BME 3111 PHYSIOLOGY & ENGINEERING (Rat Lab)

WHAT IS PHYSIOLOGY?Physiology is the study of the functions of living organismsExplores the mechanisms involved inBirthGrowthSurvival (healthy and disease conditions)Reproduction Ageing and DeathSocratesc. 469 BC 399 BCHippocratesc. 460 BC c. 370 BC Plato423 BC 347 BCAristotle384 BC 322 BCGalen of Pergamon (Galen)129 c.200 ADIbn al-Nafis1213 - ? Leonardo da Vinci 1452 1519Michelangelo 1475 1564Andreas Vesalius 1514 1564William Harvey 1578 1657A little bit of history of physiologyFundamentals of PhysiologyImportant principles that drive most of the physiological processes

Concentration gradient

Pressure gradient

Electrochemical gradient

Conformational changes

HomeostasisHomeostasis maintenance of nearly constant conditions in the internal environmentNegative feedback loopsPositive feedback loopsIn disease conditions, homeostasis is disturbed or impaired (e.g. viral infection leading to high fever)

Conversely, impairment in homeostasis results in disease (e.g. complications resulting from exposure to extreme heat or cold)

Every cell, tissue, organ and organ system is involved in maintaining homeostasisBody temperatureBlood pressureFluid and electrolyte balanceAcid-base balanceBlood gas concentrationsHormonal balance

Homeostasis

Positive feedback loopsMechanism that brings about an ever greater change in the same direction

It has to have a cut-off point Otherwise leads to a vicious cycle and eventual death

Beneficial positive feedback loops Blood clotting Uterine contractions at child birth Positive feedback is in itself part of a negative feedback loop

From Text book of Medical Physiology 11th Ed, Guyton & Hall, 2006Body Fluid CompartmentsThe maintenance of a relatively constant volume and a stable composition of the body fluids is essential for homeostasis

Fluid intake and output are balanced during steady-state conditions

From Text Book of Human Physiology, Guyton, 2006Intracellular 2/3rdExtracellular 1/3rd Interstitial fluid (80%) (tissue fluid) Blood plasma (20%)Transcellular Synovial Peritoneal Pericardial Intraocular Cerebrospinal

Major derivatives of the embryonic germ layers

TissuesTissue - an aggregation of similarly specialized cells which together perform certain special functions

Four primary tissuesConnective EpithelialNervousMuscle

Connective tissue Develop from the embryonic mesoderm

A material made up of fibers forming a framework and support structure for body tissues and organs and surrounds many organs.

A tissue, usually of mesoblastic origin (mesenchyme), that connects, supports, or surrounds other tissues, organs, etc.

Functions of CTConnection of body tissues (cohesion)Binds organs together, hold organs in place, cushions them, fills space. Provides structural framework for the body

Storehouse of salts, minerals and fats (energy)

Major contributor to the homeostatic mechanisms of the body

Protection of organs, repair from injuries

Connective tissuesCollagen Type I fibers

Collagen Type I and elastin fibers

Collagen Type III fibers - branchedCourtesyColor atlas of cytology, histology and microscopic anatomy (Kuehnel W. 2002)Elastic fibers Reticular fibers

Elastic fibers - Aorta

Reticular FibersThyroid Gland

Reticular fibers - Amnion

Elastic fibers - AuricleCourtesyColor atlas of cytology, histology and microscopic anatomy (Kuehnel W. 2002)Ehlers Danlos Syndrome

Caused by a defect in the structure, production, or processing of collagen or proteins that interact with collagen, such as mutations in the COL5A or COL3A genesEpithelial tissueDefinition:Membranous tissue covering internal organs and other internal surfaces of the bodySits over connective tissues (Epi-thelial or upon tissue)Two types of epithelial tissueLining epitheliumGlandular epithelium Functions Barrier, protection, secretion, selective absorption, trans-cellular transport.They are avascular, but innervatedNutrients diffuse Connective tissue Basement membrane Epithelial cells

Types of Epithelial cells

Single-Layered Squamous Epithelium Posterior Epithelium of the Cornea Single-Layered SquamousEpitheliumPeritoneumSerosaSingle-Layered Cuboidal Epithelium Renal Papilla

Columnar epitheliumIntestinesCourtesyColor atlas of cytology, histology and microscopic anatomy (Kuehnel W. 2002)

MicrovilliUterus

Kinocilia Uterus

Transitional EpitheliumUrotheliumUrinary BladderCourtesyColor atlas of cytology, histology and microscopic anatomy (Kuehnel W. 2002)Epidermolysis Bullosa

Skin that is so fragile that it tears or blisters as a result of a minor bump, stumble, or even friction from clothing. Nervous TissueDefinition:

The material that makes up the brain, spinal cord and network of nerves around the body.

Nervous Tissue is:Specialized for the generation and conduction of electrical impulsesComposed of specialized nerve cells called neuronsFunctions alongside supporting cellsGlial cells (CNS)Schwann cells (PNS)Oligodendrocytes (or oligodendroglia)Astrocytes (or astroglia)Monitors sensory input, and integrates it to control body functions such as motility, homeostasis, mental activity etc.

Rett Syndrome

Rett syndrome (RTT), originally termed cerebroatrophic hyperammonemia, is a rare genetic postnatal neurological disorder of the grey matter of the brain that almost exclusively affects females.Muscle TissueDefinition:The substance of muscle, consisting of muscle fibers, muscle cells, connective tissue, and extracellular material.A tissue composed of fibers capable of contracting to effect bodily movement.An extremely elastic, vascular connective tissue that can shorten or elongate to effect movement

Muscle Tissue - Three types Skeletal Striated MultinucleatedVoluntary movements. Smooth No striations One nucleus per cell Cannot be controlled voluntarily.Cardiac Only found in heartStriated One nucleus per cell. Short, branched, and interconnected to form a continuous fabric. Contains intercalated discs that couple adjacent cells mechanically and electrically. Stimulation of one myocardial cell results in stimulation of all other cells (wholehearted contraction).

Striated MuscleCourtesyColor atlas of cytology, histology and microscopic anatomy (Kuehnel W. 2002)Smooth Muscle Radial artery

Cardiac Muscle - Left VentricleBranching and microvasculature in cardiac muscle

Duchenne Muscular DystrophyDuchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy, which results in muscle degeneration and premature death. The disorder is caused by a mutation in the gene dystrophin, located on the human X chromosome, which codes for the protein dystrophin. Dystrophin is an important component within muscle tissue that provides structural stability to the dystroglycan complex (DGC) of the cell membrane. While both sexes can carry the mutation, females are rarely affected.

Cell Membranes andTransport of molecules across cell membranes

DiffusionDiffusion is the spontaneous passive movement Therefore, it is a net movement of molecules in and out of the cell across the cell membrane along a concentration gradient.

Simple Diffusion - GasesPassive transportMovement of non-polar molecules across the lipid bilayer by simple diffusion

Movement of inorganic molecules and water through channel proteins by simple diffusion

Facilitated diffusion of small organic molecules facilitated by carrier proteins

Diffusion gated ChannelsCharged ions such as Na+ and K+ cannot cross plasma membraneIon channels that span membranes allow passage of moleculesSome ion channels are always openSome ion channels are gated (voltage gated and ligand gated) such that the gates open and close in response to particular stimulus

Facilitated DiffusionNet movement from higher to lower concentrationNo ATP requirementCarrier mediated, e.g., glucose transport into cellsIn the unstimulated state, the carrier protein inside vesiclesFor eg., GLUT4 carrier in skeletal muscle fuse with the plasma membrane during exercise and insulin simulation, inserting the carriers into the membrane allowing passage of glucose

Active TransportMovement of molecules against a concentration gradient.Requires ATPE.g., epithelial lining of small intestines, kidneyTwo types of active transportPrimary active transportSecondary active transport (coupled transport)

Primary active transport Occurs when hydrolysis of ATP is directly responsible for function of carriers., e.g. Ca++ pump, Na+/K+ pumpThese pumps are usually ATPase enzymes

Secondary active transport (coupled transport)The energy required for movement of one molecule is derived from the movement of another molecule.Co-transport (symport) - if the two molecules move in same direction. Eg., co-transport of Na+ and glucose from intestinal lumen across the epithelial cellsCounter transport - if the two molecules move in the opposite direction

Rate of diffusionRate of diffusion is affected by

The magnitude of concentration differences across the membrane

Permeability of membrane to the diffusing substance

Temperature of the solution

Surface area of the membrane

Thickness of the membraneOsmosisOsmosis is the net diffusion of solutions or solvents across a membraneThe membrane must be selectively permeable

Two conditionsSolute concentrations must be different across the membrane

Membrane must be relatively impermeable to the solute

Solutes unable to cross a membrane and promotes osmotic movement of water are said to be osmotically active

Osmosis could be prevented by an equal and opposing force (plant cell walls)

Osmotic pressure is the measure of force required to stop osmosis.

Greater the solute concentration, greater the osmotic pressure

MolalityThe amount of solute (moles), divided by the mass of the solvent (weight) (not the volume), represented as mol/kgThe ratio of solute to water molecules is of critical importance in osmosisTherefore, molality is a more desirable measurement of concentration for body fluids

OsmolalityOsmolality is the total molality of a solution (osmoles of solute per kilogram of solvent)

1 mole glucose + 1 mole fructose in 1 kg of water = 2 osmoles of solutes/kg

For solutes such as NaCl that ionize when dissolved in water, 1 mole of NaCl will ionize to 1 mole Na+ and 1 mole Cl- for a total of 2 osmoles of NaCl/kg waterRegulation of Blood OsmolalityMaintenance of plasma osmolality within 1-3% is vital for homeostasis

Dehydration due to strenuous exercise, increased salt intake etc. can increase osmolality

Drinking excessive water reduces osmolality

TonicityIsotonicHypotonicHypertonic