output, cardiac rate
– Respiratory rate and depth

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 Disturbances of homeostasis

 Deviations in normal ranges = pathology

• Hypo- or hyperthermia,
• Hypo- or hypercapnea
• Acidosis or alkalosis,
• Hypoxia or hyperoxia
• Hypo- or hypercalemia
• Hypo- or hyperglycemia

15
 Toxic Cancer
Chemicals Autoimmune
Trauma Disease
Viruses Sickle cell anemia
Bacteria Diabetes

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 Regulatory systems of homeostasis
 There are two systems in the body designed for
controlling body’s homeostasis:
1. The nervous system and
2. The endocrine system
 However, their manner of regulation varies.
 Common Properties of Hormones and Neurotransmitters
• Both are released in small amount
• Both have receptors on the target organs
• Both act by altering their target organs
• Both work towards common goal →Homeostasis

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 Homeostasis cont’d…

• But there are differences i.e.:-

– Nervous regulation is faster
– That of the hormones is slower
– Nervous regulation effects are diffused
– That of the hormones is mostly localized

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 Homeostasis regulation cont’d…

1. The nervous 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.
• Reflex arc is a path of neural reflex

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  The reflex arc is composed of five structures:

Stimulus
Stimulus(Mechanical,
(Mechanical,chemical,
chemical,thermal,
thermal,etc)
etc)

Receptor (Neural transduction)

Sensory System

Integrating center (Brain and spinal cord)

Motor System (FB)

Effectors (Muscle, gland) =Desirable biological responses20

 Homeostasis cont’d…
2. The hormonal regulatory mechanism
– Hormones are chemical messengers secreted by endocrine
glands, and transported via blood to the target organs including
other glands.
– 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

22
 Blood glucose homeostasis
1.
The
•
Gly Liver IT e
•
Gly cogene 2 . G
lu c os
• tion
Glu cogeno sis G
o r p
co n l a bs
eog ysis
en e
sis
Normal BGC
4. Brain
70-125 mg/dl All neurons
Utilize glucose

K id n ey s
3. se
Gluco ption
or
rea b s
5. Hormones
Hyperglycemic hormones
Hypoglycemic hormone

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Normal Ranges of Some Important Parameters
1. Body fluid volume = 42 L
ECF = 14L(IV=3.5L,ExV=10.5l)
ICF = 28L
2. Osmolality = (275 – 295 Mosm/kg)
3. Body T. = 36.5 – 37.49OC
4. pH = 7.35 – 7.45
5. Blood Gases
PCO2 = 35 – 45 mm Hg
PO2 = 40 – 104 mm Hg
6. Electrolytes (ECF)
Ca2+ = 10 mg/dL or 5 meq/L
K+ = 4 meq/L
Na+ = 142 meq/L
Cl- = 103 meq/L
HCO3- = 27 meq/27 24
 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 – 140 mm Hg)
Diastolic pressure = 80 mm Hg (60 – 90 mm Hg)
Pulse pressure = 40 mm Hg
Mean BP = 96 mm Hg
Pulmonary AP = 25/10
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)= 12-18 g/dl in Females, 14-20 g/dl in Males
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Normal values for electrolytes

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• Feedback Control Mechanisms of the
Homeostasis

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• The human body has thousands of control systems that
operate to keep homeostasis in it.
• Feedback control mechanism is a means by which our
body tries to maintain its homeostatic environment.
• There are two main types of feed back mechanisms:
A. The Negative Feedback Mechanism (NFM)
B. The Positive Feedback Mechanism (PFM)

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1. Negative Feedback Mechanism (NFM)
 Negative Feedback Mechanism (NFM)
– Negative feedback is the initiation of responses that counter
deviations of a controlled variable from its normal range and it
is the major control process used to maintain a stable internal
environment.

– 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 the respiratory center, which has an effect on
decreasing PCO2 in blood to normal via increasing Pulmonary
ventilation rate .
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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 NFM 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

1-31
 Human Thermoregulation

• Brain senses change in blood temperature

– if overheating, vessels dilate in the skin and sweating begins
– if too cold, vasoconstriction in the skin and shivering begins
1-32
 NFM cont’d…
• A negative feedback control system contains the
following elements:
1. A set point value, which is at the center of the normal
range of a variable and is treated by the control system as
the target value
2. Sensors that continuously monitor the controlled variable
3. A comparator (control center), which interprets input
from the sensors to determine when deviations from the
set point have occurred
• The comparator initiates a counter response
4. Effectors are the mechanisms that restore the set point to
its normal level

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34
2. The Positive Feedback Mechanism (PFM)

• It works by producing an effect which enhances or repeats the

same action like that of the starting stimulus.
– Self-amplifying change
• leads to change in the same direction
• The PFM is also called vicious circle.
• Normal way of producing rapid changes
• occurs with,
– childbirth,
– blood clotting, protein digestion, and
– generation of nerve signals
• Most of the time PFM is part of overall negative feedback
mechanism
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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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 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
LH-surge immediately before ovulation 38
 PFM cont’d…
4. Labor during child birth, uterine contraction is
enhanced as the head of the baby stretches the cervix
generation of action potentials AP reaches
hypothalamus another AP posterior pituitary 
release of oxytocin into the blood contraction of
uterine muscle more and more stretching and more
and more contraction.

• The only way to stop this kind of phenomenon is

removing the stimulus

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An Example of Positive Feedback:
Giving Birth

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41
 The elemental composition of the human body can be looked at from
the point of view of either mass composition, or atomic composition.

 To illustrate both views, the adult male human body is approximately

57% water, and water is 11% hydrogen by mass but 67% hydrogen by
atomic percent.

 Thus, most of the mass of the human body is oxygen, but most of the
atoms in the human body are hydrogen atoms.

11/20/24 42
 Composition of the human body
 The main elements that compose the human body are shown from
most abundant (by mass) to least abundant.

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 Composition of human body
 Body composition may also be analyzed in terms of molecular
type (e.g., water, protein, connective tissue, fats (or lipids) apatite
(in bones), carbohydrates (such as glycogen and glucose) and
DNA.
 In terms of tissue type, the body may be analyzed into water, fat,
muscle, bone, etc.
 In terms of cell type, the body contains hundreds of different types
of cells, but notably, the largest number of cells contained in a
human body (though not the largest mass of cells) are not human
cells, but consist of bacteria (bacterial cells) residing in the normal
human gastrointestinal tract.
 What is the largest number of human cell?

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Levels of organization of human body
Chemical level (H+, Na+ Ca2+....form molecules)
Muscle cells
Nerve cells
Cells 4 types Epithelial cells
Cells in the connective tissues
Muscle tissue
Tissues 4 types Nerve tissue
Epithelial tissue
connective tissues
Organs: are structures that are made of two or more different
types of tissues. They have specific functions
and a defined shape. Example: Heart, lungs
Organ system: Example: Respiratory system, CVS

Organism: e.g., Human 45

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 Levels of Body Organization cont’d...
• A cell is a basic structural and functional unit of life
– It is the smallest living unit of human body
• Our body is an aggregate of about 100 trillions of different types
of cells and extracellular matrix
• The cells of human body are bathed within the fluid environment
called extracellular fluid (ECF) that fills the space between cells
• A tissues are group of cells and surrounding
environment(Extracellular matrix), which work together to
produce a specific function
• The term tissue is also often used, as in clinical medicine, to mean
the aggregate of various cellular and extracellular components that
make up a particular organ (for example, lung tissue or liver tissue)

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Part II

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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

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Prokaryotes: (Eg. bacteria) Eukaryotes:

 No nucleus  Genetic material mostly in nucleus

 Smaller (1-10 m)  Larger (10-100  m)

 No cytoskeleton  Cytoskeleton present

 Generally no membrane-bound  Membrane-bound organelles

organelles present
RNA and protein synthesis in  RNA synthesis in nucleus, protein
same compartment synthesis in the cytoplasm

 Small circular chromosome  Multiple linear chromosomes

 Generally very small

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A GENERALIZED CELL

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 Generalized cell
Components of cells:
 A typical cell has two parts: nucleus and cytoplasm.
 The nucleus is separated from the cytoplasm by a nuclear
membrane
 The cytoplasm is separated from the surrounding fluid
(ECF) by the plasma membrane
 The different substances that make up the cell are collectively
called protoplasm.
Protoplasm:
 Composed mainly of five basic substances: water,
electrolytes, protiens, lipids and carbohydrates.

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Components of cells 53
 Cell membrane/ plasma membrane
• A sheet-like structure that surround (enclose) the cell,
separating the cellular contents from the ECF.

• Delimits the intracellular fluid within the cell from the

extracellular fluid and also the cell from the surrounding

• They form barriers between different cellular compartments

and define inside from outside

• Without this separation, cells would not be able to function,

and as such, proper membrane structure and function is
essential for life.
54
 The plasma membrane cont’d…
Biological membranes are complex mixtures of lipids and
proteins
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 tats 4%
3. Carbohydrate: 3 %

 The level of cholesterol determines rigidity of the membrane

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 Function of plasma membrane:
1. Separates cellular contents from the ECF
2. Regulates the passage of substances in and out. It is
semi-permeable allowing some substances 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 and muscle.
6. Involved in the regulation of cell growth and
proliferation.

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 A. 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 organized arrangement of
proteins, lipids and CHOs
• Lipids form the basic structure of the membrane.
• The lipid molecules are arranged in two parallel rows, forming
a lipid bilayer.

Figure: Lipid bilayer

Component of the cell
membrane. Polar head
faced the fluid
compartments and non-
polar tails hide themselves
in the interior. 57
 Lipid bilayer of the plasma membrane
• Basic structure of the plasma membrane is a lipid bilayer
(double-layered film of lipids each layer only one molecule
thick)
• Interspersed in this lipid film are large globular protein
molecules
• The basic lipid bilayer is composed of phospholipid molecules
• Phospholipid molecules are amphipathic (have hydrophilic &
hydrophobic ends)
• The major lipids are phospholipids such as phosphatidyl
choline and phosphatidyl-ethanolamine, and cholesterol

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Fluid Mosaic Model of Cell Membrane

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 Lipid …cont’d
• It is believed that globular proteins are embedded in the lipid
bilayers and that these proteins participate in the transport of
lipid-insoluble particles through the plasma membrane, some
integral proteins act as carriers and channels.

• The cell membrane is surrounded by a cell coat or glycocalyx,

which is made up of glycolipids and glycoproteins.

• The cell coat is the site of hormonal receptors and antigenic

activity in ABO blood groups.

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 Lipid …cont’d
• The lipid molecules (primarily phospholipids) contain a polar
phosphate heads, soluble in water (hydrophilic) and a non-
polar tails that does not mix with water (hydrophobic).
• The physical orientation of the lipid bilayer structures is that
the hydrophilic ends of the lipid molecules line up facing the
ICF and ECF.
• The hydrophobic tails of the molecules face each other in the
interior of the bilayer.
• The lipid bilayer portion of the cell membrane is impermeable
to water and water soluble substances such as ions, glucose,
urea and others.
• On the other hand, fat soluble substances such as O2, CO2,
alcohol and drugs can penetrate this portion of the membrane.
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 Hydrophilic

Hydrophobic

Figure Phospholipid molecule 62

The hydrophilic - the glycerol backbone and the phosphorylated
head group of the phospholipids makes association with water.
The other end is soluble only in fats; that is, it is hydrophobic –
the two hydrocarbon chains of the fatty acid portion is
Hydrophobic makes the middle of the cell membrane 63
 B. Protein component of Cell Membrane (1)
• According to fluid Mosaic model, the plasma membrane are also
composed of globular proteins embedded in the lipid bilayer
• Membrane proteins are two types:

A. Integral or intrinsic proteins:

– Interdingitated in the hydrophobic center of the lipid bilayer
i. Transmembrane proteins: are integral proteins that span the
entire bilayer.
– It serve as: - Channels through which ions pass
- Carriers which actively transports
material
- Pumps which actively transport ions
- Receptors for NTs and hormones

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 B. Protein component of Cell Membrane (2)

ii. Integral proteins that are present only on one side of the
membrane, serve primarily as enzymes.
• Example: Adenylate cyclase

B. Peripheral or extrinsic proteins:

– Bind to the hydrophilic polar heads of the lipid or on
integral proteins.
– Peripheral proteins that bind to the intracellular surface
contribute to the cytoskeleton.
– Peripheral proteins that bind to the external surface
contribute to the glyco-calyx
 i.e. a cell coat that is composed of glycol-lipids and
glycol-proteins to cover the cell membrane
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Plasma Membrane

66
67
 C. Carbohydrates components of PM
• Attached invariably on the outside surface of the membrane,
binding with protruded integral proteins and lipid, they form
glyco-proteins and glyco-lipid (glycocalyx) respectively.
• They play a role in:

1. Immune reaction (antigenical importance),

2. Cell to cell attachment and

3. Act as receptors for NTs, hormones and drugs

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 The Cytoplasm
The cytoplasm surrounds the nucleus and it is here the work of the
cell takes place.
It is essentially a colloid solution that contains water, electrolytes,
suspended proteins, neutral fats, and glycogen molecules
Major intracellular electrolytes: K+, Mg2+, PO43-, SO42- and
HCO3-
Smaller quantities: Na+, Cl- and Ca2+
These electrolytes facilitate the generation and transmission of
electrochemical impulses in nerve and muscle.
Intracellular electrolytes are also participate in reaction for cellular
metabolism
Inner organs of the cell or organelles: Ribosome, ER, Golgi
Apparatus, Mitochondria, lysosomes, and cytoskeletal system

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 Cytoplasm …cont’d
 Is the portion of the cell found
between nucleus and cell
membrane
 Contains organelles and
cytosol
 Cytosol is the fluid portion of
cytoplasm
 Organelles are specialized
compartments or subunit
within a cell that have specific
functions
 An organelle is usually
separately enclosed within its
own membrane

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 The nucleus
• The control center for the cells.
• Contains the genes, which are units of heredity.
– Chemically each gene consists of a highly compressed DNA in
the form of chromosomes
– Genes control cellular activity by determining the type of
proteins, enzymes, and other substances that are made by the
cell.
• The site of RNA synthesis.

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 The nucleus…cont’d
• There are three kinds of RNA
– Messenger RNA (mRNA): carries the instruction from
DNA for protein synthesis to the cytoplasm
– Ribosomal RNA (rRNA): moves to the cytoplasm where it
becomes the site of protein synthesis
– Transfer RNA (tRNA): serves as an amino acid transporter
system within the cell for protein synthesis.
• DNA and RNA are made up of nucleotides
– In DNA, nucleotides are composed of nitrogen containing
bases purine (A, G) and pyrimidin (C, T) as well as
deoxyribose sugar conjugated by phosphate.

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73
 The nucleus (cont’d)
• In RNA, the pyrimidin 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, electrolytes,
RNA, and other materials to move between the nuclear and
cytoplasmic comportments.

74
 Function of nucleotides

1. Building units of nucleic

acids- DNA, RNA
2. High energy molecules
(ATP, GTP)
3. Biosynthetic mediators
(UDP-glycogen-
immediate precursor of
glycogen )
4. Regulator of chemical
reaction in the cell e.g.,
cAMP
5. Act as coenzyme (NAD,
FAD)
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76
• Embedded within the cytoplasm are organelles or inner organs
of the cell.
• These include the ribosomes, endoplasmic reticulum (ER) golgi
apparatus, mitochondria, lysosomes, peroxisomes and the
cytoskeletal system (microtubles and microfilaments).

77
Ribosome:
• They are not membrane bounded
• Sites of protein synthesis in the cell
• Small particles composed of rRNA and proteins
• Found in two forms: scattered in the cytoplasm and clustered
(joined) to form functional units called poly ribosome
– Found as free ribosomes in the cytosol or bound to rough
endoplasmic reticulum (RER)
Endoplasmic reticulum (ER):
 An extensive membranous structure that connects various
parts of the inner cell.
 It also connected with the nuclear membrane
 There are two types of ER: rough ER and smooth ER.
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 Endoplasmic reticulum (ER)

• Rough Endoplasmic reticulum (RER) or

granular ER
 The surface is coated with ribosomes
 Concerned with synthesizes of proteins in the cells
(ribosomes)
– Segregate proteins that being are exported from the
cell
 RER is prominent in cells that are secreting hormones
and enzymes (example, pancreas cells)

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 Endoplasmic reticulum (ER)
• Smooth ER:
 Free of ribosomes
 Glycogen storage
 Mobilization of glucose from glycogen in liver cells
(glucose-6- phosphatase enzyme)
 Lipid biosynthesis: synthesize lipids, especially
phospholipids and cholesterol
 Calcium ion storage: in muscle special smooth ER
(sarcoplasmic reticulum) accumulates ca++ ions (trigger for
muscle contraction)
 Detoxify (metabolize )substances, such as steroids and
drugs, that might damage the cell
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Rough and Smooth ER

81
 Golgi Complex
 Is a set of stacked membranes compartments found near the
nucleus
 Golgi apparatus finishes proteins: adds sugar molecules to side
groups; routes them to the right destination some go to
mitochondria, others to lysosomes, some to cell membranes, etc
 Packages proteins into vesicles for secretion or internal use
 Consists of flattened membranous saccules and cisterns that
communication with the ER
 Acts as a receptacle for hormones and others substances that the
ER produces.
 It then modifies and packages these substances into secretary
granules.
 These secretary granules make out of the Golgi Complex into the
cytoplasm
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 Golgi complex...cont’d
 It is though to produce large CHO molecules which is needed to
combine with protiens to form Glyco-protiens
 Many pro-hormones and inactive enzymes produced in the rER
are converted into active hormones and enzymes in the Golgi
Complex by proteolytic enzymes.
 The forming face of golgi apparatus, where vesicular tubular
compartment (VTCS) from the ER arrive, is called the cis-golgi
network (CGN)
 The trans-golgi network (TGN) is the part of golgi apparatus
from where vesicles leave to be distributed to their next
destination

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Golgi apparatus

84
Endoplasmic reticulum and Golgi complex

85
 Rough ER and Golgi complex

86
Fig. Synthesis of protein hormone
 Mitochondria
Second largest organelle
Usually many per cell; the distribution depends upon the
activity of the cell; the more active the cell, the more
mitochondria.
Rod shaped, enveloped by double membrane
An outer membrane encloses the periphery
An inner membrane is enfolded to form the cristae,
containing a number enzymes which aid in the production
of ATP
The mitochondria are literally the “power plants or power
house” of the cell, capable of producing the energy rich
compound ATP

87
 Mitochondria
• The mitochondria require oxygen to produce energy (ATP)
fromfood stuffs.
• Its primary function is production of ATP
• Have small amounts of DNA; make their own proteins from
their own genes
• Mitochondria contain their own genetic system
 mDNA encodes for some proteins of the mitochondria
 mDNA inheritance is maternal

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 Lysosomes
• Lysosomes are vesicular organelles that form by breaking off from
the Golgi apparatus and then dispersing throughout the cytoplasm.
• Surrounded by a single membrane and spherical in shape
• Are called suicide bags
 The lysosomes provide an intracellular digestive system that
allows the cell to digest
– (1) damaged cellular structures
– (2) food particles that have been ingested by the cell, and
– (3) harmful substances such as bacteria.
• It is surrounded by a typical lipid bilayer membrane and is filled
with large numbers of small granules 5 to 8 nanometers in
diameter, which are protein aggregates of as many as 40 different
hydrolase (digestive) enzymes per lysosome.

89
 Lysosomes …cont’d
Membrane bound organelles that contain hydrolases
(Hydrolytic enzymes; lipases, proteases, glycosidases,
nucleases etc )
 The membrane surrounding the lysosome prevents the
enclosed hydrolytic enzymes from coming in contact with
other substances in the cell and, therefore, prevents their
digestive actions.
 Is used to break down old proteins, many wastes, dead cells
and phagocytized foreign materials
 Kept acidic (PH  5) by the action of a proton pump, or H+
atpase

90
Lysosomes
…cont’d
 Membraneous structures in the
cytoplasm the contain aggregates of
enzymes.
 Well developed in macrophages.
Function:
• Degrade old dead cells and
phagocytosis of microrganisms

Lysosomes

91
 Peroxisomes
• Also called small bodies and they are spherical in shape
• Are membrane bound organelles containing enzymes;
oxidases and catalases
– Surrounded by single membrane
• Have protective role in that they secrete chemical that
converts harmful substances into harmless
– e.g., Catalase produced by peroxisomes change H2O2 to
H2O and O2
• Catalase is a type of oxidase which converts:

» H2O2 catalase H2O + O2

92
 Peroxisomes
 Are similar physically to lysosomes, but they are different in
two ways:
  They formed by self-replication (or perhaps by budding
off from the smooth endoplasmic reticulum) rather than
from the golgi apparatus
  They contain oxidases rather than hydrolases

93
 Cytoskeleton system of the cell
• They are microfilament and
microtubules, rigid threadlike
structures dispersed through out
the cytoplasm.
Function of cytoskeletal system:
1. Maintain shape of the cells. eg.
Neurofibrils in axon
2. Serve as a transport system for
the movement of compounds and
organelles within the cell. eg
axoplasmic 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 Microtubules organized as 9+2 94
membranes together doublets
 Cytoskeleton cont’d…
• The cytoskeleton is made up of three kinds of protein filaments:
• Microfilaments (cellular support, muscle contraction,
pseudopodia and amoeboid motion, microvilli of enterocytes)
– are long solid fibers with a 4 to 6 nm diameter that are made
up of actin protein molecules
– Filamentous (F) actin refers to intact microfilaments and
globular (G) actin refers to the unpolymerized protein actin
subunits
• Intermediate filaments (reinforce cell shape, fix organelle in
position, lining the nuclear envelope's interior)
– are 8 to 14 nm in diameter and are made up of various
protein subunits (eg. vimentin, keratin)
– form a flexible scaffolding for the cell and help it resist
external pressure (in their absence, cells rupture more easily)

95
 Cytoskeleton cont’d…
• Microtubules (provide the tracks for transport of vesicles,
organelles; cilia, flagella & spindle)
– are long, hollow structures of about15 nm in diameter
– are made up of two globular protein subunits: α-tubulin and
β- tubulin
– axonemes of the flagella and cilia are composed of
microtubules

96
97
• 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
98
 Transport through the cell membrane

• Cells have two categories of transport for the movement of

ions and small solute molecules across the plasma membrane
• These transport mechanisms are passive transport and active
transport
• Some of the transport process happens "passively" without the
cell needing to expend any energy; such processes are called
"passive transport processes“
• Other transport processes require energy (ATP) from the cell's
reserves to "power" them; these processes are called "active
transport processes"

99
 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

2. The movement of large molecules across cell membrane

takes place by vesicular transport (endocytosis and
exocytosis)
100
 Transport through the cell membrane

ECF ECF

ICF ICF

101
 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 protein mediated transport

• Examples: Substances that are transported by simple diffusion includes

CO2, O2, N2, steroids, urea, glycerol, ethanol alcohol, lipid soluble drugs
and ions through specific channels.

102
 Simple Diffusion
 Factors affecting the net rate of diffusion
a. Lipid solubility of the subs
b. Membrane permeability
c. Concentration difference
d. Pressure difference
e. Electrical potential difference of ions

 Membrane permeability is affected by

– Membrane Thickness
– Lipid solubility
– No of ion channels per unit area
– Temperature: T =  thermal motion of molecule
permeability
– MW

103
 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

Where, C = Change of concentration

S = Solubility in lipid
A = Surface area of the membrane
T = Temperature
D = Distance or membrane thickness
MW = Molecular wt of substances

104
Lipid bilayer of cell membrane

105
 2. Facilitated diffusion
 Carrier mediated transport
– Does not need cellular metabolic energy (ATP)
– it’s powered by thermal energy of the diffusing molecules
• Carriers are saturable
– Because there are limited numbers of carrier proteins in cell
membrane increasing the concentration gradient initially causes
increased diffusion rate but the transport system eventually
reaches saturation, when all the carriers are involved in
translocating molecules of solute
– At this point, additional increases in solute concentration do not
increase the rate of solute transport
• Carrier-mediated facilitated diffusion transport, like simple
diffusion, does not have directional preferences
– It functions equally well in bringing its specific solutes into or
out of the cell, depending on the concentration gradient
 2. Facilitated diffusion

 Transports substances down their concentration gradient

 large molecules & charged substances (ions and molecules)
cross plasma membrane by facilitated diffuse
 Examples: transport of glucose, proteins (Macromolecules)
 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

107
 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
108
Simple diffusion vs facilitated difusion

109
 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….AQ5) have been identified in the
body.

110
Osmosis

Figure: Osmosis: Mechanism

of Transport of Water
through the Cell Membrane

111
Summary of passive transport of
substances
•All the passive transport mechanisms tend to bring the cell into
equilibrium with the extracellular fluid
•Cells must oppose these equilibrating systems and preserve
intracellular concentrations of solutes, particularly ions, that are
compatible with life.

112
 4. 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

113
 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
– Carrier protein is anti-porter
• Primary active transport includes:
 Sodium-potassium pump or Na+/K+-ATPase
 Calcium pumps, Ca2+-ATPases
 H+/K+-ATPase
 Proton pumps, H+-ATPases

114
 Active transport …cont’d
Sodium-potassium pumps or Na+/K+-ATPases
• Are found in the plasma membrane 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+ out of the cell and 2K+ into the cell 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+ 115
pumped outward and K+ inward.
 Active transport …cont’d

Figure:# Primary active transport, Na+ - K+ ATPase

116
 10 Active transport …cont’d
Calcium pumps, Ca2+-ATPases:
 Are found in the plasma membrane, in the membrane of the
endoplasmic reticulum, and, in muscle cells in the sarcoplasmic
reticulum membrane
 Pump calcium ions from the cytosol of the cell either into the
extracellular space or into the lumen of these organelles

Ca2+ ATPase Plasma

Cytosol membrane
cc SER or
Ca2+
Sarcoplasmic
Ca2+
Reticulum
117
 10 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

118
 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

119
 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
– Carrier protein is symporter

120
 20 Active Transport…cont’d

Figure:# Secondary active transport, Na+ - Glucose Co-transport Mechanism

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

122
 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
 Vesicular (Bulk) transport across cell
membrane
 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 and pinocytosis

124
 Vesicular transport…cont’d

• Phagocytosis is the ingestion of large particles or

microorganisms, usually occurring only in specialized cells
such as macrophages, also called cell eating
• 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
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

125
126
 Vesicular transport…cont’d

Endocytosis
127
BODY
FLUID

128
 Learning Objectives

At the end of this chapter, students should be able to:

Describe body fluid compartments

Identify composition of body fluid

Define important terms involving in body fluid

Describe the tonicity of a solution

129
 Composition of Human Body

• The approximate composition of an average adult human per

body weight is that:
– Water = 60%
– Proteins = 18%
– Fats = 15%
– Minerals = 7%

130
 What is Body Fluid?
 The term refers to the body water + its dissolved substances

 BF comprises an average of 60% of total body weight

 The total body water in adult averages about 42 L

131
 Fluid Environment of the Cells
• About 60% of human body is made up of fluid
• In a 70kg man, there is 42 liters, distributed as:
1. Intracellular compartment: Fluid inside the cell (28L)
2. Extracellular compartment:(14 L)
• 2 Subdivisions:
– Blood plasma 2L
– Interstitial fluid 12L
• A cell is the basic structural as well as functional unit of life
• Cells are bathed with the fluid called ECF.
• This fluid contains an optimum amount of nutrients, gasses,
hormones, enzymes, water and electrolytes

132
 Body fluid compartments
• There are two major body fluid compartments or spaces:
 Intracellular fluid (ICF) = two thirds of the body water
 Extracellular fluid (ECF) = one third of the body water

• These two fluid compartments differ strikingly in terms of

their electrolyte composition

• But the fluid compartments solute concentrations (osmolarity)

are normally equal (no an osmotic difference between cells
cytoplasm and ECF)

133
 Body fluid compartments… cont’d
• The ECF further subdivided into two major sub compartments:
– The interstitial fluid and lymph, comprises three fourths of
the ECF

– The blood plasma, comprises about one fourth of the ECF

• The blood plasma, interstitial fluid, and lymph are
nearly identical in composition, except for the higher
protein concentration in the plasma

– In addition to above mentioned, ECF compartment

includes transcellular fluid that amounts to about 1% to 3%
of body weight
134
 Body fluid compartments… cont’d
– Transcellular fluids include
cerebrospinal fluid, aqueous
and vitreous humor humor
of the eye, secretions of the
digestive tract and
associated organs (saliva,
bile, pancreatic juice), renal
tubular fluid and bladder
urine, synovial fluid, and
sweat

– Transcellular fluids are not

plasma ultrafiltrates (as are
interstitial fluid and lymph);
so they have a distinct ionic
composition 135
Fig. Distribution of body water compartments in an
average young adult man weighing 70 kg 136
137
 Total body water
60% of body weight in adult

Intracellular Fluid (ICF) = fluid in the cells ECF= Fluid outside the cells
(2/3 TBW; 40% of body wt.) (1/3 TBW; 20% of body wt.)

ISF=Fluid that surround

Blood plasma (IVF)=Fluid the cell (3/4 of ECF)
within the blood Vessels
1/4 of ECF TBW : TOTAL BODY WATER
ICF: INTRACELLULAR FLUID
ECF : EXTRACELLULAR
FLUID
IVF : INTRAVASCULAR FLUID
138
ISF: INTERSTITIAL FLUID
Trans-cellular Spaces
 Are potential spaces containing small volume of body fluid

Lymph in the lymphatic vessels

CSF in the brain ventricles and central canal of spinal cord

Synovial fluid in Joints

Aqueous humor and vitreous body in the eye (intraocular

fluid)
Endo-lymph and perilymph in the inner ears

Pleural, pericardial, peritoneal fluids

Glomerular filter in the body

139
 Importance of Water in the body

 As a solvent: to electrolytes and dissolve nutrients

 Digestion and absorption requires fluid medium

 Transportation

 Temperature regulation

140
 Constituents of the Body Fluids
 BF composed of electrolytes, nutrients, respiratory gases,
hormones and vitamins in different proportion.
 Water is the universal solvent

 Solutes
– Electrolytes: inorganic salts, all acids and bases, and some
proteins
– Non-electrolytes: examples include glucose, lipids,
creatinine, and urea
 Electrolytes have greater osmotic power than non-electrolytes

 Water moves according to osmotic gradients.

141
 Constituents of the Body Fluids
• The ionic compositions of the plasma and ISF are similar
because they are separated by highly permeable capillaries
except,
 The protein composition of the plasma is much greater than
that of the ISF
 Because of the Gibbs–Donnan effect (asymmetric
distribution of anionic proteins) brings about small
asymmetries in the distributions of the permeable ionic
species (the concentration of Na+ in the plasma is between
5 and 10% greater than that in the ISF, and the
concentrations of Cl- and HCO3- in the ISF fluid are
between 5 and 10% greater than those in the plasma)

142
 Constituents of the Body Fluids
• There is the higher concentration of protein in the plasma than
in interstitial fluid (the capillaries have a low permeability to
the plasma proteins)
– Because of the Donnan effect, the concentration of
positively charged ions (cations) is slightly greater 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

143
 Constituents of the Body Fluids
– 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 proteins while the
negative charges of the plasma proteins repel the
negatively charged anions

• Intracellular fluid is separated from the extracellular fluid by a

cell membrane (highly permeable to water but not to most of
the electrolytes in the body)

144
 Constituents of the Body Fluids

• Intracellular fluid contains large amounts of potassium and

phosphate ions plus moderate quantities of magnesium and
sulfate ions (all of which have low concentrations in the
extracellular fluid)

• The intracellular fluid contains only small quantities of

sodium and chloride ions and almost no calcium ions

145
Constituents of the Body Fluids

ECF contains:
ICF • Nutrients: glucose, amino acids,
lipids
•Water
•High K+, Po43-, • Gases: O2, CO2
Mg2+ • Hormones
•Nutrients, gases • Enzymes
•Hormones • Water
• Minerals (High Na+, Cl- , Ca2+ and
HCO3-

Figure 1 Body Fluid Compartments and Their Major Content

146
The concentration of electrolytes, nutrients,
respiratory gases in the ICF & ECF

147
Electrolyte Composition of Body Fluids

148
149
 Factors Affecting Total Body Water
(TBW)
 Water is by for the largest single component of body that
makes up 60% TBWt.
 The percentage of water to total body weight varies for
different factors:
 Sex; adult men  60% of total body weight adult women
 55% of total body weight
 Age; neonate  70% of total body weight ; > 60 years men
52%, women 46% of total body weight
 A lean person has a high, and an obese person a low,
percentage of body weight that is water
150
 Water Homeostasis
Water Balance: To remain properly hydrated, water intake must
equal water output, so the body maintains a constant volume
•Water intake sources
– Ingested liquids (60% or 1400ml/day) and solid foods (30%
or 700ml/day) that have been absorbed from GIT.
This water called performed water (amounts 2100ml/day)
– Metabolic water or water of oxidation (10% or 200ml/day):
water produced through dehydration synthesis reactions of
anabolism Urine (60%)
•Water output
– Kidney excrete (Urine) = 1400ml/day (60%)
– Skin = 350ml/day Insensible losses (28%),
– Lungs = 350 ml/day
– GIT = 200 ml/day; {feces (4%),and sweat (8%)} 151
152
 …cont’d
• The most important means by which the body maintains a
balance between water intake and output is by controlling the
rates at which the kidneys excrete water (0.5 L/day to 20
L/day)

153
 Regulation of Water Homeostasis
a. The Thirst Mechanism
•Thirst is a powerful regulator of fluid consumption
•When water loss is greater than water gain, the resulting
dehydration stimulates thirst in at least 2 ways:
a. Dehydration =↑s blood osmotic pressure → stimulates
osmoreceptors in HT
• These receptors also stimulate the thirst center in the HT
b. Dehydration= ↓s BP → stimulates the release of Rennin by
JG-cells of the Kidneys
• Rennin promotes formation of Ang-II, an effect of which is
to stimulate the thirst center in HT
•Thus, when the thirst center stimulated, the sensation of thirst is
increased, fluid intake is initiated and normal fluid volume is
restored. 154
Regulation of Water Intake: Thirst Mechanism

155
 Regulation of Water Homeostasis
b. The Antidiuretic Hormone (ADH)
•Normally, fluid loss is adjusted by ADH and aldosterone
•ADH and Aldosterone → ↓s fluid loss
•ANP → causes diuresis

c. The Renal System

•Renal tubules control water balance by:
– Producing concentrated urine when there is a shortage of
water in the body; and
– Producing diluted urine when there is excess water in the
body

156
 Influence and Regulation of ADH
• Water reabsorption in collecting ducts is proportional to ADH
release
• Low ADH levels produce dilute urine and reduced volume of
body fluids
• High ADH levels produce concentrated urine (preserve body
water)
– Hypothalamic osmoreceptors trigger or inhibit ADH release
– Factors that specifically trigger ADH release include
Prolonged fever;
Excessive sweating,
Vomiting, or diarrhea;
Severe blood loss; and
Traumatic burns
157
158