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5/15/23

Transportation of substances in
living organisms

Vo Van Giau, Ph.D


Email: vvgiau@medvnu.edu.vn

To remain alive, a cell needs

O2, water,
Ø To provide nutrients for metabolism and
Transportation!

nutrient… growth;
Ø To supply O2 for respiration;
Taking Ø To regulate solute concentration and pH;
Ø To maintain an icon concentration
CO2, gradient;
toxin… Ø To secrete useful substances as enzyme,
hormones;
Eliminating Ø To eliminate toxic waste products…

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Outline
§ The basic of molecular transport phenomena: diffusion,
osmosis, and related processes
§ Movement of substances across cell membranes
§ Circulatory system and pathway of blood through the heart
§ Transport of oxygen and carbon dioxide during respiration
§ Transport and absorption in digestive system
§ Human excretory system

The structure of cells

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Plasma Membrane
• Plasma membrane: a thin, fragile
structure that separated cell from
the external world.
• Contain a lipid bilayer, and the
two dark-staining layers

Cellular membrane: Gatekeeper of the cell

o Ultrathin, dynamic, electrically, charged selectively permeable layer that


separates the cytoplasm from extracellular matrix
o Regulates what enters and leaves the cell
o Provides protection
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Selective permeability of the plasma membrane


Impermeable: unable to go
through
Permeable: most things can
pass through
Semi-permeable: only smaller
molecules can pass
Selectively permeable: only
molecules can pass
Cell membranes are selectively
permeable

The general structure of membranes is known as


“fluid mosaic model”
o It was first proposed by S.J.
Singer and Garth L. Nicolson in
1972 to explain the structure of
the plasma membrane.
o It still best accounts for the
structure and functions of the
plasma membrane as we now
understand!
o The phospholipid bilayer is like a
“lake” in which a variety of
proteins “float”
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Integral/peripheral and lipid-anchored proteins


Integral membrane proteins (transmembrane)
- Exposed to aqueous environment on both
sides of the membrane
- Used to transport molecules across membrane
- Acting as ion channels, ion pumps and
structural support; the peripheral proteins act
as cell identity markers.

Peripheral membrane proteins


- Located on surface of a membrane
- Acting as cell identity markers;

Lipid-anchored membrane proteins


- Attaching to one side of the membrane
through covalent bonds to lipid groups.
- Aiding in stabilizing the protein–membrane
interaction
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The phospholipid bilayer

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Transport proteins

• Chanel/pore proteins are embedded in the cells membrane and have a pore
for materials to cross
• Carrier proteins can change shape to move material from one side of the
membrane to the other

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Movement of substances across cell membranes


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Diffusion

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Diffusion through the cell membrane

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Solute molecules move across membranes

Four basic mechanisms by which solute molecules move across membranes 15

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SoluteSolute
Movement
Movementacross Cell
across Cell Membranes
Membranes
Energetics of Solute Diffusion
• Diffusion (khuếch tán) is a
spontaneous process in which a
substance moves from a region of
high concentration to a region of
low concentration.
• The free-energy change when an
uncharged solute diffuses across a
membrane thus depends on how
different the concentration is on
the two sides of the membrane.
• This difference is known as the
concentration gradient.
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SoluteSolute
Movement
Movementacross Cell
across Cell Membranes
Membranes
Formation of an Electrochemical Gradient

Electrochemical gradients arise from the combined effects of


concentration gradients and electrical gradients 17

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Diffusion through
Diffusion the
through the Lipid
Lipid Bilayer
Bilayer
Diffusion of Substances through Membranes
• Diffusion is an energy-independent process in which a solute moves down
an electrochemical gradient, dissipating the free energy stored in the gradient.
• Small inorganic solutes, such as O2 , CO2 , and H2O, penetrate the lipid
bilayer readily, as do solutes with high lipid solubility.
• Ions and polar organic solutes, such as sugars and amino acids, need
special transporters to enter or leave the cell.
• The smaller molecule tends to penetrate the lipid bilayer of a membrane more
rapidly than the larger one.
• Very small, uncharged molecules penetrate very rapidly through cellular
membranes.
• Larger polar molecules, such as sugars, amino acids, and phosphorylated
intermediates, exhibit poor membrane penetrability.
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Diffusion through
Diffusion the
through the Lipid
Lipid Bilayer
Bilayer
Diffusion of Substances through Membranes

• The substance must be present at higher concentration on one


side of the membrane than the other, and the membrane must be
permeable to the substance.
• A membrane may be permeable to a given solute either (1) because
that solute can pass directly through the lipid bilayer, or (2) because
that solute can traverse an aqueous pore that spans the membrane

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Diffusion through the Lipid Bilayer


The Diffusion of Water through Membranes
• Osmosis is the movement of water through a semipermeable
membrane according to the concentration gradient of water across
the membrane, which is inversely proportional to the
concentration of solutes.
• Semipermeable membranes, also termed selectively permeable
membranes or partially permeable membranes, allow certain
molecules or ions to pass through by diffusion.
• While diffusion transports materials across membranes and within
cells, osmosis transports only water across a membrane.
• The semipermeable membrane limits the diffusion of solutes in the
water. Not surprisingly, the aquaporin proteins that facilitate water
movement play a large role in osmosis, most prominently in red
blood cells and the membranes of kidney tubules.
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Diffusion through the Lipid Bilayer


The Diffusion of Water through Membranes

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Diffusion through
Diffusion theLipid
through the Lipid Bilayer
Bilayer
The Diffusion of Water through Membranes
• Aquaporins (AQP) are a small (~30 kDa monomers) integral membrane proteins that serve
as channels in the transfer of water, and in some cases, small solutes across the membrane.
• It was discovered in 1992 by Potor Agre of Johns Hopkins Uni and he was awarded Npbel
prize in 2003
• Structural analyses of the molecules have revealed the presence of a pore in the center of
each aquaporin molecule.
• Each aquaporin subunit (in the four-subunit protein) contains a central channel that is lined
primarily by hydrophobic amino acid residues and is highly specific for water molecules.
• In humans, aquaporins are present in distal and collecting tubules of kidney, brain astrocytes,
stomach parietal cells,…

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Diffusion through the Lipid Bilayer


The Diffusion of Water through Membranes
• A billion or so water molecules can pass—in single
file—through each channel every second.
• At the same time, H + ions are not able to
penetrate these open pores.
• Aquaporins are particularly prominent in cells, such
as those of a kidney tubule or plant root, where the
passage of water plays a crucial role in the tissue’s
physiologic activities.

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Diffusion through the Lipid Bilayer


The Diffusion of Water through Membranes
Ex: Aquaporins (AQP) in Kidney
o In the kidney, eight AQPs maintain
normal urine concentration
function, tissue development and
substance metabolism

o AQP-1 is located in proximal tubule,


descending thin limbs of Henle,
and vasa recta; AQP-2-6 are in the
collecting duct; AQP-7 and AQP-11
are expressed in proximal tubule.

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The Diffusion of Ions through Membranes


• Ion channels are pore-forming membrane proteins that allow ions
to pass through the channel pore.
• Most channels are specific (selective) for one ion.
• All channel proteins and many carrier proteins allow solutes to cross
the membrane only passively (“downhill”), a process called
passive transport, or facilitated diffusion.

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The Diffusion of Ions through Membranes


Classification by gating, mechanism of action:
Voltage-Gated, Ligand-gated, Mechanically-
Ion channels gated and Always open ion channels
The voltage-gated ion channels allow
permeation of only one type of ion while the
ligand-gated channels are less selective and
allow permeation of two or more types of ions
through the channel pore.

Voltage-gated Na+ and K+ channels are


responsible for the generation of action
potentials in neurons and skeletal muscle cells.
Ligand-gated ion channels are a group of
intrinsic transmembrane proteins that are
opened by the binding of a neurotransmitter.
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The Diffusion of Ions through Membranes

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The Diffusion of Ions through Membranes


§ The KcsA channel consists of four
subunits
§ Each subunit contain two
membrane-spanning helices (M1 and
M2) and a pore region (P) at the
extracellular end of the channel. P
consists of a short pore helix that extends
approximately one-third the width of the
channel and a nonhelical loop that forms
the lining of a narrow selectivity filter, so
named because of its role in allowing
only the passage of K + ions. Three-dimensional structure of the
bacterial KcsA channel and the selection
of K + ions
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The Diffusion of Ions through Membranes

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Facilitated Diffusion
• Facilitated diffusion is a type of passive transport
that uses specialized proteins, such as channel
proteins and carrier proteins, to help molecules move
across a cell membrane.
• Molecules can move down their concentration
gradient without requiring any energy input from the
cell.
• The plasma membrane is responsible for the
selective movements of substances.
• Examples of biological processes that entail
facilitated diffusion are glucose and amino acid
transport, gas transport, and ion transport. Facilitated
diffusion is important because it regulates what goes
in and what goes out of the cell.
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Facilitated Diffusion

Facilitated diffusion
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https://www.studyblue.com/notes/note/n/prokaryotic-cell-structure/deck/12149171

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Facilitated Diffusion

The kinetics of facilitated diffusion as compared to that of simple physical diffusion.


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Facilitated Diffusion
• GLUT4 transporter of glucose is an example of facilitated diffusion. Glucose
is the body’s primary source of direct energy, and most mammalian cells
contain a membrane protein that facilitates the diffusion of glucose from
the bloodstream into the cell.

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Active Transport
• Active transport is a kind of cellular
transport where substances move
against a concentration gradient
“uphill”
• Require the expenditure of energy
(as hydrolysis ATP), and the
assistance of membrane proteins
(integral membrane proteins), such
as carrier proteins.
• Proteins that carry out active
transport are often referred to as
“pumps” or “carrier proteins”.
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Active Transport
Primary Active Transport: Coupling Transport to ATP Hydrolysis
• Na+/K+-ATPase is an enzyme and ion pump that is one of the most important trans-
membrane proteins found in all animal cells.
• The two ions are transported through the sodium–potassium pump (need ATP
hydrolysis)
• Powered by ATP, the pump moves sodium and potassium ions in opposite
directions, each against its concentration gradient.
• In a single cycle of the pump, three sodium ions are extruded from and two
potassium ions are imported into the cell.

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Active Transport
Other Primary Ion Transport Systems
• The calcium pump
is present in the
membranes of the
endoplasmic
reticulum, where it
actively transports
calcium ions out of
the cytosol into the
lumen of this
organelle.

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Active Transport
Active
Other Primary IonTransport
Transport Systems

Control of acid secretion in the stomach

The epithelial lining of the stomach also contains a P-type pump, the H + /K + -ATPase, which secretes a solution of
concentrated acid (up to 0.16 N HCl) into the stomach chamber. In the resting state, these pump molecules are situated in
cytoplasmic membranes of the parietal cells of the stomach lining and are nonfunctional. When food enters the stomach, a
hormonal message is transmitted to the parietal cells that causes the pump-containing
membranes to move to the apical cell surface, where they fuse with the plasma membrane and begin secreting acid 40

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Secondary Active Transport

o Cotransporters drive the transport of different ion species in the same direction
using the downhill transport of one ion (ion 2) to fuel the uphill transport of the
other (ion 3).
o Exchangers promote the transport of ion species in opposite directions using
the electrochemical gradient of one ion (ion 2) to drive the other (ion 4). 41
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Active Transport
Secondary Active Transport (or Cotransporter): Coupling Transport to Existing Ion Gradients

o Co-transporter: no direct coupling of ATP; instead,


the electrochemical potential difference created
by pumping ions in or out of the cell is used.
o The establishment of concentration gradients,
such as those of Na+, K+, and H+, provides a
means by which free energy can be stored in a
cell. The potential energy stored in ionic gradients
is utilized by a cell in various ways to perform
work, including the transport of other solutes.
o The two main forms of this are antiport and Secondary transport: the use of
symport. energy stored in an ionic gradient

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Symport
• The transport of two different molecules or ions in the same direction
through a membrane using a common carrier mechanism.

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Symport

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Antiport
• A mechanism for the coupled transport of two different molecules or
ions through a membrane in opposite directions

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Primary active transport vs. Secondary active transport


Primary active transport Secondary active transport
(Direct active transport) (Coupled transport or cotransport)
Direct coupling of ATP No direct coupling of ATP
Energy used: Energy used:
Metabolic energy (ATP) Electrochemical gradient
Redox energy
Photon energy
Membrane protein transporter (ion pumps, ion channels, Cotransporters:
ATPases): Antiporters
P-type ATPase, e.g. sodium-potassium pump, calcium Symporters
pump, proton pump
F-ATPase, e.g. mitochondrial ATP synthase, chloroplast ATP
synthase
V-ATPase, i.e. vacuolar ATPase
ATP-binding cassette transporter: e.g. MDR, CFTR
Examples: Example:
Active transport using ATP via sodium-potassium pump to Active transport of a second substrate while another ion,
move 3 Na+ ions out while moving 2 K+ ions into the cell typically Na+, K+, or H+ ions, move down the concentration
Active transport using Redox energy (of NADH) to generate gradient
a proton gradient in the inner mitochondrial membrane
Active transport using photon energy (light) to generate a
proton gradient during photosynthesis

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Active Transport

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Endocytosis and Exocytosis


• Endocytosis is a process in which a cell
internalizes non-particulate materials such as
proteins by engulfing them in an energy-dependent
manner è Absorption into the cell
- Phagocytosis (cell eating)
- Pinocytosis (cell drinking)
- Receptor-mediated endocytosis-specific particles,
recognition
• Exocytosis is the process using energy to direct
contents of secretory vesicles of out the cells and
pour into extracellular regions è Secretion outside
the cell
- Non Ca2+ triggered-constitutive secretion
- Ca2+ triggered-constitutive secretion 48

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Endocytosis

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Exocytosis

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Bulk Transport: Many large molecules are moved at the same time. 51

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Summary

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Membrane permeability in acids and bases


Ionization and permeability

If a change in pH
should than cause
that substance to
The ionization of a become relatively
given substance, in non-ionized, it will
turn, is influenced by then pass more
the pH of its freely across the
environment; if a cell membrane
substance exists in along its
The permeability of concentration
an ionized state, its
the cell membrane to gradient
passage across the
a given moiety is cell membrane will
critically determined be considerable
by the ionization of hindered
that substance 53

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Membrane permeability in acids and bases


o Weak acids and bases constitute a class of
pharmacologically important substances
o At physiological pH most weak acids are
anions, A−, while their neutral form, AH,
is much more membrane-permeable.
o Consequently, proton-transfer reactions in
the immediate membrane vicinity play an
important role in the permeation process.
o Several steps may be occurred: 1), the
diffusion of A− to the membrane; 2), proton
uptake; 3), permeation of AH across the
membrane; 4), dissociation; and 5),
diffusion of A− into the bulk.
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Membrane permeability in acids and bases

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Filtration

Kidneys are the biological filters that filter out the toxins
from the body with urine and retain & reabsorb the
essential nutrients by glomerular filtration.

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Filtration

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Kidney: Filtration, ultrafiltration & selective reabsorption

o As fluid moves along the nephron,


selective reabsorption occurs.
o Substances are reabsorbed back
into the tissue fluid and blood
capillaries surrounding the
nephron tubule
o The final product is urine
o This passes into the pelvis and
down the ureter to the bladder

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Kidney: Filtration, ultrafiltration & selective reabsorption

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Kidney: Filtration, ultrafiltration & selective reabsorption

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Kidney: Filtration, ultrafiltration & selective reabsorption


Filtration pressure is the net pressure
forcing the fluid through the glomerular
membrane equals to the glomerular
pressure minus sum of glomerular
colloidal osmotic pressure and
capsular pressure.

E.g, If Glomerular Hydrostatic


Pressure = 55 mm Hg, Colloidal
Osmotic Pressure in glomerulus = 30
mm Hg and capsular pressure
(Bowman’s capsule Hydrostatic
Pressure) = 15 mm Hg. Then, the
Filtration pressure = 55-(30+15) = 10
mm Hg. 61

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Kidney: Filtration, ultrafiltration & selective reabsorption

What is filtered out of the What is left in the capillary?


blood? Blood cells
• Water Proteins
• Aa • This makes the blood have a low
• Glucose (very negative) water potential
• Urea which ensures some fluid is
• Inorganic ions (sodium, retained in the blood
chloride, potassium) • The very low water potential of
the blood in the capillaries helps
to reabsorb water at a later stage

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Selective reabsorption
• Most reabsorption occurs from the proximal convoluted tubule (ống
lượn gần)
• All glucose and amino acids, some salts and some water are
reabsorbed
• Sodium ion concentration is reduced as Sodium-potassium pumps
remove sodium ions from the cells lining the proximal convoluted tubule
• Sodium ions transported into the cell with glucose or amino acids by
facilitated diffusion
• Reabsorption of salts, glucose and amino acids reduces the water
potential in the cells (makes it more negative) and increases the water
potential in the tubule fluid (towards zero)- this means water will enter
the cells from the tubule fluid and then be reabsorbed into the blood by
osmosis
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Circulatory system

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• How our circulatory system has evolved


• How blood flow in our system
• What happens in my body when you get a cut, scrape, or puncture?
• What is blood?
• Blood is the fluid which flows in blood vessels
• It transports substances like digested food from the small intestine to
the other parts of the body.
• How does oxygen get into the bloodstream?
• It carries oxygen from the lungs to the cells of the body.
• It also transports waste for removal from the body.

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Circulatory system

è The major components of our circulation system include the heart (pump),
blood vessels (pipes), and various blood cells (carriers).
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Blood

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Blood vessels
• During inhalation a fresh supply of oxygen fills the
lungs >>> Oxygen has to be transported to the
rest of the body.
• the blood picks up the waste materials including
carbon dioxide from the cells. This blood has to
go back to the heart for transport to the lungs for
removal of carbon dioxide
• Two types of blood vessels, arteries and veins are
present in the body.

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Vascular circulation
Mammals (including humans) utilize a
double circulatory system (2 loops):
Small circulation: One circuit links the
heart and lungs
Large circulation: The other circuit links
the heart with the rest of the body

The certain circulation of blood flow is


controlled by heart contraction, vascular
wall elasticity, heart and vascular valves.

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Heart Structure

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Cardiac cycle: Systole - Diastole


• Diastole (tâm trương) and systole (tâm thu) are two
phases of the cardiac cycle.
• Cardiac cycle events can be divided into diastole
(tâm trương) and systole (tâm thu).
• Diastole represents ventricular filling, and systole
represents ventricular contraction/ejection.
• Systole and diastole occur in both the right and left
heart, though with very different pressures . They
occur as the heart beats, pumping blood through a
system of blood vessels that carry blood to every part
of the body.
• Systole occurs when the heart contracts to pump
blood out, and diastole occurs when the heart relaxes
after contraction

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Cardiac cycle: Systole - Diastole

Atrium systole (0,1s) - Atrium diastole (0,7s)


Ventricular systole (0,3s) = Pressure rise phase + Ejection phase - 74
Ventricular diastole (0,5s)

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RESPIRATION:
Transport of Oxygen and Carbon Dioxide

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Respiration

• Respiration is the process through which living organisms take in oxygen and
give out carbon dioxide to release energy.
• Respiration is a major and vital process of gas exchange.
• The transport of gases during respiration, both oxygen and carbon dioxide are
carried out by the blood cells.
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Respiration in human beings

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Gas exchange in the lungs

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How are O2 and CO2 transported in human beings?

Transport of oxygen:
The oxygen molecule can bind to the
haemoglobin molecules easily. One molecule of
haemoglobin binds four molecules of oxygen.
Haemoglobin present in the blood takes up the
oxygen from the air in the lungs. It carries the
oxygen to tissues which are deficient in oxygen
before releasing it.

Transport of carbon dioxide:


CO2 is more soluble in water. Therefore, it is
mostly transported from body tissues in the
dissolved form in our blood plasma to lungs in
the form of carboxyhemoglobin. Here it diffuses
from blood to air in the lungs.

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Digestion, Absorption, and Transport


in Digestive System
How the body uses food?
• The breakdown of complex macromolecules in
foods to absorbable components is
accomplished by the digestive system.
• These components are processed by cells
throughout the body into energy or are used as
building blocks.
• The digestive system is composed of the mouth,
pharynx, esophagus, stomach, small intestine,
large intestine (or colon), rectum, and anus.
• There are four steps in the digestion process:
ingestion, the breakdown of food, nutrient
absorption, and elimination of indigestible food

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Digestion, Absorption, and Transport


in Digestive System

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Digestion, Absorption, and Transport


in Digestive System

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Digestion, Absorption, and Transport


in Digestive System

Absorption of different nutrients

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Digestion, Absorption, and Transport


in Digestive System

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Digestion, Absorption, and Transport


in Digestive System

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Digestion, Absorption, and Transport


in Digestive System

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Digestion, Absorption, and Transport


in Digestive System

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Human excretory system


o Human excretory removes excess
water, urea, Co2, and other wastes
from our blood
o Kinney – filter out excess water and
urea
o Lungs – filter out CO2 from blood
o Skin – excretes water (sweat) which
contains some trace chemical wasters
including urea

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Excretory system in humans


• Human excretory system includes organs that
facilitate the removal of nitrogenous wastes from
the body.
• The main excretory organs include kidney, ureter
(niệu quản), urinary bladder (bàng quang tiết
niệu) and urethra (niệu đạo).
• Kidneys filter the blood and urine is the filtrate
obtained.
• Urine passes to the urinary bladder via ureter and
is expelled out of the body. This is known as
micturition (sự tiểu).
• Kidneys also regulate the osmotic pressure of a
mammal’s blood through excessive purification
and filtration.
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Excretion in human beings

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