Physiology definition

The study of the normal functioning of a living organism and its component parts, including all of its chemical and physical processes

A cell

Is capable of carrying out all life processes Separated from its environment by a semi-permeable membrane

Tissue

Groupings of specialized cells that carry out related functions EX) Muscle tissue

Organs

Structural and functional units composed of specific types of tissues

Organ systems - How many are in the human body?

Groups of organs with integrated functions help to maintain homeostasis- 10 organ systems

10 organ systems

Integumentary system Immune system Musculoskeletal system Endocrine system Respiratory system Circulatory system Nervous system Digestive system Urinary system Reproductive system

Homeostasis

Maintaining a similar condition

What causes pathological conditions?

Failure of homeostasis Can be: Internal causes - Genetics, autoimmunity, cancer External causes - trauma, chemicals, pathogens Pathophysiology studies the body in a diseased state

Extracellular fluid (What it does and its response to changes in homeostasis)

Surrounds body's cells Constant in composition Exists in a constant steady state EX) constant exchange of Na and K between ECF and cells. ECF has higher Na and Cl and lower K Slight changes in ECF are compensated by the body Large changes in ECF can lead to cell death or malfunction

3 main components of control systems and what do control systems do

Control systems maintain homeostasis 1) Input signal 2) Controller / integrating centre (initiates response) 3) Output signal (creates response) Control systems can be local or long distance

Local control system

Cells in the vicinity of the change initiate the response

Long distance control (Reflex control)

Cells at a distant site control the response

Sensor

Sensor activates by stimulus and sends signal to integrating centre (usually nervous or endocrine system)

Target

Any body cell that receives output signal and responds

Negative Feedback loop

occurs when a system detects a change in a setpoint (impacting homeostasis) and initiates a response that reverses the change, bringing the system back toward its normal range - The response counteracts the stimulus, shutting off the response loop

Positive Feedback loop

The response reinforces the stimulus, sending the variables farther from the setpoint

Covalent Bonds

shared pairs of electrons - energy is required to break the bond - number of bonds depends on the # of unpaired e- in the atoms valence shell

Polar Covalent Bonds

Polar region developed by unequal sharingof electron pairs

Non-Covalent Bonds

Ionic and hydrogen

Ionic and Hydrogen bonding

Ionic bonds – one atom “steals” the other’s electrons e.g. NaCl Hydrogen bonds - weak attractive force between hydrogen and mainly oxygen, nitrogen or fluorine -No electrons are gained, lost, or shared in a hydrogen bond. Instead, the oppositely charged regions in polar molecules are attracted to each other. Hydrogen bonds may occur between atoms in neighboring molecules or between atoms in different parts of the same molecule EX) surface tension of water

What % of the body is water with ions in it?

60% water with ions in it (mostly Na, K, Cl)

Solute and solvent definitions

Solute - any substance dissolved in a liquid Solvent - liquid into which solute dissolves (usually water in biological systems

Hydrophilic and hydrophobic definitions

Hydrophilic - molecules that are soluble in water (polar, can form H-bonds) Hydrophobic - non-polar substances that can’t form H-bonds and don’t dissolve in water

4 Biomolecules (macromolecules)

Carbohydrates Lipids Proteins Nucleic acids (nucleotide - DNA, RNA, ATP, cAMP)

Name these functional groups: NH2, OH, COOH, PO4, H2PO4

1. Amino 2. Hydroxyl 3. Carboxyl 4&5. Phosphate

Lipids

Consist mostly of carbon and hydrogen • Non-polar; not very soluble in water • Difference between fats and oils • Fats = solid at room temperature (mostly animal) • Oils = liquid at room temperature (mostly plant)

Triglyceride

glycerol and 3 fatty acids - acts as energy storage and is broken down for energy

Carbohydrates - Monosaccharides

Carbohydrates – consist of carbon, hydrogen and oxygen (short form CHO) • Pentoses – 5-carbon sugars • Ribose = sugar phosphate backbone of RNA • Deoxyribose = sugar phosphate backbone of DNA Hexoses – 6-carbon sugars • Glucose • Galactose • Fructose

Disaccharides

Glucose + another monosaccharide

2 storage polysaccharides (animal and plant)

Animal - glycogen (liver and muscles) Plant - starch

Nucleotides

A nucleotide consists of: • One or more PO4 groups • A 5-carbon sugar (ribose or deoxyribose) • A nitrogenous base (purine or pyrimidine) • Adenine • Guanine • Cytosine • Uracil • Thymine

Single Nucleotide Molecules

ATP – Adenosine triphosphate (adenine + ribose = adenosine) • ADP – Adenosine diphosphate • NAD – Nicotinamide adenine dinucleotide • FAD – Flavin adenine dinucleotide • cAMP – Cyclic adenosine monophosphate • Key in cell to cell communication

Nucleic Acids

Used for information storage and transmission • RNA – ribonucleic acid (single chain containing four bases – adenine, guanine, cytosine, uracil) • DNA – deoxyribonucleic acid (two strands twisted together containing four bases – adenine, guanine, cytosine, thymine

Proteins

Contain a carboxyl group (-COOH), an amino group (-NH2) and a hydrogen (H) attached to the same carbon (C) properties hydrogen amino • “R” group is variable, and determines functional properties of the amino acid Proteins are the body's main source of nitrogen Proteins are the most complex and varied shape of the macromolecules * Have specialized functions

Protein structure

• Primary structure - The sequence of amino acids in a peptide chain amino alpha helix acids beta sheet • Secondary structure – alpha helix or beta sheet (formed by covalent bonds between amino acids) folding • Tertiary structure – folding of the chain or sheet to produce a subunit • Quaternary structure – multiple subunits combine

2 main subgroups of proteins

1. Fibrous - Beta sheet or alpha helix - insoluble in water - important structural components of cells and tissues EX) Collagen, keratin, elastin 2. Globula proteins • Fold back on themselves • Have pockets, channels and protruding knobs • Shape stabilized by covalent bond, hydrogen bonds and Van der Waal forces

7 functions of proteins

1) Act as enzymes -speed up reactions 2) Membrane transporters either or passive channels or active pumps 3) Signal molecules - hormones 4) Receptors - bind signal molecules and initiate cellular responses 5) Binding proteins - bind and transport 6) Immune defense - antibodies 7) Regulatory proteins cell turn processes on /off , up down

Enzymes, Transporters, and structural proteins

• Enzymes control synthesis and breakdown of carbohydrates, lipids, structural proteins and signal molecules. Speed up rate of reactions (catalysts) without being consumed. Holds substances in place so they can react with each other, exhibit specificity, competition, and saturation • Transporters and pores (made of proteins) control the movement of molecules in and out of compartments/cells • Proteins make up the structural skeleton of cells and tissues • They are constantly being made and broken down

Specificity

ability of a protein to bind a certain ligand or group of ligands • Ligand and protein binding site must be complementary

Competition

two or more ligands can compete for a binding site

Saturation

all of the proteins can be “full” if the concentration of the substrate is high enough

4 factors affecting protein binding

Activation Modulation Antagonists Physical factors

Activation

• Protein is inactive when synthesized • Undergoes transformation to be active (often the removal or addition of a portion of the protein)

Modulation

• Binding of ligand affected by temperature, pH or an inhibitor (chemical, biological, etc.) • Changes protein’s ability to bind or create response

Antagonists

• Decrease the protein’s activity • Can bind and block binding site (competitive inhibition) • Can bind and cause shape change (allosteric inhibition) • Covalent modulators

Physical Factors affecting protein binding

Physical conditions such as temperature and pH (acidity) can have dramatic effects on protein structure and function. • Small changes in pH or temperature act as modulators to increase or decrease activity • Once these factors exceed some critical value, they disrupt the noncovalent bonds holding the protein in its tertiary conformation. • The protein loses its shape and, along with that, its activity. • When the protein loses its conformation, it is said to be denatured

Pros and cons of cell compartmentalization

• Pro: Separate biochemical processes that could otherwise conflict – (e.g. protein synthesis and degradation) • Con: Transport between compartments essential for the body to function properly

Cranial cavity contents

Contains brain

Thoracic cavity contents

heart and lungs

Abdominopelvic cavity

contains digestive organs, reproductive organs, kidneys and urinary bladder

What 2 main compartments are body fluids found in?

Intracellular fluid Extracellular fluid Separated by cell membranes

Volume of intracellular fluid in the body

25L 40% of body weight

Volume of extracellular fluid in the body

15L 0% of body weight

Cell membrane components

Double layer of phospholipids - Two fatty acid chains attached to a glycerol, and phosphate group -Hydrophobic heads and hydrophilic tails - Proteins, carbs, and cholesterol are embedded in the membrane

Functions of Cell membrane

• Physical isolation - separates ECF from ICF • Regulates exchange with environment - entry of ions/nutrients, release of wastes, etc. • Communication between cell and environment - proteins recognize/respond to signals or environmental changes • Structural support – proteins hold cytoskeleton in place, create junctions with adjacent cells

3 types of membrane proteins

1. Integral 2. Peripheral 3. Transmembrane

Integral proteins

Amphipathic proteins that are embedded in the membrane - Are tightly bound - Includes transmembrane proteins

Peripheral proteins

– Attached to other membrane proteins (non covalent interactions) – Includes enzymes and some structural proteins – Anchors cytoskeleton to membrane

Transmembrane proteins

– Span the membrane, loops of amino acid chain stick out into cytoplasm and ECF – Can bind molecules on both sides of the membrane

Cytoplasm/Cytosol

– Semi-gelatinous – Has dissolved nutrients, ions, proteins and waste – “Inclusions” within the cytosol = lipid droplets, glycogen granules and other insoluble particles

Cytoskeleton

Flexible 3-D scaffolding throughout cytoplasm - Microfilaments, intermediate filaments, microtubules

5 main functions of the cytoskeleton

• 1) Provides cell shape • 2) Internal organization (holds things in place, but allows movement when needed) • 3) Intracellular transport (“railroad track”) • 4) Assembly of cells into tissues (connects to protein fibers of other cells in extra-cellular space) • 5) Movement (cilia, flagella, etc.)

Organelles

Membrane-bound compartments used to isolate substances and segregate function

Nucleus

• Contains DNA and controls cell processes double membranes • Has double membranes with pores • Ions and small molecules pass through easily, movement of proteins and RNA is energy dependent

Mitochondria

• Double membrane enzymes DNA ribosomes • Contains enzymes, DNA, and ribosomes (can make its own proteins and replicate itself) • Intermembrane space used for ATP production

Endoplasmic reticulum (rough and smooth)

• Synthesis, storage and transport of biomolecules • Rough ER– protein synthesis • Smooth ER– makes fatty acids, steroids, & lipids • Golgi Apparatus– receives proteins from rough ER and packages them into vesicles

Lysosomes

• Membrane-bound storage/transport vesicle • Digestive system of cell (bacteria, old organelles)

Tissues and 2 compositions

groups of cells performing similar functions -Cells are connected by cell junctions and other support structures - Simple and Complex

4 tissue types

Epithelial Connective Muscle Nerve

Epithelial tissue

Separates internal environment from external environment, controls exchange - Contain one or more layers of cells connected to one another and held in place by protein filaments - Cell junctions can be leaky (capillaries) or tight (kidneys) - 5 types of epithelial tissue

5 types of epithelial tissue

Exchange Transporting Ciliated Protective Secretory

Exchange epithelia

– Lines blood vessels and lungs – Leaky epithelium allowing molecules to pass through

Transporting epithelia

– Regulates exchange of ions/nutrients between internal and external environment – Found in digestive system and kidney – Tight to very tight cell junctions (movement of substances is generally through the cell)

Ciliated epithelia

– Line respiratory system and female reproductive tract – Cilia beat rhythmically to move fluid and particles

Protective epithelia

– Found in mouth, pharynx, esophagus, urethra etc. – Protects areas of high mechanical/chemical stress – Stratified and often toughened by keratin – Short cell life

Secretory epithelial

– Produce and secrete substances into extracellular space – Can be scattered or grouped – Exocrine – release substances to external environment (e.g. sweat, tears, mucus) – Endocrine – substances released into blood to coordinate activities of tissues, organs or organ systems (e.g. hormones)

Connective tissue

Provides structure and support and can be a physical barrier • May be assisted by specialized immune cells • Has extensive extracellular matrix with cells that secrete substances to modify it • Protein content (collagen, elastin, fibrillin, fibronectin) affects properties such as rigidity and elasticity - 6 types

6 types of connective tissue and what they are and do

• 1) Loose connective tissue– Elastic tissues that anchor and support small glands • 2) Dense connective tissue– Dominated by collagen fibres; provides strength or flexibility– Includes tendons (attach muscle to bone) and ligaments (connects bone to bone) • 3) Adipose tissue– Made up of fat (adipose) cells • 4) Blood– Watery extracellular matrix (plasma), consisting of water, ions, organic molecules, blood cells and cell fragments • 5) Cartilage– Solid and flexible with very little blood supply • 6) Bone– Calcified for strength and rigidity

Muscle tissue and 3 types

Contracts to produce force and movement -Excitable (can propagate electrical signals) - 3 types - Cardiac, smooth, skeletal.

Nerve tissue

Transmits chemical and electrical signals from one part of the body to another - Concentrated in the brain and spinal cord but extends all over the body

Simple and complex tissues

Simple - one layer/cell type Complex - several layers/cell types and extensive extracellular material

3 Cell junction types

Gap Tight junctions Anchoring junctions

Gap junctions

–Protein channel that regulates movement of small molecules and ions - creates bridge between adjacent cells •A gap junction forms from the union of membrane-spanning proteins, called connexins, on two adjacent cells –Allows transfer of amino acids, ATP, etc. –Electrical signals can pass directly cell to cell –Channels can open or close (modulated) –Multiple open channels can allow several cells to act together as one multi-nucleated cell (known as a syncytium)

Tight junctions

Restrict movement of material between cells - Membranes fuse together to create a barrier - Can be leaky EX) digestive tract and blood-brain barrier

Anchoring junctions

Protein attachments that anchor cells to each other or extracellular matrix - Allow sheets of tissue in skin and lining of body cavity to resist damage from stretching and twisting

Necrosis

Death of cells

Apoptosis

Programmed cell death - Cell pulls away from neighbours, shrinks and breaks into membrane-bound pieces

Respiration

Consumes oxygen and produces CO2 and water

Energy definition

The capacity to do work - 3 types of work (mechanical, transport and chemical)

Chemical, transport, and mechanical work

Chemical - making and breaking bonds Transport - move ions, molecules etc Mechanical - movement

Kinetic and potential energy

Kinetic = energy of motion Potential = stored energy -Positions of electrons in bonds allow them to store potential energy

1st and 2nd laws of thermodynamics

1. Energy cannot be created nor destroyed 2. Natural spontaneous processes move from a state of order to disorder

Entropy

Measure of disorder in a system - Creating and maintaining order in an open system requires energy, and disorder occurs when open systems lose energy to their surroundings without regaining it, therefore the entropy of the open system has increase

4 chemical reaction types

Combination - A+B -> C Decomposition - C -> A+B Single displacement - A+BC -> AC + B Double displacement - AC + BD -> AD + BC

Free energy of a molecule

The potential energy stored in the chemical bonds of a molecule - Complex molecules have more chemical bonds and higher free energies

Activation energy - high and low

the initial input of energy required to bring reactants into a position that allows them to react with one another. •A reaction with low activation energy proceeds spontaneously when the reactants are brought together. •Reactions with high activation energies either do not proceed spontaneously or else proceed too slowly to be useful.

Exergonic reactions

•Releases energy – energy can be used by other molecules to do work, or is given off as heat - Spontaneous - Reactants have more energy than products - Products are more stable

Endergonic reactions

•Requires the input of energy –Some energy stays trapped in the chemical bonds –Often synthesis reactions (forms a new molecule or complex) - Nonspontaneous - Products are less stable than reactants

Reaction coupling

Energy released from one reaction is used to drive another reaction

5 steps of protein synthesis

1. Gene activation 2. Transcription 3. mRNA processing 4. Translation 5. Post translational modification

Step 1 protein synthesis

•Step 1: Gene activation (nucleus) –Gene = DNA region containing info to make protein –Most genes turned on/off as needed (“regulated”) –Genes for proteins are almost always turned on

Step 2 of protein synthesis

Transcription Location - nucleus - DNA used as a template to create single strand mRNA using complementary base pairs AUGC

Step 3 of protein synthesis

mRNA processing Location - nucleus - Non-coding segments are removed (introns) - mRNA can be activated or destroyed before a protein is created

Step 4 of protein synthesis

Translation Location - cytoplasm -mRNA leaves the nucleus through pores and finds ribosomes in the cytosol -Ribosomes read the mRNA sequence and create the corresponding amino acid chain

Step 5 of protein synthesis

Post translational modification –Cleavage of the amino acid chain –Addition of molecules/groups –Cross-linkages formed –Bottom line – secondary and tertiary structure created

4 factors that affect reaction rate

Temperature Amount of enzyme (catalyst) Amount of reactant pH

What controls enzyme concentration?

The cell controls enzyme concentration to control reaction rate

Enzyme activation

- Can be activated, inactivated or modulated - Some require cofactors (Ca2+, Mg2+) for activation

Metabolism

All chemical reactions that take place in an organism

Catabolism

•break down of large biomolecules (energy released from high energy bonds)

Anabolism

•Anabolism – creation of large biomolecules (transfer of energy into covalent bonds of macromolecules)

Intermediates

Products of one reaction that become substrates for another reaction

5 ways cells regulate metabolism

1. Controlling enzyme concentration 2. Producing modulators that change reaction rates (hormones) 3. Using two different enzymes to catalyze reversible reactions 4. Compartmentalizing enzymes within cellular organelles 5. Maintaining an optimum ratio of ATP to ADP (if ATP is high, production decreases and vice versa)

Glycogenolysis

•is the process by which glycogen is broken down into glucose-1-phosphate to be used for energy production.

Glycolysis

•is the breakdown of glucose; it may be anaerobic or aerobic.

Glycogenesis

•is the process by which glycogen is synthesized from glucose to be stored in the liver or muscle.

Gluconeogenesis

is the conversion of fat or protein into glucose

Oxidative Respiration

•Uses oxygen to generate energy from metabolic fuels (aerobic) •Oxidative ATP production occurs in the mitochondria •Greater energy (ATP) yield than anaerobic systems

Aerobic ATP production

Requires oxygen Citric acid and ETC need oxygen to produce ATP Oxygen provides the electrons for the ETC. Without oxygen, the cycle doesn't operate - Located in mitochondria

Anaerobic ATP production

Doesn't require oxygen Glycolysis doesn't require oxygen - only 2 ATP produced and pyruvate gets turned into lactate(fermentation) - Located in the cytoplasm

What are the end products of the Citric Acid cycle? (Krebs)

For each acetyl-CoA that goes in the following come out: •1 ATP •3 NADH (~2.5 ATP) •1 FADH 2 (~1.5 ATP) Remember that 2 acetyl-CoAs will go into the cycle for every glucose molecule that is broken down - Fats and proteins can enter the CA cycle and be converted to acetyl coA

Fermentation

Pyruvate builds up in the cytoplasm and undergoes fermentation to produce lactate when there isnt enough oxygen present

Osmotic Equilibrium

Water moves freely into and out of cells through aquaporins in a process called osmosis. The free movement allows for water to be equally distributed in the body's compartments

Electrical disequilibrium

Selective movement of solutes means that the body is usually in a state of chemical and electrical disequilibrium

Concentration and Gradient definitions

Concentration = the abundance of something divided by the total volume of the mixture Gradient = the rate of change of a function, the slope

Diffusion and its 7 main properties

the (1) passive movement of solutes (2) from an area of high concentration to low concentration. Rate depends on size of gradient - Solutes move DOWN their concentration gradient and continue until equilibrium is reached - Is rapid over short distances and slow over long ones - Directly related to temp. - Inversely related to molecular weight and size - Can occur in an open system or across a partition if it is permeable

Osmosis

The movement of solvent through a semi-permeable membrane from an area of low solute concentration to high solute concentration

Similarities and differences of osmosis and diffusion

Diffusion - solute and solvent move - no semi-permeable membrane Osmosis - only solvent moves - movement is through a semi-permeable membrane Similarities: Both equalize the concentration of two solutions

Osmolarity

the # of osmotically active particles per liter of solution

3 types of solutions

Iso-osmotic Hyperosmotic Hypo-osmotic

iso-osmotic, hyperosmotic, and hypo-osmotic solutions

Iso-osmotic = two solutions that have the same number of solute particles per unit volume Hyperosmotic = higher number of solute particles per unit volume than comparison solution Hypo-osmotic solution = lower number of solute particles per unit volume than comparison solution

Tonicity

•Different from osmolarity –Has no units –Comparative term –Usually used to describe a solution in comparison to a cell •Also depends on concentration of non-penetrating (can’t cross membrane) solutes

3 types of tonicity

Hypertonic Hypotonic Isotonic

Hypertonic, hypotonic, and isotonic solutions

•Hypertonic Solution: Cell (inside) has lower concentration of non-penetrating solutes than the solution (outside) - cell loses water and shrinks •Hypotonic solution: Cell (inside) has higher concentration of non-penetration solutes than the solution (outside) - cell gains water and can lyse •Isotonic solution: concentration of non-penetrating solutes are the same in the cell and the solution - No net water gain/loss by cell

Cell membrane selective permeability - what can and can't cross

•Lipid and protein composition of membrane determines what can cross •O 2 , CO 2 and lipids cross easily •Ions, most polar molecules, large molecules (usually proteins) either can’t pass at all, or need help to do so (often require energy) •Movement across membrane depends on particle size and solubility-

Passive and Active transport

•Passive transport – does not require energy (simple and facilitated diffusion) and moves molecules WITH their concentration gradient to create a state of equilibrium •Active transport – requires input of energy from an outside source (often ATP)and moves molecules AGAINST their concentration gradient to create a state of disequilibrium

Rate of diffusion and membrane surface area

Directly proportional to membrane surface area - the larger the membrane's surface area, the more molecules can diffuse per unit time

4 Functions of membrane proteins

1. Structural proteins 2. Enzymes 3. Receptors 4. Transporters

Structural proteins

–Connect membrane to cytoskeleton (maintain shape of the cell) –Create cell junctions that hold tissues together –Attach cells to extracellular matrix

Enzymes

–Catalyze chemical reactions taking place on the cell’s external surface or just inside the cell

Receptors

–Part of body’s chemical signalling system –Binding of ligand to receptor usually triggers an intracellular response - Has specificity

Transporters and 2 types

#NAME?

Channel proteins and 3 types

- 2 types of transporter proteins Channel •Link intracellular and extracellular compartments (water-filled passage) •Carries small ions and water •Membrane spanning protein •Generally restricted to water and ions •Can be specific to a particular ion, or to a particular size/charge •Size of channel and charge of amino acids lining it decide what can pass • Can be opened and closed –Some almost permanently open (e.g. water channels) –Gated channels are usually closed until the right signal comes along (regulates ion movement) •Chemically gated channels: opened by messengers either inside or outside the cell •Voltage gated channels: controlled by the electrical state of the cell •Mechanically gated channels: respond to physical forces (temperature, pressure, etc.)

Carrier proteins and 3 things they experience

•Not a direct connection. Bind specific ligand on one side of membrane and release on the other by changing conformation •Transfer of larger molecules •Transports glucose, amino acids, ions, etc. •Found on cell AND organelle membranes •Large complex proteins with multiple subunits •Carrier protein transport is slower than channel proteins 3 things they experience •Specificity –Transporters move only one molecule or closely related group of molecules •Competition –Closely related substrates can compete for transporter binding sites •Saturation –All of the carriers can be full if the concentration of the substrate is high enough

Cotransport, uniport, symport, and antiport

Cotransport – moving more than one type of molecule at a time Uniport - Move only one kind of molecule Symport - More than one kind of molecule being transported in the same direction Antiport - Molecules are carried in opposite directions

Facilitated diffusion (carrier mediated)

•Used for large and/or polar molecules •Carrier protein helps molecule move down the concentration gradient •If gradient reverses, so does transport (if build up inside of cell, the channel reverses) - Higher rate of transport

Primary active transport

•Breaks down ATP to ADP and P i to release energy that drives the pump

Secondary active transport

•Uses potential energy to move molecules •Sodium concentration gradient can be used to cotransport nutrients, ions, and water (either as symport or antiport) •Example: sodium glucose symporter - Sodium is moving down its concentration gradient but glucose is going against its gradient (action is coupled with the movement of Na)

Endocytosis and 3 types

–Membrane surface indents rather than pushing out to engulf a particle –“Constitutive” (essential and ongoing) process that requires ATP –Can be receptor-mediated •Ligand binds to membrane receptor, complex migrates along membrane to a protein-coated pit •Pit sinks in and pinches off to become a vesicle •Receptor returned to surface, ligand processed - Phagocytosis, pinocytosis, and receptor mediated

Phagocytosis

– Cell engulfs a particle into a large membrane-bound vesicle (phagosome) –Phagosome binds with lysosome containing digestive enzymes to digest/destroy particle – Requires ATP for cytoskeleton movement (cellular eating)

Pinocytosis

A type of endocytosis where ECF is taken into the cell cellular drinking

Receptor-mediated endocytosis

Receptors on membrane bind ligand triggering a pit to to form that then pinches off to become a cytoplasmic vesicle

Exocytosis

–Intracellular vesicles fuse with membrane to get rid of molecules that are too big for carriers – Vesicles fuse and release contents to ECF (vesicle membrane becomes part of cell membrane)

Apical and Basolateral membranes

•Apical membrane – faces lumen (internal space) of organ •Basolateral membrane – faces ECF •Each side has different properties to encourage one-way movement of molecules

Transcellular transport

•tight junctions force movement of particles through the cell (requires crossing two membranes)

Paracellular transport

occurs between adjacent cells if junctions are leaky

Epithelial absorption and secretion

•Absorption: movement of a substance from the lumen/ organ to the ECF •Secretion: movement of a substance from the ECF to the lumen

Electrochemical gradient

•Gradient is a form of stored (potential) energy •Oppositely charged molecules coming back together releases energy (can be used to do work) •Changes in membrane potential (due to concentration gradient or membrane permeability) result in nerve signals that cause muscle twitches, hormone release, etc. •Signals are due mostly to the movement of Na + and K +

3 steps of cell (physiological) communication

–1) Simple diffusion across small distances –2) widespread distribution of molecules through the circulatory system –3) rapid, specific delivery of messages by the nervous system

2 types of signals to target cells

–1) electrical (causes change in cells’ membrane potential) –2) chemical (molecules secreted into the ECF)

4 methods of cell-to-cell communication

1. Gap junctions 2. Contact dependent signals 3. Secretory cells 4 Long distance communication

Contact dependent signals

Method of cell-to-cell contact –surface molecules on one cell membrane bind to surface molecules on another cell’s membrane •Cell adhesion molecules (CAMs) act as receptors in cell-cell signalling •Linked to the cytoskeleton or intracellular enzymes

Secretory signals

Method of cell-cell contact cell releases chemicals that diffuse through ECF and act on those close by (paracrine signalling) or on cell that released them (autocrine)

Long distance (cell) communication

Method of cell-to-cell communication involves nerve and/or blood for transportation - signal is released from a distance location and is carried to target via blood (i.e hormones) or nerves

Hormones

chemical signals that are secreted into the blood and distributed all over the body by the circulation - long distance cell communication

Neurocrine System:

The nervous system uses a combination of chemical signals and electrical signals to communicate over long distances. An electrical signal travels along a nerve cell until it reaches the very end of the cell, where it is translated into a chemical signal secreted by the neuron

Signal transduction and its 3 steps

•The process by which an extracellular signal molecule activates a membrane receptor that in turn alters intracellular molecules to create a response 1. Membrane receptor binds extracellular signal molecule (first messenger Ligand) and is activated 2. Ligand binding turns on associated proteins and starts an intracellular response (ligand can bind inside or on the cell membrane) which is a cascade of second messengers 3. The last second messenger in the cascade acts on intracellular targets to create a response Response to the same signal might not be the same in different tissues

Extracellular signal and intracellular signal

•The extracellular signal molecule is the first messenger - The intracellular molecules form a second messenger system

5 steps of a typical animal cell signal pathway

–1) signal molecule (ligand) binds to a protein receptor –2) activation of receptor by ligand –3) receptor activates one or more intreacellular signal molecules –4) last molecule in the pathway initiates synthesis of target proteins or modifies existing target protein for response –5) Negative feedback (build up of product turns off original signal)

Where are target receptor proteins found? What factors impact where binding occurs?

They can be found in the nucleus, in the cytosol, or on the cell membrane as integral proteins •Where binding occurs depends on whether the signal (ligand) is lipophilic or lipophobic – impacts how a signal is received (lipophilic enter cell, lipophobic can’t pass on their own)

Lipophobic signal and 4 receptor types

–Bind to surface membrane receptors and produce effects through a second messenger system/cascade –Last messenger of cascade acts on intracellular targets to create response –Response can include changes to/creation of an enzyme, muscle contraction, cytoskeletal movement, change in protein synthesis, alteration of membrane transport for all 4 receptors the signal is passed across the membrane to initiate intracellular response –1) receptor channels: chemically gated channels that open when the receptor binds –2) receptor enzymes –3) G-protein coupled receptors –4) Integrin receptors

Receptor Channels

•The activation of receptor-channels initiates the most rapid intracellular responses of all receptors •When an extracellular ligand binds to the receptor-channel protein, a channel gate opens or closes, altering the cell’s permeability to an ion. •Increasing or decreasing ion permeability rapidly changes the cell’s membrane potential, creating an electrical signal that alters voltage-sensitive proteins - Type of lipophobic signal

Receptor Enzymes

• Catalytic receptors that have two regions: –A receptor region on the extracellular side of the cell membrane –An enzyme region on the cytoplasmic side –Ligand binding to the receptor activates the intracellular enzyme –Catalytic receptor enzymes include protein kinases - Type of lipophobic signal

G-Protein Coupled Receptors

•Cross the phospholipid bilayer seven times •The cytoplasmic tail of the receptor protein is linked to a three-part membrane transducer molecule known as a G-protein •Inactive G proteins are bound to guanosine diphosphate (GDP) •Exchanging the GDP for guanosine triphosphate (GTP) activates the G protein •When G proteins are activated, they either (1) open an ion channel in the membrane or (2) alter enzyme activity on the cytoplasmic side of the membrane. - Type of lipophobic signal

Lipophilic signal

–Diffuse through lipid membranes to bind with intracellular receptors –Binds to receptor in the cell or nucleus –Activates a specific gene that contains code for synthesizing a particular enzyme –Transcription to mRNA, which leaves nucleus & enters cytoplasm –Binds with ribosomes to direct synthesis of new proteins - Translation (& ultimately physiological response)

Integrin Receptors

•On the extracellular side of the membrane, integrins bind either to proteins of the extracellular matrix or to ligands such as antibodies and molecules involved in blood clotting •Inside the cell, integrins attach to the cytoskeleton via anchor proteins •Ligand binding to the receptor causes integrins to activate intracellular enzymes or alter the organization of the cytoskeleton

Calcium's role in signalling and function

Key signal molecule •Can enter cell through a wide variety of channels, mostly stored in endoplasmic reticulum •Can also be released from intracellular compartments by second messengers –Alter enzyme/transporter activity, channel gating –Movement of contractile proteins (cytoskeleton) –Trigger exocytosis of secretory vesicles –Initiate development of embryo when egg is fertilized –Muscle contraction

Endogenous ligand, agonist ligand, and antagonist ligands

-Endogenous ligand binds to receptor for desired effect - Agonist ligand has a similar active site to the endogenous ligand; binds to the receptor and produces the same effect - Antagonist ligand is close enough in shape to bind to the receptor but not close enough to produce an effect. It stops other ligands from binding and prevents response

How are cellular responses modulated?

•Receptors constantly being made & degraded •Down-regulation –Decrease in receptor number – decrease response –Removal from membrane (endocytosis) or receptor desensitization •Up-Regulation –Target cell inserts more receptors into the membrane –Allows cells to vary responsiveness to signal molecules – increase response •Ligand can be degraded by enzymes in extra-cellular space •Chemical messengers can be taken up into neighboring cells •Endocytosis of receptor-ligand complex (receptor returned by exocytosis) • Bottom line: process initiated by signal can be stopped when necessary

What determines the response? Receptors or ligands?

Receptors

Reflex Pathway 5 steps

1. Stimulus 2. Sensory Receptor 3. Integrating centre 4. Effector 5. Response

Stimulus

Variable moving out of a desired range - It activates sensor - Is eliminated when target cells are reached by output signal –Starts the reaction –Can be changes in temperature, oxygen, blood pressure, etc. (any regulated variable) Example: Body temperature control on a hot day

Sensory receptors and activated sensor

•located throughout the body sense change in stimulus – Central receptors – located in or closely related to the brain (eyes, ears, nose, tongue, central, chemo-, osmo-, and thermoreceptors) – Peripheral receptors – found elsewhere in the body (joints, skin, blood vessels, etc.), for pH, osmolarity, temperature, pressure, etc. Increase in body temperature sensed by thermoreceptors • Activated sensor sends input signal to integrating centre (usually CNS) Thermoreceptors send message to hypothalamus

Integrating centre

Evaluates signal and can send output signal (chemical, electrical) •compares input signal to desired setpoint Hypothalamus assesses if body temperature is > 37 degrees •If signal is out of range, integrating centre initiates output signal Hypothalamus sends message to skin, muscle and sweat glands

Effector

•Output signal travels to target (effector) •7) Effector carries out response to bring variable back to normal –Responses can be cellular or systemic Arterioles dilate, muscles relax, sweating starts, body temperature decreases

Nervous vs. Endocrine Systems Reflex

•Reflex control can be done by one system or both •Nervous and endocrine systems often overlap (neuroendocrine)

Simple vs. Complex Control Pathways

• Simple control pathways generally have one integrating centre – Direct response to a single stimulus –Can be either neural or hormonal • Complex control –Involves more than one integrating centre –Can involve both neural and hormonal (endocrine) control