Physio Exam 1

Physiology

Study of how living organisms function/how the body works

Levels of organization in the body

Cell -> tissue -> organ -> organ system -> organism

Cells

simplest structural units into which a complex multicellular organism can be divided and still retain the function characteristic of life

Tissues

aggregates of differentiated cells with similar properties

Organ

different tissue types joined in a structural unit to serve a common function

Organ system

organs that are linked together to serve an overall function

4 categories of cells/tissue

1. muscle cell/tissue

2. nerve cell/tissue

3. epithelial cell/tissue

4. connective cell/tissue

Muscle cells function

generate mechanical force

- 3 types (smooth, cardiac, skeletal)

Nerve cell function

specialized to initiate, integrate and conduct electrical signals to other cells

Epithelial cell function

Specialized for the selective secretion and absorption of ions and molecules, and for protection

Connective cell function

connect, anchor, and support structures of the body (blood, cartilage, bone, adipose, tendons, ligaments)

4 epithelial cell shapes

1. cuboidal (cube shaped)

2. columnar (elongated)

3. squamous (flattened, scale like)

4. ciliated

2 types of epithelial tissue layering

1. simple (1 layer)

2. stratified (numerous layers)

Where are epithelial cells located?

- surface of body or individual organs

- inner surfaces of the tubular and hollow structures within the body

What do epithelial cells rest on to anchor them down?

Basement membrane

Epithelial cells are held together by...

tight junctions

Function of tight junctions

- form boundaries between body compartments

- function as selective barriers regulating exchange of molecules

What are cells surrounded by?

Extracellular matrix (ECM)

ECM is a mixture of...

1. structural proteins (collagens)

2. adhesive proteins (fibronectin and laminin)

3. protein-polysaccharide complexes (proteoglycans)

Function of ECM

- scaffold for cellular attachments

- transmission of information to help cells regulate their activity

What makes up the extracellular fluid (ECF)?

- plasma (fluid phase of blood)

- interstitial fluid (ISF), surrounding cells within tissues

More (ECF/ICF) in our bodies?

ICF

What separates ICF from ECF

Cell membranes

What separates ISF and plasma? (in the ECF)

Capillary wall

Of the 60% of body weight that is water, what percent is ICF and ECF? Within ECF, what percent is ISF and plasma?

40% ICF

20% ECF (16% ISF, 4% plasma)

French physiologist that described homeostasis for the first time as "a well-regulated internal environment"

Claude Bernard

American physiologist that coined the term homeostasis as the relative constancy of the internal environment

Walter Cannon

Physiological variables that monitored to check maintenance of homeostasis

- blood pressure

- body temperature

- blood glucose/oxygen levels

- intracellular levels of ions

Dynamic constancy

Levels change over short periods of time, but remain relatively constant over long periods of time

Pathophysiology

physiological control mechanisms can no longer control a vital parameter within normal limits (disease)

Homeostatic negative feedback loop key components

- regulated variable

- set point

- sensory input

- integrative center

- effector

(review slide 26 of lecture 1)

Reflex

specific, involuntary, unpremeditated, unlearned, built in response to a particular stimulus

Circadian rhythm

rhythm that cycles approximately once every 24 hours

Adaptation

inherited biological control mechanism

Acclimation

occurs when control mechanisms change in response to prolonged exposure to a stimulus or stress

Plasma membrane consists of what kind of bilayer?

Amphipathic phospholipid bilayer

- interior is hydrophobic

- exterior is polar

Cholesterol role in plasma membrane

Determines membrane fluidity and stability

Plasma membrane contains 2 different types of proteins

- integral (tightly associated with bilayer)

- peripheral (located at membrane surface)

4 major membrane transport mechanisms

1. simple diffusion

2. facilitated diffusion

3. primary active transport

4. secondary active transport

Simple diffusion

movement of molecules from one location to another as a result of their random thermal motion

- passive (no energy expended)

- high concentration to low concentration

Net flux

sum of 2 opposed unidirectional fluxes

- for passive diffusion it is linearly related to concentration gradient

- indirectly proportional to distance

Fick's Law

Net flux is directly proportional to

1. concentration gradient

2. permeability coefficient

3. area of membrane

Permeability Coefficient

Directly proportional to lipid solubility of solute

- inversely proportional to size of solute

What moves easily across membrane vs does not diffuse readily

- Lipophilic substances move easily across the lipid bilayer of cell membranes

- Polar molecules and hydrophilic molecules do NOT diffuse readily across membranes

3 types of "gated" channels

1. ligand gated

2. mechanically gated

3. voltage gated

Ligand gated channel

Activated by binding of a chemical signaling agent

Mechanically gated channel

Activated by physical deformation of the surrounding plasma membrane

Voltage gated channels

Activated or inactivated by changes in the membrane potential

Membrane potential

Voltage gradient across plasma membrane caused by separation of electrical charges

- provides an electrical force that influences the movement of ions across membrane

Facilitated diffusion

Integral protein binds to specific solutes

- with concentration gradient

- no ATP (energy) coupling

Active transport

Uses energy to move an ion/solute against its concentration gradient

Difference between primary active transport vs secondary active transport

Primary - uses ATP

Secondary - uses electrochemical gradient

Na+/K+ ATPase

- present in all cells

- pumps 3 Na+ out and pumps 2 K+ in using ATP

Steps of Na+/K+ ATPase

1. ATP binds directly to Na+/K+ Pump. 3 Na+ ions bind to intracellular surface of transporter

2. ATPase on, ATP is broken down and transporter is phosporylated

3. Changes shape of transporter and Na+ is released outside the cell

4. K+ ions bind to extracellular surface of transporter, dephosphorylating the transporter

5. Induces a conformational change, changing the shape of the transporter, and K+ is released inside the cell

What is often used to "power" secondary active transport systems?

Na+ gradient

Symport

Refers to the co-transport of coupled solutes in the same direction across the membrane

Antiport

Refers to the transport of a solute out of the cell, in opposite direction than Na+ across the membrane

- Na+ driven

Endocytosis

Allows molecules to ENTER the cell

3 types of endocytosis

1. pinocytosis (vesicles engulf extracellular fluid)

2. phagocytosis (immune cells engulf bacteria or large debris)

3. receptor-mediated endocytosis (specific proteins on the outer surface of the membrane recognize a ligand and activate membrane invagination)

Exocytosis

Allows molecules to EXIT the cell

- system to secrete membrane-impermeable molecules and/or replace portions of the plasma membrane

Apical membrane of epithelial cell

faces a hollow chamber

Basolateral membrane of epithelial cell

faces blood vessels

Transcellular transport (form of epithelial transport)

Movement into a cell, through the cytosol, and exit across the opposite membrane

- different ion channels for apical and basolateral membranes

Paracellular transport (form of epithelial transport)

Diffusion through the paracellular pathway is limited by the presence of tight junctions between adjacent cells. tight junctions form a seal around apical ends of cells

Capillary endothelium

- wall of a capillary composed of a single layer of epithelial cells

- separates plasma from ISF

- has a high permeability to solutes and water

- plasma has higher protein content, but everything else pretty much the same

4 types of chemical messengers that make cell-to-cell communication possible

1. neurotransmitters

2. hormones

3. paracrine agents

4. autocrine agents

Receptor

specialized area of the cell membrane that are sensitive to chemicals and when activated cause the cell to change its behavior

- most are transmembrane proteins

4 key features in ligand-receptor binding

1. Specificity: receptors only bind to specific messengers

2. Affinity: force of binding between messenger and receptor

3. Saturation: degree to which receptors on a cell are occupied

4. Competition: diff molecules w same structure compete for same binding site

Agonist

messenger that binds to receptor and triggers NORMAL response

Antagonist

molecule that binds to receptor and does NOT elicit a response

Down-regulation

cells develop decreased sensitivity

- high extracellular concentration of messenger -> total # of receptors for that messenger decrease

Up-regulation

cells develop increased sensitivity

- low extracellular concentration of messenger -> total # of receptors for that messenger increase

Integrated response

a single messenger molecule can orchestrate an integrated, whole body response

- molecule binds to receptors on multiple cell types

- for example, epinephrine has different effects in different cells

• liver: increased glycogen breakdown

• skin: constriction of blood vessels

• muscle: dilate blood vessels

• heart: increased heart rate

How can a response be terminated?

- decreasing the concentration of the chemical messenger

- sequestration or downregulation of the receptor

Lipid-soluble primary messengers

- move through lipid bilayer of cell membrane

- receptors are mostly intracellular

- trigger gene transcription and protein synthesis

Water-soluble primary messengers

- Lipid-insoluble, hydrophilic

- Cannot pass through lipid bilayers

- Receptors are plasma membrane proteins

- Activated receptors initiate a second messenger cascade that ultimately produces a cell's response

4 types of water-soluble primary messengers

Receptors that:

1. Function as Ion channels

2. Function as Enzymes

3. Interact with cytoplasmic enzymes

4. Interact w G-proteins

Receptors that function as enzymes

- binding of primary messenger causes autophosphorylation of receptor

- activated receptor interacts with intracellular second messenger

Receptors that interact with cytoplasmic enzymes

Activated receptor binds intracellular Janus kinases (JAK)

JAK kinases

Phosphorylate intracellular proteins in the second messenger cascade

G protein structure

Heterotrimeric (alpha, beta, gamma subunits)

- alpha subunit binds and hydrolyzes GTP, and interacts with and activates effector proteins

- beta and gamma subunits anchor protein in membrane

6 step sequence of events for G protein regulation

1. GDP (inactive) binds to alpha subunit, and inactive G protein binds to a receptor

2. primary messenger binds to GPCR, receptor undergoes conformational change -> increased affinity of Ga subunit for GTP (active form)

3. GTP replaces GDP on alpha subunit, and it splits from beta-gamma complex

4. a subunit activates another membrane bound protein and effector cascade begins

5. alpha subunit hydrolyzes GTP to GDP and inorganic phosphate, and returns inactive

6. inactive alpha subunit associates back to beta-gamma complex, G protein binds to receptor, and system restarts

cAMP pathway

1. Ligand binding to a receptor causes G protein activation

2. a subunit of G protein activates adenylyl cyclase

3. Adenylyl cyclase converts ATP to cAMP

4. cAMP activates a cAMP-dependent kinase (usually PKA)

5. Activated PKA phosphorylates intracellular proteins to induce cell’s response

6. Termination of the signaling cascade is caused by phosphodiesterases that convert cAMP to linear AMP OR by protein phosphatases that dephosphorylate proteins

Diff between CNS and PNS

CNS - brain and spinal cord

PNS - nerves

Nervous sytem functions

- sensory function

- motor function

- regulation of function of other systems

- MAINTAIN HOMEOSTASIS

- states of consciousness, attention, learning, memory, etc.

Parasympathetic vs sympathetic

Para - rest and digest

sympathetic - fight or flight

Somatic NS

Neurons innervate skeletal muscle (voluntary)

Autonomic NS

Neurons innervate smooth and cardiac muscle, glands, GI tract (involuntary)

Ganglion

assembly of neuronal cell bodies

Neurons

Nerve cell

- basic functional unit of NS

- transmit info by electrical/chemical signaling

- terminally differentiated, non-dividing cells

Glial Cells

Support neurons through physical and metabolic mechanisms

Cell body (soma)

Contains nucleus

Dendrites

Accept neuronal signaling from other neurons

Axon

Carries electrical signal down neuron towards axon hillock

Axon Hillock

where action potentials are generated

Myelin

Insulation for electrical current traveling down axon

- increases rate of signal conduction

- made by Schwann cells in PNS and oligodendrocytes in CNS

2 types of axonal transport and what they are

Anterograde - Move AWAY from cell body

Retrograde - Move TOWARDS cell body

Tetanus Toxin

Leads to spastic paralysis by reaching and blocking inhibitory neurons in CNS -> irreversible muscle contraction

3 functional classes of neurons

- Afferent neurons

- Efferent neurons

- interneurons

Afferent neurons

SENSORY neurons

- transmit information TO CNS

- cell bodies outside CNS