Introduction to Introduction to GENERAL PHYSIOLOGYGENERAL PHYSIOLOGY

andandCELL PHYSIOLOGYCELL PHYSIOLOGY

Lecture No. 1Lecture No. 1

General PhysiologyGeneral Physiology

Objectives:Objectives: This presentation features the basic This presentation features the basic

physiologic concepts you need to explain physiologic concepts you need to explain scientific basis of disease with emphasis on scientific basis of disease with emphasis on specific cause-and-effect mechanisms.specific cause-and-effect mechanisms.

Through these basic concepts you should Through these basic concepts you should be able to apply scientific information to the be able to apply scientific information to the clinical reasoning process.clinical reasoning process.

What is General Physiology?What is General Physiology?

It is a branch of biological science which deals It is a branch of biological science which deals with the study of how the human body functions.with the study of how the human body functions.

All cells, tissues and organs perform their All cells, tissues and organs perform their functions in concert with each other as smoothly functions in concert with each other as smoothly operating systems.operating systems.

Knowledge of the mechanisms in which these Knowledge of the mechanisms in which these systems work have been obtained experimentally systems work have been obtained experimentally through applications of the scientific method.through applications of the scientific method.

Let’s start with Homeostasis!Let’s start with Homeostasis! Homeostasis is the process by which an organism Homeostasis is the process by which an organism

maintains the composition of the extracellular fluid (ECF) maintains the composition of the extracellular fluid (ECF) and intracellular fluid (ICF) in a steady-state condition.and intracellular fluid (ICF) in a steady-state condition.

ECF consists of the blood plasma and interstitial fluid. ECF consists of the blood plasma and interstitial fluid. The composition of the ECF is maintained by the The composition of the ECF is maintained by the cardiovascular, pulmonary, renal, gastrointestinal, cardiovascular, pulmonary, renal, gastrointestinal, endocrine, and nervous systems acting in coordinated endocrine, and nervous systems acting in coordinated fashion.fashion.

ICF’s composition is maintained by the cell membrane, ICF’s composition is maintained by the cell membrane, which mediates the transport of material between which mediates the transport of material between between the ICF and ECF by diffusion, osmosis, and between the ICF and ECF by diffusion, osmosis, and active transport.active transport.

How does homoestasis take How does homoestasis take place?place?

Blood Calcium levelsBlood Calcium levels

Blood levels of calcium are held constant at set Blood levels of calcium are held constant at set point by hormones. point by hormones.

Normal value of calcium: 9-11 mg%Normal value of calcium: 9-11 mg% Parathyroid hormone or parathormone is one Parathyroid hormone or parathormone is one

hormone that helps raise the blood calcium hormone that helps raise the blood calcium concentration. concentration.

Thyrocalcitonin – acts to reduce the blood level of Thyrocalcitonin – acts to reduce the blood level of calcium and to inhibit bone resorption. It also calcium and to inhibit bone resorption. It also promotes the excretion of phosphate, sodium and promotes the excretion of phosphate, sodium and calcium by decreasing their reabsorption in kidney calcium by decreasing their reabsorption in kidney tubules. tubules.

Temperature ControlTemperature Control In homeostasis, the critical concept describing the body’s In homeostasis, the critical concept describing the body’s

response to any deviation from some particular setpoint response to any deviation from some particular setpoint (such as temperature rising when exercising), which results (such as temperature rising when exercising), which results the activation of mechanisms to oppose that deviation the activation of mechanisms to oppose that deviation (return temperature toward normal), is known as negative (return temperature toward normal), is known as negative feedback.feedback.

In this kind of homeostasis, the setpoint is analogous to the In this kind of homeostasis, the setpoint is analogous to the house thermostat setting that operates to regulate the house thermostat setting that operates to regulate the temperature in the house.temperature in the house.

The sequence that best reflects how the body maintains The sequence that best reflects how the body maintains homeostasis (example, during a fever):homeostasis (example, during a fever):1. sensor activated1. sensor activated

2. integrating center process2. integrating center process 3. effector activated3. effector activated 4. negative feedback loops activated4. negative feedback loops activated 5. return to setpoint5. return to setpoint

Homeostasis & Feedback ControlHomeostasis & Feedback Control

Homeostasis refers to the dynamic constancy of Homeostasis refers to the dynamic constancy of the internal environmentthe internal environment

Homeostasis is maintained by mechanisms that Homeostasis is maintained by mechanisms that act through negative feedback loops.act through negative feedback loops.

A negative feedback loop requires a sensor that A negative feedback loop requires a sensor that can detect a change in the environment and an can detect a change in the environment and an effector that can be activated by the sensoreffector that can be activated by the sensor

The effector acts to cause changes in the internal The effector acts to cause changes in the internal environment that compensates the initial environment that compensates the initial deviations that were detected by the sensor.deviations that were detected by the sensor.

Negative FeedbackNegative Feedback Neurons in the hypothalamus secrete Neurons in the hypothalamus secrete

thyroid releasing hormone (TRH) which thyroid releasing hormone (TRH) which stimulates cells in the anterior pituitary to stimulates cells in the anterior pituitary to secrete TSHsecrete TSH

TSH binds to receptors on epithelial cells in TSH binds to receptors on epithelial cells in the thyroid gland, stimulating synthesis and the thyroid gland, stimulating synthesis and secretion of thyroid hormones, which affect secretion of thyroid hormones, which affect probably all cells of the bodyprobably all cells of the body

When blood concentrations of thyroid When blood concentrations of thyroid hormones increase above a certain hormones increase above a certain threshold, TRH secreting neurons in the threshold, TRH secreting neurons in the hypothalamus as inhibited and stop hypothalamus as inhibited and stop secreting TRH. secreting TRH.

This is an example of “negative feedbackThis is an example of “negative feedback””

What is the Donnan Equilibrium?What is the Donnan Equilibrium?

When two solutions containing charged particles When two solutions containing charged particles (ions) are separated by a membrane that is (ions) are separated by a membrane that is permeable to some of the ions and not to others, a permeable to some of the ions and not to others, a Donnan equilibrium will be established.Donnan equilibrium will be established.

A Donnan equilibrium is an example of an A Donnan equilibrium is an example of an electrochemical equilibrium, because the electrical electrochemical equilibrium, because the electrical and chemical energies on either side of the and chemical energies on either side of the membrane are equal and opposite to each other.membrane are equal and opposite to each other.

What are some of the apparatus What are some of the apparatus used in Physiology? used in Physiology?

KymographKymograph

POLYGRAPHPOLYGRAPH

MRI & SPIROMETERMRI & SPIROMETER

MRI & SpirometerMRI & Spirometer Magnetic Resonance Imaging (MRI) – the new technique Magnetic Resonance Imaging (MRI) – the new technique

of visualizing the brain creates excellent images by of visualizing the brain creates excellent images by detecting emitted radio wave signals released from detecting emitted radio wave signals released from stimulated protons aligned in the tissues.stimulated protons aligned in the tissues.

Positron-Emission Tomography (PET) – a computerized Positron-Emission Tomography (PET) – a computerized radiographic technique used to examine the metabolic radiographic technique used to examine the metabolic activity of various body structures.activity of various body structures.

Computed Tomography (CT Scan) – visualizes how the Computed Tomography (CT Scan) – visualizes how the brain utilizes complex manipulation of x-ray absorption data brain utilizes complex manipulation of x-ray absorption data obtained from tissues of different densities.obtained from tissues of different densities.

Spirometer – used to measure and record the volume of Spirometer – used to measure and record the volume of inhaled and exhaled air, used to assess pulmonary inhaled and exhaled air, used to assess pulmonary function.function.

CT SCANCT SCAN

COULTER COUNTERCOULTER COUNTER

Coulter Counter, Oscilloscope & Coulter Counter, Oscilloscope & ErgographErgograph

Coulter CounterCoulter Counter is a trademark for an is a trademark for an electric device that rapidly identifies, sorts, electric device that rapidly identifies, sorts, and counts the various kinds of cells present and counts the various kinds of cells present in a small specimen of blood.in a small specimen of blood.

OscilloscopeOscilloscope – used in cardiography, used – used in cardiography, used to display graphic representation of beam of to display graphic representation of beam of electrons on the screen.electrons on the screen.

ErgographErgograph – a device used to measure – a device used to measure contraction of specific muscles or muscle contraction of specific muscles or muscle groups.groups.

OSCILLOSCOPE & ERGOGRAPHOSCILLOSCOPE & ERGOGRAPH

Blood Pressure MachineBlood Pressure Machine

HEMOCYTOMETERHEMOCYTOMETER

HEMODIALYSIS MACHINEHEMODIALYSIS MACHINE HemodialysisHemodialysis is a is a

procedure in which procedure in which impurities or wastes are impurities or wastes are removed from the blood, removed from the blood, used in treating renal used in treating renal failure and various toxic failure and various toxic conditions.conditions.

The patient’s blood is The patient’s blood is shunted from the body shunted from the body through a machine for through a machine for diffusion and diffusion and ultrafiltration and then ultrafiltration and then returned to the patient’s returned to the patient’s blood circulation.blood circulation.

pH METER & URINOMETERpH METER & URINOMETER

STETHOSCOPE & PULSE WATCHSTETHOSCOPE & PULSE WATCH

AUDIOMETER & TUNING FORKAUDIOMETER & TUNING FORK

Audiometer, Tuning Fork & Rubber Audiometer, Tuning Fork & Rubber malletmallet

Audiometer an electric device used to test Audiometer an electric device used to test the sensitivity of the sense of hearing.the sensitivity of the sense of hearing.

Tuning fork – a small metal instrument Tuning fork – a small metal instrument consisting of a stem and two prongs that consisting of a stem and two prongs that produces a constant pitch when either prong produces a constant pitch when either prong is struck. It is used in auditory tests of nerve is struck. It is used in auditory tests of nerve function and of air and bone conduction.function and of air and bone conduction.

Rubber hammer or mallet – used in patelllar Rubber hammer or mallet – used in patelllar reflex or in ankle jerk reflex reflex or in ankle jerk reflex

CELL PHYSIOLOGYCELL PHYSIOLOGY

The CellThe Cell The cell is the basic unit of structure and function The cell is the basic unit of structure and function

in the body. Many of the functions of cells are in the body. Many of the functions of cells are performed by particular subcellular structures performed by particular subcellular structures called organelles. called organelles.

The human body contains about 100 trillion cells, The human body contains about 100 trillion cells, each of which is a living structure. Several each of which is a living structure. Several hundred basic types of cells exist in the body, Yet hundred basic types of cells exist in the body, Yet despite the difference between cells, they will have despite the difference between cells, they will have some functions in common, like their ability to live, some functions in common, like their ability to live, grow and reproduce. grow and reproduce.

Some show characteristics of metabolism, Some show characteristics of metabolism, irritability and even movement or locomotionirritability and even movement or locomotion. .

Each is specially adapted to perform one particular Each is specially adapted to perform one particular functionfunction

Functions of organellesFunctions of organelles

Mitochondria as Mitochondria as the powerhouse the powerhouse of the cell, have of the cell, have membranes membranes folded into cristae folded into cristae with matrix with matrix material involved material involved in ATP production in ATP production (energy).(energy).

Golgi complexGolgi complex The important role of the The important role of the

Golgi complex is to make Golgi complex is to make certain the plasma certain the plasma membrane proteins reach membrane proteins reach their destination. their destination.

The orientation of the The orientation of the protein is maintained so that protein is maintained so that the region destined to the region destined to project outside the cell ends project outside the cell ends up in that place.up in that place.

In order to do this, it must In order to do this, it must be placed so that it faces be placed so that it faces inside the vesicle.inside the vesicle.

Secretory Pathway in a CellSecretory Pathway in a Cell1.Nuclear membrane1.Nuclear membrane2. Nuclear pore2. Nuclear pore3. rER3. rER4. sER4. sER5. Ribosomes 5. Ribosomes

attached to rERattached to rER6. Macromolecules6. Macromolecules7. Transport vesicles7. Transport vesicles8. Golgi apparatus8. Golgi apparatus9. Cis face of Golgi9. Cis face of Golgi10. Trans face of 10. Trans face of

GolgiGolgi11. Cisternae of Golgi 11. Cisternae of Golgi

apparatusapparatus

Endoplasmic reticulumEndoplasmic reticulum rERrER – consists of – consists of

flattened sacks of flattened sacks of cisternae studded with cisternae studded with ribosomes for the ribosomes for the synthesis of proteins synthesis of proteins destined for secretiondestined for secretion

sERsER- consists of an - consists of an anastomosing network of anastomosing network of interconnected citernae interconnected citernae and tubules. It functions and tubules. It functions in glycogen breakdown, in glycogen breakdown, synthesis of cholesterol synthesis of cholesterol and phospholipids and and phospholipids and serves to detoxify drugs serves to detoxify drugs and poisonsand poisons

LysosomesLysosomes Lysosomes are membrane- Lysosomes are membrane-

bounded organelles bounded organelles containing hydrolytic containing hydrolytic enzymes. enzymes.

They have several functions in They have several functions in cell physiology. They degrade cell physiology. They degrade phagocytized foreign phagocytized foreign materials, lipid aggregates materials, lipid aggregates and glycogen granules, and glycogen granules, responsible also in tissue responsible also in tissue degradation during degradation during regression, and are abundant regression, and are abundant in macrophages and in in macrophages and in leukocytes.leukocytes.

MicrofilamentsMicrofilamentsThis is a This is a

flourescence flourescence digital image of digital image of

a fibroblast a fibroblast showing actin showing actin cytoskeletal cytoskeletal

networknetwork..

MicrofilamentsMicrofilaments Microfilaments are actin-rich filamentous Microfilaments are actin-rich filamentous

structures.structures. In muscle cells, they provide a dynamic framework In muscle cells, they provide a dynamic framework

for the cell permitting extensions of pseudopodia, for the cell permitting extensions of pseudopodia, endocytosis of extracellular materials, and cell endocytosis of extracellular materials, and cell motilitymotility

They are especially abundant in muscle cells They are especially abundant in muscle cells where they are essential component of the thin where they are essential component of the thin filaments.filaments.

Intermediate filaments are fibrous structures Intermediate filaments are fibrous structures consisting of several proteins including desmin, consisting of several proteins including desmin, vimentin, and keratin.vimentin, and keratin.

Microtubules are cytoskeletal elements in Microtubules are cytoskeletal elements in certain forms of cell movement and is an certain forms of cell movement and is an essential component of the mitotic spindle, essential component of the mitotic spindle, centrioles, basal bodies, cilia, and flagella.centrioles, basal bodies, cilia, and flagella.

They attach to chromosomes at the They attach to chromosomes at the kinetochore and are essential for mitotic kinetochore and are essential for mitotic separation of chromosomes.separation of chromosomes.

The NucleusThe Nucleus This is found in all cells This is found in all cells

except in mature rbc’s and except in mature rbc’s and blood platelets.blood platelets.

Functions: Functions: - Contains chromosomes - Contains chromosomes

which consist of genes which consist of genes (bearers of hereditary (bearers of hereditary characteristics)characteristics)

- Concerned with the - Concerned with the growth and reproduction of growth and reproduction of cellscells

Parts: Nuclear envelope, Parts: Nuclear envelope, nuclear pores, chromatin nuclear pores, chromatin materials, nucleolus, materials, nucleolus, nuclear sap or karyoplasmnuclear sap or karyoplasm

Heterochromatin – forms the condensed or coiled parts of the chromosomes (metabolically inert)Euchromatin – forms the dispersed or extended parts of the chromosomes (metabolically active)

The Genetic CodeThe Genetic Code The genetic code is based on the The genetic code is based on the

structure of DNA and is expressed structure of DNA and is expressed through the structure and function through the structure and function of RNA. of RNA.

DNA and RNA are composed of DNA and RNA are composed of subunits called nucleotides, and subunits called nucleotides, and together these molecules are together these molecules are known as nucleic acids. known as nucleic acids.

The genetic code is based on the The genetic code is based on the sequences of DNA nucleotides, sequences of DNA nucleotides, which serve to direct the synthesis which serve to direct the synthesis of RNA molecules. of RNA molecules.

It is through the RNA-directed It is through the RNA-directed synthesis of proteins that the synthesis of proteins that the genetic code is expressed. genetic code is expressed.

NucleotidesNucleotides Nucleotides are the Nucleotides are the

repeating units of repeating units of nucleic acids.nucleic acids.

They are made up of They are made up of nitrogenous basenitrogenous base (pyrimidine and (pyrimidine and purine), purine), pentose pentose sugarsugar and and phosphate groupphosphate group..

Types of RNATypes of RNA

Types of RNA in a GeneTypes of RNA in a Gene

Ribosomal RNA (rRNA)Ribosomal RNA (rRNA) In the cytoplasm, In the cytoplasm,

rRNA and protein rRNA and protein combine to form a combine to form a nucleoprotein called nucleoprotein called a ribosome. a ribosome.

The ribosome serves The ribosome serves as the site and as the site and carries the enzymes carries the enzymes necessary for protein necessary for protein synthesis synthesis

Types of RNATypes of RNA RNA: tRNA, mRNA, rRNARNA: tRNA, mRNA, rRNA

tRNa is characterized by bending tRNa is characterized by bending on itself to form a cloverleaf on itself to form a cloverleaf structure that twists further into an structure that twists further into an upside down “L” shape.upside down “L” shape.

In order for a gene to be expressed, In order for a gene to be expressed, it first must be used as a guide, or it first must be used as a guide, or template, in the production of a template, in the production of a complementary strand of mRNA.complementary strand of mRNA.

This mRNA is then itself used as a This mRNA is then itself used as a guide to produce a particular type guide to produce a particular type of protein whose sequence of of protein whose sequence of amino acids is determined by the amino acids is determined by the sequence of base triplets (codons) sequence of base triplets (codons) in the mRNAin the mRNA

Translation and TranscriptionTranslation and Transcription Translation is Translation is

best defined as best defined as the synthesis of the synthesis of specific specific proteins from proteins from the mRNA base the mRNA base sequence codesequence code

Transcription is Transcription is the synthesis of the synthesis of RNA molecules RNA molecules from DNA from DNA

History of the Plasma MembraneHistory of the Plasma Membrane 1665: Robert Hooke 1665: Robert Hooke 1895: Charles Overton - composed of lipids 1895: Charles Overton - composed of lipids 1900-1920’s: must be a phospholipid 1900-1920’s: must be a phospholipid 1925: E. Gorter and G. Grendel - 1925: E. Gorter and G. Grendel -

phospholipid phospholipid bilayerbilayer 1935: J.R. Danielli and H. Davson – proteins 1935: J.R. Danielli and H. Davson – proteins

also part, proposed the also part, proposed the Sandwich ModelSandwich Model 1950’s: J.D. Robertson – proposed the 1950’s: J.D. Robertson – proposed the Unit Unit

Membrane ModelMembrane Model 1972: S.J. Singer and G.L. Nicolson – 1972: S.J. Singer and G.L. Nicolson –

proposed proposed Fluid Mosaic ModelFluid Mosaic Model

Plasma Membrane is made of Plasma Membrane is made of PhospholipidsPhospholipids

Gorter + Grendel Gorter + Grendel – Red Blood Cells analyzedRed Blood Cells analyzed– Enough for Phospholipid bilayerEnough for Phospholipid bilayer– Polar heads face out and Polar heads face out and

Nonpolar tails face in Nonpolar tails face in– Does not explain why some Does not explain why some

nonlipids are permeable nonlipids are permeable

Plasma Membrane ModelsPlasma Membrane Models

Sandwich ModelSandwich Model(Danielli + Davson)(Danielli + Davson)2 layers of globular proteins with phospholipid 2 layers of globular proteins with phospholipid inside to make a layer and then join 2 layers inside to make a layer and then join 2 layers together to make a channel for molecules totogether to make a channel for molecules to passpass

Unit Membrane Model Unit Membrane Model (Robertson)(Robertson)Outer layer of protein with phospholipid bilayer Outer layer of protein with phospholipid bilayer inside, believed all cells same composition, inside, believed all cells same composition, does not explain how some molecules pass does not explain how some molecules pass through or the use of proteins with nonpolar through or the use of proteins with nonpolar parts, used transmission electron microscopyparts, used transmission electron microscopy

Fluid Mosaic Model Fluid Mosaic Model (Singer + Nicolson)(Singer + Nicolson)Phospholipid bilayer with proteins partially or Phospholipid bilayer with proteins partially or fully imbedded, electron micrographs of freeze-fully imbedded, electron micrographs of freeze-fractured membranefractured membrane

Which membrane model is correct?Which membrane model is correct?

1) Rapidly freeze specimen1) Rapidly freeze specimen

2) Use special knife to cut membrane in half2) Use special knife to cut membrane in half

3) Apply a carbon + platinum coating to the surface3) Apply a carbon + platinum coating to the surface

4) Use scanning electron microscope to see the surface4) Use scanning electron microscope to see the surface

According to the electron micrograph which membrane model is correct?According to the electron micrograph which membrane model is correct?

Why?Why?

Fluid-Mosaic ModelFluid-Mosaic Model

Fluid-Mosaic ModelFluid-Mosaic Model FluidFluid – the plasma membrane is the consistency of olive oil at body – the plasma membrane is the consistency of olive oil at body

temperature, due to unsaturated phospholipids. (cells differ in the temperature, due to unsaturated phospholipids. (cells differ in the amount of unsaturated to saturated fatty acid tails) amount of unsaturated to saturated fatty acid tails)

Most of the lipids and some proteins drift laterally on either side. Most of the lipids and some proteins drift laterally on either side. Phospholipids do not switch from one layer to the next.Phospholipids do not switch from one layer to the next.

Cholesterol affects fluidity: at body temperature it lessens fluidity by Cholesterol affects fluidity: at body temperature it lessens fluidity by restraining the movement of phospholipids, at colder temperatures it restraining the movement of phospholipids, at colder temperatures it adds fluidity by not allowing phospholipids to pack close together.adds fluidity by not allowing phospholipids to pack close together.

MosaicMosaic – membrane proteins form a collage that differs on either – membrane proteins form a collage that differs on either side of the membrane and from cell to cell (greater than 50 types of side of the membrane and from cell to cell (greater than 50 types of proteins), proteins span the membrane with hydrophilic portions facing proteins), proteins span the membrane with hydrophilic portions facing out and hydrophobic portions facing in. Provides the functions of the out and hydrophobic portions facing in. Provides the functions of the membranemembrane

Structure of the Plasma MembraneStructure of the Plasma Membrane

Structure of the Plasma MembraneStructure of the Plasma Membrane

Phospholipid bilayerPhospholipid bilayer

PhospholipidPhospholipid– Hydrophilic headHydrophilic head– Hydrophobic tailsHydrophobic tails

CholesterolCholesterol

ProteinsProteins– Transmembrane/Transmembrane/

Intrinsic/Intrinsic/IntegralIntegral

– Peripheral/ExtrinsicPeripheral/Extrinsic

Cytoskeletal filamentsCytoskeletal filaments

Carbohydrate chainCarbohydrate chain

GlycoproteinsGlycoproteins

GlycolipidsGlycolipids

Proteins of the Plasma Membrane Proteins of the Plasma Membrane Provide 6 Membrane Functions:Provide 6 Membrane Functions:

1) 1) Transport ProteinsTransport Proteins

2) 2) Receptor ProteinsReceptor Proteins

3) 3) Enzymatic ProteinsEnzymatic Proteins

4) 4) Cell Recognition ProteinsCell Recognition Proteins

5) 5) Attachment ProteinsAttachment Proteins

6) 6) Intercellular Junction Intercellular Junction

ProteinsProteins

1)1) Transport ProteinsTransport Proteins

Channel ProteinsChannel Proteins – – channel for lipid channel for lipid insoluble molecules insoluble molecules and ions to pass freely and ions to pass freely throughthrough

Carrier ProteinsCarrier Proteins – bind – bind to a substance and to a substance and carry it across carry it across membrane, change membrane, change shape in processshape in process

2)2) Receptor ProteinsReceptor Proteins

– – Bind to chemical Bind to chemical messengers (Ex. messengers (Ex. hormones) which hormones) which sends a message into sends a message into the cell causing the cell causing cellular reactioncellular reaction

3)3) Enzymatic ProteinsEnzymatic Proteins

– – Carry out enzymatic Carry out enzymatic reactions right at the reactions right at the membrane when a membrane when a substrate binds to the substrate binds to the active siteactive site

4)4) Cell Recognition ProteinsCell Recognition Proteins

– – Glycoproteins (and Glycoproteins (and glycolipids) on glycolipids) on extracellular surface extracellular surface serve as ID tags serve as ID tags (which species, type of (which species, type of cell, individual). cell, individual). Carbohydrates are Carbohydrates are short branched chains short branched chains of less than 15 sugarsof less than 15 sugars

5)5) Attachment ProteinsAttachment Proteins

- Attach to cytoskeleton (to Attach to cytoskeleton (to maintain cell shape and stabilize maintain cell shape and stabilize proteins) and/or the extracellular proteins) and/or the extracellular matrix (integrins connect to matrix (integrins connect to both).both).

- Extracellular Matrix – protein Extracellular Matrix – protein fibers and carbohydrates fibers and carbohydrates secreted by cells and fills the secreted by cells and fills the spaces between cells and spaces between cells and supports cells in a tissue. supports cells in a tissue.

- Extracellular matrix can Extracellular matrix can influence activity inside the cell influence activity inside the cell and coordinate the behavior of and coordinate the behavior of all the cells in a tissue.all the cells in a tissue.

6)6) Intercellular Junction ProteinsIntercellular Junction Proteins

– – Bind cells togetherBind cells together

– Tight junctionsTight junctions

– Gap junctionsGap junctions

• Materials must move Materials must move in and out of the cell in and out of the cell through the plasma through the plasma membrane.membrane.

• Some materials Some materials move between the move between the phospholipids.phospholipids.

• Some materials Some materials move through the move through the proteins.proteins.

How do materials move into and How do materials move into and out of the cell?out of the cell?

Plasma Membrane TransportPlasma Membrane Transport

• Molecules move across the plasma Molecules move across the plasma membrane by:membrane by:

What are three types of What are three types of passive transport?passive transport?

1)1) DiffusionDiffusion

2)2) Facilitated DiffusionFacilitated Diffusion

3)3) OsmosisOsmosisATP energy is ATP energy is notnot

needed to move the needed to move the molecules through.molecules through.

Passive Transport 1: DiffusionPassive Transport 1: Diffusion

• Molecules can move directly Molecules can move directly through the phospholipids of the through the phospholipids of the plasma membraneplasma membrane

This is called …This is called …

What is Diffusion?What is Diffusion?

• Diffusion is the net Diffusion is the net movement of molecules movement of molecules from a high from a high concentration to a low concentration to a low concentration until concentration until equally distributed.equally distributed.

• Diffusion rate is related Diffusion rate is related to temperature, to temperature, pressure, state of matter, pressure, state of matter, size of concentration size of concentration gradient, and surface gradient, and surface area of membrane.area of membrane.

http://www.biologycorner.com/resources/diffusion-animated.gif

What molecules pass through the What molecules pass through the plasma membrane by diffusionplasma membrane by diffusion??

• Gases (oxygen, carbon Gases (oxygen, carbon dioxide)dioxide)

• Water molecules (rate Water molecules (rate slow due to polarity)slow due to polarity)

• Lipids (steroid Lipids (steroid hormones)hormones)

• Lipid soluble molecules Lipid soluble molecules (hydrocarbons, alcohols, (hydrocarbons, alcohols, some vitamins)some vitamins)

• Small noncharged Small noncharged molecules (NHmolecules (NH33))

Why is diffusion important to cells Why is diffusion important to cells and humans?and humans?

• Cell respirationCell respiration• Alveoli of lungsAlveoli of lungs• CapillariesCapillaries• Red Blood CellsRed Blood Cells• Medications: time-Medications: time-

release capsulesrelease capsules

Passive Transport 2Passive Transport 2: Facilitated : Facilitated DiffusionDiffusion

• Molecules can move through the Molecules can move through the plasma membrane with the aid of plasma membrane with the aid of transport proteinstransport proteins

This is called …This is called …

What is Facilitated Diffusion?What is Facilitated Diffusion?

• Facilitated diffusion Facilitated diffusion is the net movement is the net movement of molecules from a of molecules from a high concentration to high concentration to a low concentration a low concentration with the aid of with the aid of channel or carrier channel or carrier proteinsproteins..

What molecules move through the plasma What molecules move through the plasma membrane by facilitated diffusion?membrane by facilitated diffusion?

• IonsIons (Na(Na++, K, K++, Cl, Cl--))

• Sugars (Glucose)Sugars (Glucose)

• Amino AcidsAmino Acids

• Small water soluble Small water soluble moleculesmolecules

• Water (faster rate)Water (faster rate)

How do molecules move through the How do molecules move through the plasma membrane by facilitated diffusion?plasma membrane by facilitated diffusion?

• Channel and Carrier proteins are specific:Channel and Carrier proteins are specific:• Channel Proteins allow ions, small solutes, and water Channel Proteins allow ions, small solutes, and water

to passto pass• Carrier Proteins move glucose and amino acidsCarrier Proteins move glucose and amino acids• Facilitated diffusion is rate limited, by the number of Facilitated diffusion is rate limited, by the number of

proteins channels/carriers present in the membrane.proteins channels/carriers present in the membrane.

Specific Types of Facilitated Specific Types of Facilitated DiffusionDiffusion

Counter TransportCounter Transport – the transport – the transport of two substances at the same time of two substances at the same time in opposite directions, without ATP. in opposite directions, without ATP. Protein carriers are called Protein carriers are called AntiportsAntiports..

Co-transport Co-transport – the transport of – the transport of two substances at the same time in two substances at the same time in the same direction, without ATP. the same direction, without ATP. Protein carriers are called Protein carriers are called SymportsSymports..

Gated ChannelsGated Channels – receptors – receptors combined with channel proteins. combined with channel proteins. When a chemical messenger binds When a chemical messenger binds to a receptor, a gate opens to allow to a receptor, a gate opens to allow ions to flow through the channel. ions to flow through the channel.

Why is facilitated diffusion Why is facilitated diffusion important to cells and humans?important to cells and humans?

• Cells obtain food for Cells obtain food for cell respirationcell respiration

• Neurons Neurons communicatecommunicate

• Small intestine cells Small intestine cells transport food to transport food to bloodstreambloodstream

• Muscle cells contractMuscle cells contract

Passive Transport 3: OsmosisPassive Transport 3: Osmosis

• Water Molecules can move directly Water Molecules can move directly through the phospholipids of the through the phospholipids of the plasma membraneplasma membrane

This is called …This is called …

What is OsmosisWhat is Osmosis??

• Osmosis is the diffusion of water through a Osmosis is the diffusion of water through a semipermeable membrane. Water molecules bound semipermeable membrane. Water molecules bound to solutes cannot pass due to size, only unbound to solutes cannot pass due to size, only unbound molecules. Free water molecules collide, bump into molecules. Free water molecules collide, bump into the membrane, and pass through.the membrane, and pass through.

Osmosis in actionOsmosis in action• What will happen in the What will happen in the

U-tube if water freely U-tube if water freely moves through the moves through the membrane but glucose membrane but glucose can not pass?can not pass?

• Water moves from side with Water moves from side with high concentration of water to high concentration of water to side with lower concentration side with lower concentration of water. Movement stops of water. Movement stops when osmotic pressure when osmotic pressure equals hydrostatic pressure.equals hydrostatic pressure.

Why is osmosis important to cells Why is osmosis important to cells and humans?and humans?

• Cells remove water Cells remove water produced by cell produced by cell respiration.respiration.

• Large intestine cells Large intestine cells transport water to transport water to bloodstreambloodstream

• Kidney cells form Kidney cells form urineurine

Osmosis and TonicityOsmosis and Tonicity

Tonicity refers to the total solute Tonicity refers to the total solute concentration of the solution outside the concentration of the solution outside the cell.cell.

What are the three types of tonicity?What are the three types of tonicity?1)1) IsotonicIsotonic

2)2) HypotonicHypotonic

3)3) HypertonicHypertonic

IsotonicIsotonic Solutions that have the Solutions that have the samesame concentration of concentration of

solutes as the suspended cell.solutes as the suspended cell.

What will happen to a cell placed in an Isotonic What will happen to a cell placed in an Isotonic solution?solution?

The cell will have no net movement of water and The cell will have no net movement of water and will stay the same size.will stay the same size.

Ex. Blood plasma has high concentration of Ex. Blood plasma has high concentration of albumin molecules to make it isotonic to tissues.albumin molecules to make it isotonic to tissues.

HypotonicHypotonic Solutions that have a Solutions that have a lowerlower solute concentration solute concentration

than the suspended cell.than the suspended cell.

What will happen to a cell placed in a Hypotonic What will happen to a cell placed in a Hypotonic solution?solution?

The cell will gain water and swell.The cell will gain water and swell. If the cell bursts, then we call this lysis. (Red blood If the cell bursts, then we call this lysis. (Red blood

cells = hemolysis)cells = hemolysis) In plant cells with rigid cell walls, this creates In plant cells with rigid cell walls, this creates

turgor pressure.turgor pressure.

HypertonicHypertonic Solutions that have a Solutions that have a higherhigher solute concentration solute concentration

than a suspended cell.than a suspended cell.

What will happen to a cell placed in a Hypertonic What will happen to a cell placed in a Hypertonic solution?solution?

The cell will lose water and shrink. (Red blood The cell will lose water and shrink. (Red blood cells = crenation)cells = crenation)

In plant cells, the central vacuole will shrink and In plant cells, the central vacuole will shrink and the plasma membrane will pull away from the cell the plasma membrane will pull away from the cell wall causing the cytoplasm to shrink called wall causing the cytoplasm to shrink called plasmolysis.plasmolysis.

Review: Passive TransportReview: Passive Transport

• DiffusionDiffusion – O – O22 moves in and CO moves in and CO22 moves out moves out during cell respirationduring cell respiration

• Facilitated DiffusionFacilitated Diffusion – glucose and amino – glucose and amino acids enter cell for cell respirationacids enter cell for cell respiration

• OsmosisOsmosis – cell removal or addition of water – cell removal or addition of water

Review TonicityReview Tonicity What will happen to a red blood cell in a What will happen to a red blood cell in a

hypertonic solution?hypertonic solution? What will happen to a red blood cell in an What will happen to a red blood cell in an

isotonic solution?isotonic solution? What will happen to a red blood cell in a What will happen to a red blood cell in a

hypotonic solution?hypotonic solution?

1) Active Transport1) Active Transport2) Exocytosis2) Exocytosis3) Endocytosis3) Endocytosis

– PhagocytosisPhagocytosis– PinocytosisPinocytosis– Receptor-Mediated Receptor-Mediated

endocytosisendocytosis

What are three types of What are three types of Active transport?Active transport?

ATP energy is ATP energy is requiredrequired to move the to move the molecules through.molecules through.

Active TransportActive Transport Molecules move from areas of low Molecules move from areas of low

concentration to areas of high concentration concentration to areas of high concentration with the aid of ATP energy.with the aid of ATP energy.

Requires protein carriers called Pumps.Requires protein carriers called Pumps.

The Importance of Active TransportThe Importance of Active Transport

Bring in essential molecules: ions, Bring in essential molecules: ions, amino acids, glucose, nucleotidesamino acids, glucose, nucleotides

Rid cell of unwanted molecules (Ex. Rid cell of unwanted molecules (Ex. sodium from urine in kidneys)sodium from urine in kidneys)

Maintain internal conditions different Maintain internal conditions different from the environmentfrom the environment

Regulate the volume of cells by Regulate the volume of cells by controlling osmotic potentialcontrolling osmotic potential

Control cellular pHControl cellular pH Re-establish concentration Re-establish concentration

gradients to run facilitated diffusion. gradients to run facilitated diffusion. (Ex. Sodium-Potassium pump and (Ex. Sodium-Potassium pump and Proton pumps)Proton pumps)

The Sodium-Potassium PumpThe Sodium-Potassium Pump 3 Sodium ions move out of 3 Sodium ions move out of

the cell and then 2 the cell and then 2 Potassium ions move into Potassium ions move into the cell.the cell.

Driven by the splitting of Driven by the splitting of ATP to provide energy and ATP to provide energy and conformational change to conformational change to proteins by adding and then proteins by adding and then taking away a phosphate taking away a phosphate group.group.

Used to establish an Used to establish an electrochemical gradient electrochemical gradient across neuron cell across neuron cell membranes.membranes. http://www.biologie.uni-hamburg.de/b-online/library/biology107/bi107vc/fa99/terry/images/ATPpumA.gif

The Role of the NaThe Role of the Na+-+-KK++ Pump Pump The most essential role of this ion pump is The most essential role of this ion pump is to maintain theto maintain the

volume of cellsvolume of cells.. The cytosol contains many negatively charged proteins and The cytosol contains many negatively charged proteins and

small molecular weight solutes. These bind ions.small molecular weight solutes. These bind ions. If the ion pumps were not active in expelling more cations If the ion pumps were not active in expelling more cations

than they took into calls, then water would diffuse into cells, than they took into calls, then water would diffuse into cells, eventually causing them to swell to bursting.eventually causing them to swell to bursting.

The NaThe Na++-K-K++ pump pump also establishes gradients of Naalso establishes gradients of Na++ acrossacross the plasma membranethe plasma membrane since it expels 3 Na since it expels 3 Na++ for every 2 K for every 2 K+ +

taken in.taken in. Since these ion gradient contribute to the resting membrane Since these ion gradient contribute to the resting membrane

potential, the Napotential, the Na++-K-K++ pump is electrogenic. pump is electrogenic.

Active Transport 2Active Transport 2: Exocytosis: Exocytosis Movement of large Movement of large

molecules bound in molecules bound in vesicles vesicles out ofout of the cell the cell with the aid of ATP with the aid of ATP energy. Vesicle fuses energy. Vesicle fuses with the plasma with the plasma membrane to eject membrane to eject macromolecules.macromolecules.

Ex. Proteins, Ex. Proteins, polysaccharides, polysaccharides, polynucleotides, whole polynucleotides, whole cells, hormones, mucus, cells, hormones, mucus, neurotransmitters, wasteneurotransmitters, waste

Active Transport 3Active Transport 3: Endocytosis: Endocytosis

Movement of large molecules Movement of large molecules intointo the cell the cell by engulfing them in vesicles, using ATP by engulfing them in vesicles, using ATP energy.energy.

Three types of Endocytosis:Three types of Endocytosis:– PhagocytosisPhagocytosis– PinocytosisPinocytosis– Receptor-mediated endocytosisReceptor-mediated endocytosis

PhagocytosisPhagocytosis ““Cellular Eating” – engulfing large Cellular Eating” – engulfing large

molecules, whole cells, bacteria molecules, whole cells, bacteria Ex. Macrophages ingesting bacteria or worn Ex. Macrophages ingesting bacteria or worn

out red blood cells.out red blood cells. Ex. Unicellular organisms engulfing food Ex. Unicellular organisms engulfing food

particles.particles.

PinocytosisPinocytosis ““Cellular Drinking” – engulfing liquids and Cellular Drinking” – engulfing liquids and

small molecules dissolved in liquids; small molecules dissolved in liquids; unspecific what enters.unspecific what enters.

Ex. Intestinal cells, Kidney cells, Plant root Ex. Intestinal cells, Kidney cells, Plant root cellscells

Receptor-Mediated EndocytosisReceptor-Mediated Endocytosis Movement of very specific Movement of very specific

molecules into the cell with the molecules into the cell with the use of vesicles coated with the use of vesicles coated with the protein clathrin. protein clathrin.

Coated pits are specific Coated pits are specific locations coated with clathrin locations coated with clathrin and receptors. When specific and receptors. When specific molecules (ligands) bind to the molecules (ligands) bind to the receptors, then this stimulates receptors, then this stimulates the molecules to be engulfed the molecules to be engulfed into a coated vesicle.into a coated vesicle.

Ex. Uptake of cholesterol (LDL) Ex. Uptake of cholesterol (LDL) by animal cellsby animal cells

Types of EndocytosisTypes of Endocytosis

What is phagocytosis?What is phagocytosis?

What is pinocytosis?What is pinocytosis?

What is receptor-What is receptor-mediated endocytosis?mediated endocytosis?

SURFACE TENSIONSURFACE TENSION IS THE IS THE TENDENCY FOR A LIQUID TO TENDENCY FOR A LIQUID TO

CONTRACT AS A CONTRACT AS A CONSEQUENCE OF ITS CONSEQUENCE OF ITS

POSSESION OF FREE POSSESION OF FREE ENERGY, SINCE APPROACH ENERGY, SINCE APPROACH TO EQUILIBRIUM IS ALWAYS TO EQUILIBRIUM IS ALWAYS

ACCOMPANIED BY A ACCOMPANIED BY A DIMINUTION OF FREE DIMINUTION OF FREE

ENERGYENERGY..

We’ve all played with We’ve all played with it- water drops being it- water drops being

added one at a time, until added one at a time, until that one drop breaks the that one drop breaks the

surface and the water surface and the water spills out.spills out.

IT IS HARD TO BELIEVE THAT H-BONDS AND SURFACE TENSION IT IS HARD TO BELIEVE THAT H-BONDS AND SURFACE TENSION ARE ENOUGH TO KEEP THE VOLUME OF WATER THAT IS IN ARE ENOUGH TO KEEP THE VOLUME OF WATER THAT IS IN

THESE BEADS STUCK TO THE PLANTTHESE BEADS STUCK TO THE PLANT

What are biologic activities which can be best What are biologic activities which can be best explained in terms of surface tension?explained in terms of surface tension?

PhenomenaPhenomena:: - the spherical form of a falling dro of water- the spherical form of a falling dro of water - a soap bubble floating in the air- a soap bubble floating in the air - a globule of mercury resting on flat surface- a globule of mercury resting on flat surface Applications in the BodyApplications in the Body:: - phagocytosis or ameboid motion- phagocytosis or ameboid motion - absorption of metabolites/nutrients- absorption of metabolites/nutrients - transport of blood- transport of blood

DIALYSIS is the separation of the more DIALYSIS is the separation of the more diffusible from the less diffusiblediffusible from the less diffusible

Types of Cell JunctionsTypes of Cell Junctions

In Animal Cells:In Animal Cells:

Tight JunctionsTight Junctions

DesmosomesDesmosomes

Gap JunctionsGap Junctions

In Plant Cells:In Plant Cells:

PlasmodesmataPlasmodesmata

Tight JunctionsTight Junctions Transmembrane Proteins of opposite cells Transmembrane Proteins of opposite cells

attach in a tight zipper-like fashionattach in a tight zipper-like fashion No leakageNo leakage Ex. Intestine, Kidneys, Epithelium of skinEx. Intestine, Kidneys, Epithelium of skin

DesmosomesDesmosomes Cytoplasmic plaques of two cells bind with Cytoplasmic plaques of two cells bind with

the aid of intermediate filaments of keratin the aid of intermediate filaments of keratin Allows for stretchingAllows for stretching Ex. Stomach, Bladder, HeartEx. Stomach, Bladder, Heart

Gap JunctionsGap Junctions Channel proteins of opposite cells join together Channel proteins of opposite cells join together

providing channels for ions, sugars, amino providing channels for ions, sugars, amino acids, and other small molecules to pass.acids, and other small molecules to pass.

Allows communication between cells.Allows communication between cells. Ex. Heart muscle, animal embryosEx. Heart muscle, animal embryos

PlasmodesmataPlasmodesmata Channels between the cell walls of plant cells Channels between the cell walls of plant cells

that are lined with the plasma membranes of that are lined with the plasma membranes of adjacent cells and smooth ER runs through.adjacent cells and smooth ER runs through.

Allows for the exchange of cytosol between Allows for the exchange of cytosol between adjacent cells; moving water, small solutes, adjacent cells; moving water, small solutes, sugar, and amino acids.sugar, and amino acids.

Ex. Xylem and Phloem in PlantsEx. Xylem and Phloem in Plants

Types of Cell JunctionsTypes of Cell Junctions What is the difference between a What is the difference between a

plasmodesmata, tight junction, gap junction, plasmodesmata, tight junction, gap junction, and desmosome?and desmosome?

DIFFUSIONDIFFUSION

What are the factors which What are the factors which influence diffusion?influence diffusion?

TemperatureTemperature Molecular weightMolecular weight Shape and size of moleculesShape and size of molecules Solubility of gas in the mediumSolubility of gas in the medium Presence or absence of lectrical charge of Presence or absence of lectrical charge of

diffusing solutediffusing solute Ability of diffusing solute to dissolve in lipidsAbility of diffusing solute to dissolve in lipids

DIFFUSION DIFFUSION

DIFFUSIONDIFFUSION

ACTION POTENTIALACTION POTENTIAL

Events During an Action PotentialEvents During an Action Potential

Depolarization – cell goes from inside negative (-) Depolarization – cell goes from inside negative (-) to inside positive(+). Sodium channels open so to inside positive(+). Sodium channels open so sodium diffusively floods in (-70mV toward 58mV)sodium diffusively floods in (-70mV toward 58mV)

Repolarization – Na channels close and K Repolarization – Na channels close and K channels open (returns to inside negative). K channels open (returns to inside negative). K follows its diffusive gradient and K diffuses out follows its diffusive gradient and K diffuses out of the cellof the cell

Hyperpolarization – “undershoot” of resting Hyperpolarization – “undershoot” of resting potential )-75mVpotential )-75mV

Refractory period – time before another action Refractory period – time before another action potential can “fire” potential can “fire”

Next MeetingNext Meeting

Quiz on Cell PhysiologyQuiz on Cell Physiology Membrane Transport MechanismsMembrane Transport Mechanisms Action PotentialAction Potential Assignment: Read on Blood PhysiologyAssignment: Read on Blood Physiology