1. Teleological: The purpose/need (why?)

2.Mechanistic: the how a process works. (this is the way we want to think)

1. connection to other disciplines

2. Metaphysics:

a. materialist: reduction lends to this, the matter

i.e. sneezing happens because of irritants in nasal cavity (mechanistic explanation)

b. Non materialist" some things can't be dissected

i.e. dualism

1. Structure of Human Body (Anatomy)

2. Function of the Human Body (Process)

--> Both go together all the time; one informs the other.

1. Aristotle (300 BC)

-every part has a purpose (teleological thinking)

2. Galen (AD 100)

-first to introduce experimental physiology

-advanced the "four humors"

1. william Harvey (1600s)

-dissection, experiment with process, and reason

-worked out the basic or closed circulatory system

-no "vital force" necessary

2.Theodor Schwann (1838)

-cell theory (materialist)

3. Claude Bernard (1865)

-melieu interieur-cell's environment is extracellular fluid

4. Walter Cannon (1932)

-homeostasis: relatively constant internal environment 

1. Nervous System controls internal environment

2. tonic control (levels can be varied)

i.e. diamter of blood vessels

3. Antagonistic control

i.e. digestion- insuling and then hookalah to return

4. Same chemical; different effects

i.e. epinephrine is a hormone and a neurotransmitter.

Goal: maintain optimum environment

1. O₂/CO₂ metabolism

2. Temperature

3. pH

4. Salt/ water

5. nutrients

6. Wastes (nitrogenous)

1. single cell->direct contact with external environment

2. Multicellular environment->indirect contact except with those on the outside.

-cells environment is interstitiual fluid

-optimize by specialized cells, communication and integration (whats done with the information.

-network of body process

1. detect deviation from normal

2. Integrate that information

3. adjust

4. negative feedback to go back to normal

-->if this fails=disease

i.e. body temp: thermoreceptors message to hypothalmus->increase/decrease temp(shiver/sweat)->shuts off when pt is reached.

Compartmentalized by

1. cell membrane (protects and informs transfer)

2. Nucleus (stores information)

3. Cytoplasm (processes information)

1. Controls information

-store, duplicates and expresses-->DNA

2. Process Information

-Rough ER: protein transport; Golgi: proteins where to go.

3. Supply energy

-mitochondria (ATP)

4. Savenging system

-lysosomes: break old cells down; peroxisomes: deals with oxidizing damage

5. Support/ Movement

-cytoskeleton;microtubles (cell division); intermidiate filaments and actin filaments (movement)

Cell Junctions

Cell-cell junctions

-hold tissue together and regulate communication

1.Desosomes:anchor themselves and resist shearing

-cadherin

2.  Tight Junctions: stick together and occlude material from intercellular space

 3. Gap junctions: communicate 

-connexin

Cell junction

cell-matrix junction

-cytoskeleton interact with extracellular proteins

1. Focal adhesion

-integrins "bridge"

-can be static or dynamic. remodeling, signalling due to interactions with extracellular proteins.

1. epithelial

2. Connective

3. Muscle

4. nervous

--separates external/internal environment

1.Types

Simple (1-layer) and Stratified (more than 1 layer) that are attached to the basal lamina

2 Function

a. exchange-rapid passage (i.e. lungs)

b. Transport-selective (i.e. kidney)

c. protective-prevent passage

d. Ciliated- coordinated movement

e. secretory- exocrine and endrocrine cells

-cells associated with extracellular matrix

1. Cells (fibroblasts)

2. Fibroblast secrete extracellular matrix

-matrix made of ground substance (proteoglycans & water) and fibrous protein (collagen)

Types of Connective Tissue(5)

1. Loose Connective Tissue -have fibroblasts; lots of ground substance and some collagen

-provide bulk support for epithelial cells

2. Dense Connective Tissue -have fibroblasts, little ground substance and some collagen -tendons and ligaments

3. Cartilage-Have chondroblasts; collagen; glycosaminoglycans (Chondroitin)

4. Bone-calcified collagen fibers (Cartilage); osteoblasts

5. Blood-RBC (erythorocytes), WBC(leukocytes) and plasma (fibrinogen, albumin, antibodies

1. Phospholipid bilayer with cholesterol

-cholesterol provides structual stability b/c it regenerates

2. Integral membrane proteins (glycoproteins)

1. Physical Barrier

-selective movement (transport proteins)

-communication (receptor proteins)

2. Structual Support

-cell-cell jxn; cell-matrix jxn and cytoskeleton interacts with membrane proteins.

solutes differentially concentrated

1. Chemical- major solute concentration on one side

 2. Electric-ions are major solutes

i.e. body electrons differ on side than the other

-transport of solutes

1. Diffusion-down concentration gradient; noATP

Membrane Transport

Protein mediated transport (3)

1. Membrane Transporters

a. Channel- Pore (grated)

 i. Open-free flow

ii. Gated-regulated flow, signal to open

1.Chemical-influenced by molecule

2. voltage-gated: influenced by charge

3. mechanically-gated: influenced by force

b. carrier proteins: bond substrate, change conformation

2. Facilitated Diffusion (no Atp required)

a. Glucose transport-passive down concentration gradient

-modification of solute maintains gradient; transporter specificity

3. Active Transport-use ATP hyydrolysis to move against conc. gradient

a. 1^o A.T: direct ATP (i.e. Na/K pump)

b. 2^o A.T: indirect ATP use

-molec 1 created ATP, which is then used for molec 2 to go against concentration gradient (i.e. Na/ Glucose transporter)

-using epitelial cells to move something from one side to the other

1. tight junctions uses polarity for this transport

2. polarity gives apical (facing exterior)-symport glucose/Na vs basolateral (inside cell)-Na/K pump; facilitated diffusion glucose

1. Phagocytosis: cell engulfs something with antibodies-actin polymerization/depolymerization

2. Receptor-mediated endocytosis: receptor in membrane bnds something and the entire receptor is engulfed

1. Osmosis: net movement in response to solute diff(where solutes go, water follows-follows 2nd law of Thermodynamics

-osmotic pressure is force needed to oppose movement-balance movement of H₂0

2. Osmolarity (#particles/L); particle dependent, not molec; composition irrelevant

3. Compare solutions by osmolarity; tonicity-water with cell (isotonic, hyper or hypo)

4. Osmosis depends on non-penetrating solutes only.

1. major players: K high inside; Na, Cl-, Ca high outside cell to maintain equilibrium

2. Electrochemical gradient across membrane due to imbalance of K

-resting: steady state of charge

-potential: stored energy available for work

3. Set-up by Na/K pump

a. K high inside, Na high outside

b. K leaky channels to have K move out along conc gradient

c. few Na leaky channgels, not much in cell

d. proteins neg charge b/c of pH e. rmp: -80mV

-diffusion (chm) force is pulling forward and molec hve charge (electrical force) is pulling back

-equil when diff and charge= IEP

no net ion force b/c force of chm gradient=force of electrostatic gradient

Cell-Cell communication

why? and by who?

-Cells communicate to respond to sensory stimuli

-by hormones, immune cells, neronal activity, muscle contraction, cell growth, metabolism

-->all to promote homeostasis

1. Gap junctions- free flow (myocardial tissue)

2. contact-dependent signaling(immune and physically bind)

3. molecules released

a. autocrine :bind cell that secreted it

b. paracrine: bind local cell

c. hormone/neurohormone-secreted by endocrine for longer distance

1. signal molecule binds receptor

2. binding activates intracellular signalling molecules

3. signal molecules affect proteins

4. reach target proteins to specific response

1. cystolic/ nuclear: lipophilic ligands (to go in by themselves); slow i.e. steroid hormones

2. cell membrane receptor (lipophobic ligands)

a. ion channels-chemically gated

b. receptor-enzyme (usually has a tyrosine kinase activity-protein that can phosphorylate)-cell growth/differentiation.

c.G- protein coupled receptor-signal indirectly via G-protein (activated by GDP->GTP)

-Diversity of Roles: sensory transmission, CNS-neuron signalling, immune signaling. peripheral nervous system signaling

d. integrins-associated with cytoskeleton-cell migration in response to outside signal.

-transmit info and amplify signal

1. Primary messenger bind the receptor and result in

i.kinase activation:sequential phosphorylation of target proteins

ii. secondary msgr activation forms and plays role inside cell

i.e. cAMP pathway-undergoes a series of event & alter ion channels, regulate the series and have diverse fxns & amplify the signal for massive response.

2. Post 1^o msgr-kinase cascade (protein phosphorylation)-via receptor kinase-->MAP kinase pathway for cell proliferation

b. 2^o messenger generation (cAMP, phospholipid)-via GPCR

-Adenyl cyclase activates cAMP->protein kinase A->response -Phospholopase C on PIP₂->IP₃+DAG->Ca⁺⁺ release and protein kinase C->response

i.e. secretion in intestine -vasoactive intestinal peptide-VIP bind GPCR->G-protein->adenylase cyclase->cAMP->cystic fibrosis transmembrane regulator ion channel, which releases Cl- into lumen_.water moves into lumen

1. Antagonist ligand binding-blocks receptors activity

2. Up-or-down regulate receptors-physically or functionally (easier to remove)

3. Modify or remove effectors proteins or molecules (post-receptor)

1. Control systems:input (variable change)->controlling center for what to do->output

2. Mech of effector control-nervous Sys,Endocrine Sys

3. methods: tonic control-over a range or Antagonistic Control(A or B) i.e. blood sugar-insulin or glycogen

4. reflex control: response occurs remotley from coordinated resoinse

1. Response loop is under neural and/or endocrine control

2. Neural pathways:specialized cell go to afferent neurons(electrical/chm signal) to CNS(brain/spinal cord) integrating center; efferent neurons (elec/chm) to effector->high specifity, very fast, short duration

3. Endocrine pathways: endrocrine cell sense stimulus, integgrates response, secretes hormoe to effector->low specificity, slower, longer-duration

1. CNS (brain and spinal cord)-make decision

2. Peripheral Nervous System (bring info to and away CNS)i. afferent neurons:receptor->CNS

ii. efferent neurons:CNS->effector

somatic motor division(voluntary skeltal muscle)

automatic division(involuntary smooth, card muscle,digestion)

i. sympathetic-fight or flight

ii. parasympathetic-day to day "rest and digest"

-->both are antagonistic

1. neuron is functional signaling unit:cell body with extensions (dendrites-recieve info;axon-carries outgoing signal

2. Fxn types

a. sensory (afferents)-exteroceptors(outside info, touch, temp), interoceptors (inside info, pain), proprioceptors (position, balance)

b. interneurons (CNS)

c.efferent neurons-somatic motor (voluntary), visceral (autonomic)

3. Glial cells-supporting cast

CNS: oligodendrocytes(myelination),astrocytes(CNS integrity, support neuron activity, uptake or n.t and K, guide blood brain barrier, memory and regulation. PNS: schwann cells (myelinate), satellite (ganglia-provide protection for group of neurons)

-decision made by #of channels, iosform of channels, & gating speeds

2. events:RMP: -80mV, stimulus received in dendrites/ cell body

ii.graded potential reaches trigger zone-threshold reached

iii.voltage gated Na channels open->influx of Na(membrane depolarizes)->channels close 2ms later at +30mV

iv. voltage gated k channels open->K efflux (out of cell)repolarizises membrane to RMP

3. gating voltage-gated Na channels-@ RMP activation gate closes and inactivation gate opens. @threshold, activation gate opens (Na influx) and inactivation gate closes ms later->Na influx stops.

1. RMP: -70mV b/c K high inside, Na high out and K leaks out.

2. Few ions need to cross membrane (depolarization) for a large charge seperation

3. Graded potential: open chem-gated Na channels; loses strength from origin of signal b/c travels like wave

i. in sensory signals are mechanical (pressure), chemical (smell, taste), electromagnetic (photon of light).

ii. in CNA and efferent signal is chemical

iii. "summed" all take place in) trigger zone, threshold must be reached to fire AP

4. A.P: opens voltage-gated Na channels (if enough depolarization, threshold will be reached)-all or nothing

1. Refractory Period: absolute refrac (all channels close, additional AP not possible) or relative refrac (sone Na channels have reset; needs stronger graded stim for threshold)

2. The higher the graded stimulus the higher the rate of AP firing.->relative refaractory overcomes quicker.

1. Ap travels in one direction and does not lose strength

i. (+) charge moves to adjacent space, causes adjacent Na channels to open (depolarize by local current flow)

ii.no backward flow b/c Na channels "behind" in absolute refractory

2. increase speed by axon diameter (faster ion flow), saltatory conduction-less ion leakage by myelin sheaths depolarizing @ node of ranvier sufficient to depolarize  the next node of ranvier

1. Presynaptic cell signal postsynaptic cell by realease of NT into synaptic cleft.

2. synapse-connection btwn pre-post and space btwen (synaptic cleft) NT hold in vesicles-chemical

a. AP reaches axon terminus (at synapse)-voltage-gated Ca channels open and Ca influx signals for vesicles to fuse with membrane. NT is released into synaptic cleft and binds to recepptors found on post

1. Classesi. Acetylcholine (ACH)- CNS, PNS(autonomic, muscle)

ii. catecholamines- CNS, PNS(smooth muscle, glands)

iii. amino acids (CNS)

2. Receptors that bind NT

i.Colinergic (bind Ach) a.nicotinic (ion channels, skeletal muscle)

b. muscarinic (CNS, parasympathetic, GPCR

ii. Adrenergic (bind norepinephrine &epinephrine)-GPCR(activate cAMP and Ca) a. alpha adren->cause smooth muscle contraction blood vessels in GI tract. b. beta adren->cardiac muscle to increase heart rate.

3. effects of receptor activity

i. fast synaptic potentiol by ion channels, short response- depolarization (EPSP) or hyperpolarization (IPSP)

ii. slow synaptic potential by GPCR, longer lasting

1. breakdown in synaptic cleft-acetylcholinesterase

2. recycle to pre-synaptic neuron (norepinephrine, serotonin)

1. Individual neuron recieve many inputs, but only one output

i. fine tune response by neural netweorks

a. convergence- many pre-synap contact smaller number->economize

b.divergence-pre-synap neuron synapse on many->amplify

2. "decision" to fire AP can be modulated

i. summation: (how neurons talk to one another)

a.temporal: change rate of AP by increased graded protential

b. spatial: simultaneous graded potential from different sources)

ii. inhibition

a. postsynaptic(type of spatial-release inhibi nt)-all target cells affected equally

b. presynaptic-selective targets inhibited. 

Cranium-meninges-tissue

1.meninges i. dura mater-thick layer of connective tissue ii. arachroid-web-like connective tisue, CSF iii.pia mater-thin connective tissue

2. tissue i. gray matter (unmyelinated) ii. white (myelinated)

3. CSF

i. ventricles contain choroid plexus (ependymal cells +blood vessel) that secrete CSF; "pulsates" around to cushion brain. which is then returned to blood stream via arachnoil villus.

1. Spinal nevers enter via roots

 i. afferent neurons (sensory) through dorsal root- collect of cell bodies in ganglia (in PNS near dorsal root)

ii.outgoing infor out ventral root

2. Spinal Cord divided into sections-horns

i.afferent (doral horn); outgoing (ventral horn)

ii. gray matter(nuclei-collection of cell bodies in CNS, which synapse)

iii. white matter (axonal extensions-tracts in CNS)

1. Rudimentary functions-brain stem

a. Reticular Formation:sleep/wake cycle

b. medulla oblongata:breathing rate, bld pressure

c. pons-relay structure info between cerebrum (higher fxn) and cerebellum (fine tune)

Homeostatic control

1. thalamus-integrates information to cerebrum

2. hypothalamus-large ctr for homeostasis

Higher Brain Function

1. Gray matter (unmyelinated)

a. cerebral cortex-outer portion 5%

i.divided in functional sections and hemisphere (l&R)

2. White matter-95% of cerebrum

a. interior; helps cerebral cortex for cross commmunication

1. Primary somato sensory cortex: gathers information and coordinates

i. information from skin, skeletal muscles, and internal organ state (stomach aches)

2. Primary motor cortex- plans and executes movements.

3. associative areas-place of integration; cross-communication

encoding->recording (making permanent)->retrieval (conscious)

1. Long term potentiation: induce permanent communication between neurons.

-blind glutamate (excitatory post synaptic potential, CNS)

1. AMDAreceptor (ion cation channel) for normal graded stimuli

2. NMDA receptor (GPCR-Ca channel)-requires glutamate and sufficient depolariztion to be activated 

-graded stimulus strength determines if there is good communication btwn pre-post synaptic neurons

1. increase synaptic transmission

2. week graded stimuli activate AMPA for norm signal

3. stronger graded stimulus - temporal summation

4. increased depol of post syn unblocks NMDA recport and Ca influx acts as 2 msg.

i.Ca dependant kinase phsphorylates AMPA receptor (bring NA and depolarieze), which becomes more active and more responsive to Glutamate

ii.more AMPA receptors in membrane easier depolarization=>gene transcrip

5. retrograde signaling