Animal Physiology Exam 1

Lecture 1/2: Homeostasis

• Homeostasis: taking action to keep body processes functioning to

maintain a “set point.”

• Maintains Homeostasis through: Feedback Loop (Negative and Positive) and Law of Mass Balance

Law of Mass Balance: Law states that if the amount of a substance in the body is to remain constant, any gain must be offset by an equal loss.

Homeostatic Control Systems:

• Local Control: a response restricted to the area

  where the change happened. This is a response

  at the cellular or tissue level

• Reflexive Control: A long-distance response that

  uses Neurological or Endocrine signaling (or both)

Input Signal→ Integrating Center→ Output Signal

Biological Rhythms: Patterns of physiological changes that follow a regular cycle, often influenced by environmental cues such as light or temperature.

Equilibrium ≠ Homeostasis

External environment → Extracellular Fluid (ECF) →|Cell Membrane| Intracellular (ICF)

• Homeostasis and equilibrium are not the same- Equilibrium implies that the two compartments are of identical composition; the ICF and ECF exist in a state of disequilibrium called Dynamic Steady State

Starling Forces

Forces that influence the movement of fluid.

Pi= Oncotic Pressure (pulling)

P= Hydrostatic Pressure (Pushing)

Body Fluid Compartments:

TOTAL BODY MASS (BM)- The 60-40-20 Rule

Total Body Water (TBW)= 60% of total body weight

2/3 is ICF (40% BM)

1/3 is ECF (20% BM) — 75% is interstitial (ISF) (15% of total BM)

                                          25% is plasma (PV) (~5% of total BM)

Calculating TBW, ICF, ECF, ISF, and PV:

Determine the TBW, ICF, ECF, ISF and PV in a 40kg person and an 85kg person.

40kg Person:

• TBW: 40kg x 0.6 = 24L

• ICF: 24L x 2/3= 16L

• ECF: 24L x 1/3= 8L

  • ISF: 8L x 3/4= 6L

  • PV: 8L x 1/4= 2L

85kg Person:

• TBW: 85 × 0.6= 51L

• ICF: 51L x 2/3= 34L

• ECF: 51L x 1/3= 17L

  • ISF: 17L x 3/4= 12.75

  • PV: 17L x 1/4= 4.25

Practice Problem for you to try on your own- Calculate the Body fluid measurments for a 65kg person (Click Triangle at start of heading to reveal answers):

• TBW: 65kg x 0.60= 39L

• ICF: 39L x 2/3= 26L

• ECF: 39L x 1/3= 13L

  • ISF: 13L x 3/4= 9.75L

  • PV: 13L x 1/4= 3.25 L

Lecture 7: Intro to Action Potentials

Resting Membrane Ions:

• Na+ → outside

• K+ → inside

• Ca2+ → outside

• Cl- → outside

• Protein → inside

  • Think of “Salty Banana in Milk” for remembering where the ions are in regard to the cell membrane

Resting Membrane Potential (RMP) Maintained by Potassium Leak Channels

Cell Membrane Receptors

The most rapid signal pathways change ion flow through channels:

1. Ligand Gated

2. Mechanically Gated

3. Voltage Gated

4. Always open

Voltage-Gated Sodium Channel

a) At the resting membrane potential, the Activation Gate is Closed; the Inactivation Gate is open

b) A depolarizing stimulus arrives at the channel, causing the Activation Gate to Open; Inactivation Gate is still open

c) With both the Activation Gate and the Inactivation Gate open, Na+ enters the cell.

d) Inactivation Gate closes and the Na+ entry stops- refractory period.

e) During repolarization caused by K+ leaving the cell, the two gates reset to their original positions.

Efferent v Afferent

• Efferent: Side outgoing→ signal of the presynaptic neuron

• Afferent: Side incoming→ signal of the postsynaptic neuron

Synapse: The region where an axon terminal communicates with its postsynaptic target cell; made up of the presynaptic axon terminal, the synaptic cleft, and the postsynaptic dendrite

Membrane Potentials: Resting, Graded, and Action

When cells are able to change their membrane potential in response to a stimulus they are called excitable

• Gated Potential: subthreshold changes in membrane potential due to chemically gates channels opening and closing

• Action Potential: starts when membrane potential voltage crosses threshold

Threshold: The critical voltage that a cell’s membrane must reach to trigger an “all or none” action potential→ typically -55mv.

• Subthreshold Graded Potential: A graded potential starts above threshold (T) at its initiation point but decreases in strength as it travels through the cell body. At the trigger zone, it is below threshold and therefore does not initiate an action potential.

• Suprathreshold Graded Potential: A stronger stimulus at the same point on the cell body creates a graded potential that is still above threshold by the time it reaches the trigger zone, so an action potential results

• EPSP- Excitatory Post-Synaptic Potential

  IPSP- Inhibitory Post-Synaptic Potential

Temporal Summation: Occurs when two graded potentials from one presynaptic neuron occur close together in time. If close enough together in time, it can summate and reach threshold at the trigger zone and initiate an action potential. ESPS’s added up essentially.

Spatial Summation: Summation of several subthreshold signals results in an action potential.

Anatomy of an Action Potential

The Action Potential begins at the Axon hillock and travels along the axon all the way to the synapse at the post-synaptic neuron

• Action potentials are not generated at the Dendrites or the Cell Body of the Neuron

• Action Potentials start when the voltage crosses the Threshold Potential due to Voltage-gated channels opening and closing

Presynaptic Neuron:

1. Voltage-regulated calcium channels are triggered by an action potential, causing them to open. Ca2+ flows into the axon terminal. (Remember our salty b

2. Ca2+ then triggers changes in the proteins of the presynaptic membrane and synaptic vesicles. Ca2+ causes the synaptic vesicles to fuse with the membrane of the presynapitc axon terminal. The inside of the synaptic vesicle is now in communication with the synaptic cleft.

3. Neurotransmitter is released into the synaptic cleft by diffusion.

Postsynaptic Neuron:

4. The neurotransmitter is now moving across the synaptic cleft to bind to the chemically regulated receptors of the postsynaptic dendrite’s membrane or target cell.

5. Chemically regulated Na+ channels open and sodium enters, following the concentration gradient.

6. Na+ diffuses across the cell body and starts depolarizing- if it reaches the axon hillock with enough Na+ to reach threshold, the action potential is carried down the axon to trigger voltage-regulated Na+ channels at the axon terminal (Shit starts over).

The axon that has carried the initial action potential down the axon then enters a refractory period and will not be activated again until resting-membrane potential is restored.

Continuous Conduction v. Saltatory Conduction

• Continuous occurs in non-myelinated axon

• Saltatory occurs in myelinated axon

Lecture 6: Cell Communication

Local Communication:

• Gap Junctions- Connexins

  • form direct cytoplasmic connections/ bridges between adjacent cells

  • the most direct and rapid form of communication

• Contact Dependent Signals- Surface molecules (Cell Adhesion Molecules/ CAMs) from one cell bind to CAMs from another cell.

• Chemical Diffusion- chemicals sent to cells close by- either Paracrine or Autocrine Signals.

  • Autocrine signals act on the same cell that secreted them

  • Paracrine signals are secreted by one cell and diffuses to adjacent cells

Long-Distance Communication

Can be either electrical, chemical, or both electro-chemical. The Major type of Cell Communication. However, only a cell with the appropriate receptor protein can bind to the chemical signal.

Ligand- The signal molecule that binds to the receptor and initiates a response.

Agonist- a molecule that also activates the receptor and triggers a response

Antagonist- a molecule that binds to and block the activity of a receptor

Cell Membrane Receptors- Gated Ion Receptors

Gated Ion Channels

The most rapid signal pathways change ion flow through channels:

1. Ligand-Gated- These are also known as Chemically gated Channels (Ligand = Chemical). The binding of the ligand to the receptor causes the channel to open, changing the permeability of the cell and the ion composition of the ICF/ECF

2. Voltage Gated- the voltage-gated sodium channel exists in one of three states, only one of which is open:

   1. the closed (resting) state: activation gate closed, inactivation gate open (channel closed)

   2. the open (activated) state: activation gate open, inactivation gate open (channel open)

   3. the inactivated (refractory) state: activation gate closed, inactivation gate closed (channel closed)

3. Mechanically Gated

4. Always open

G-Protein Coupled Receptors

G Proteins linked to amplifier enzymes make up the bulk of all known signal transduction mechanisms

• Includes a 7 Transmembrane Receptor and a trimeric G-Protein with three subunits: Alpha, Beta, + Gamma.

  • Alpha subunit activates adenylyl cyclase.

• The two common amplifier enzymes for GPCR’s are Adenylyl Cyclase and Phospholipase C

• The Main GPCR Pathways are:

  • cAMP Pathway (G alpha s)

  • PLC Pathway (G alpha q)

cAMP = Cyclic Adenosine Monophosphate-

• Major Functions:

  • 1) Second Messenger that amplifies the original signal

  • 2) Activation of Proteins- Most importantly, Protein Kinase A, which Phosphorylates enzymes, ion channels, and transcription factors

  • 3) Regulation of MANY Cell Processes

Activated G Alpha s subunit activates the enzyme Adenylate Cyclase (AC) - AC converts ATP – cAMP (Increasing cAMP), cAMP then acts as a second messenger and Activates Protein Kinase A (PKA)

Phosphodiesterases (PDEs) - primary function is to degrade cAMP and cGMP – which regulates the cellular response→ cAMP Pathway Inactivation

Phospholipase C Pathway

• Alpha Q activates an enzyme in the membrane named Phospholipase C (PLC) which converts membrane phospholipids into:

  • Inositol Triphosphate (IP3) and diacylglycerol (DAG) (2 Lipid-Derived second messengers)→ these are the second messengers.

  • DAG- Directly activates Protein Kinase C

  • IP3- Causes release of Ca from the Smooth Endoplasmic Reticulum

  • Ca2+ acts as a 3rd messenger

Catalytic Receptors

• 2 Subfamilies:

  • Receptor Enzymes

  • Integrin Receptors

Up-Regulation: The target cell inserts more receptors into its CM

Down-Regulation: A decrease in receptor number

Calcium

Ca enters the cell through channels that are either:

1. Voltage-Gated

2. Chemically-Gated

3. Mechanically-Gated

Ca2+ is released from storage sites inside the cell. Most Ca is stored in the Endoplasmic (Sarcoplasmic) Reticulum

Gases as Signaling Molecules

Nitric Oxide (NO), Carbon Monoxide, + Hydrogen Sulfide

In Tissues, NO is synthesized by Nitric Oxide Synthase, then NO diffuses into Tissue cells and binds to intracellular proteins converting GTP to cGMP; NO also acts in the brain as a neurotransmitter (NT) and neuromodulator

So NO can be a Second Messenger, a Paracrine Signal, a Hormone or a NT

She explicitly stated we needed to know this:

NO→ Guanyl Cyclase→ GTP→ cGMP→ Relaxation→ Vasodilation→ Blood Pressure decreases

• Gap Junction: Cells connected by connexins that make pores so the cytoplasm of one connects to the cytoplasm of another (Cytoplasmic bridge)

• Occuluding Junctions (Tight Junction) - made up of claudins or occuldins; involve the cytoskeleton and the actin holding them together, blocks the movement of large molecules between the cells. Mainly ions and water getting through but nothing big. Can tend to be more selective depending on where they are located.

• Anchoring Junction: 3 types:

  • Desmosome- cadherins, involved intermediate filaments actin

  • Adherin Junctions- proteins are also cadherins

  • Hemidesmosomes- basement membrane specifically, proteins are integrins

Lecture 5: Cell Membrane

• Epithelial cells are polarized when they are organized into tissues, with different parts of the cell responsible for performing distinct functions.

• Epithelial cells are divided into distinct apical and basolateral domains that differ in function and protein composition.

Epithelial Transport Mechanisms

1. Paracellular Transport- Movement of substances between adjacent epithelial cells, through the intercellular space.

2. Transcellular Transport- Movement of substances inside the cell, from the Apical membrane to the Basal membrane or vice versa.

Animal Cell Membrane (CM)

Cells are able to maintain Homeostasis in their interior because the CM is selectively permeable to small molecules

The CM is selectively permeable because of its Phospholipid Bilayer and its unique structure and polarity

• Some molecules pass freely (diffuse) through the membrane-

  • Gases: Oxygen, Carbon Dioxide

  • Small Polar Uncharged Molecules: Water and Ethanol

• Charged molecules of any size, and larger, uncharged polar molecules (glucose) are unable to cross the CM by passive diffusion. These require specific transport proteins

The Lipid Bilayer

The 3 Main types of Lipids that make up the Bilayer:

1. Phospholipids (most abundant)

2. Cholesterol

3. Glycolipids

These lipids are “self-sealing” because they are Amphipathic (They have a polar and non-polar end)

Cholesterol

Mammalian CM contain large amounts of Cholesterol

Position themselves with their OH (hydroxyl) group (weakly polar) forming a bond with the polar head groups.

• Because of their Rigid Ring structure, Cholesterols will interact with and partially immobilize those regions of the hydrocarbon chains closest to them- it has distinct effects on Membrane Fluidity

  • Too much Cholesterol stiffens the CM and causes pathology → (hardens arteries- only thing holding us back from absolutely housing a pound of bacon.)

Glycolipids

• Ubiquitous across all living organisms

• A lipid molecule containing carbohydrate moieties

• They are Cell Identity markers and are antigenic

• They form part of the glycocalyx (sugar coat) - which gives cells their identity

Gycocalyx

A Carbohydrate coat that surrounds the Cell Membrane formed by the Oligosaccharides of glycolipids and transmembrane glycoproteins

Also composed of Glycosaminoglycans (GAGs)- and these bind to membrane-spanning proteins to anchor it to the cell membrane

The Function of the Glycocalyx

1) Provides a molecular signature to the cell

2) Helps cells adhere to one another

3) Provides protection from digestion by enzymes

The Glycocalyx can do the following-

1) Provides a molecular signature to the cell

2) Helps cells adhere to one another

3) Provides protection from digestion by enzyme

Membrane Proteins Classified by Structure

• Integral Plasma Membrane Proteins- Found all the way through the Bilayer

• Peripheral Membrane Proteins- found only on the outer surface

“All transmembrane proteins are integrated, but not all integrated proteins are transmembrane.” - Sun Tzu probably

Membrane Proteins by Function

1. Channels/Pores

   1. Passive Channels (alway open)

   2. Gated Channels- open or closed by specific stimuli

2. Transporter/Carrier Proteins

3. Receptors (can also be enzymes)

4. Enzymes- some carbonic Anhydrase

5. Cell Adhesion Molecules- cadherins, connexins, claudins, occludins

6. Cell Identity Markers- the glycoproteins, glycolipids of the glycocalyx

Molecular Movement Across the CM

• Passive Transport- No energy (ATP splitting) required + Goes with the Concentration Gradient

  • Diffusion- solutes

  • Osmosis- water

  • Facilitated Diffusion

  • Bulk Flow- pressure

• Active Transport- Energy (ATP splitting) required + Goes against the Concentration Gradient

  • Primary Active Transport

    • Na/K ATPase Pump→ 3 Na+ go out, 2 K+ come in (creates the negative membrane potential)

  • Secondary Active Transport

    • set up by primary active transport stored energy

    • Mechanism of the Na+ Glucose Secondary Active Transporter (SGLT)

• Bulk/ Vesicular Transport

  • Endocytosis

    • Phagocytosis- actin mediated; engulfing macromolecule

    • Pinocytosis- capture small particles from the ECF through miniature vesicles

    • Receptor-Mediated Endocytosis- Clathrin-coated vesicles

  • Exocytosis

Membrane Potential

• Membrane potential is defined as the voltage difference between the inner and outer surfaces of the cell membrane

• Ions are not distributed evenly between the ECF and ICF.—> This system is in chemical disequilibrium, with concentration gradients for all four ions

• The CM acts as an insulator to prevent free movement of ions between the ICF and ECF

  • K is always leaking out

  • Na is always leaking in (though to a lesser extent)

~K IONS ARE THE KEY PLAYERS IN MEMBRANE POTENTIAL~

Since there is always a little exchange, there is always a need to reestablish- So we have the Na/K ATPase Pump (which maintains the Resting Membrane Potential)

• For each ATP split: 3 Na out and 2 K in

Lecture 4: Metabolism- unfinished (probably not gonna finish)

A network of highly coordinated chemical reactions in which the activities taking place in a cell at any given moment are matched to the needs of the cell.→ All of these reactions are mediated by enzymes

• Enzymes: Proteins that speed up the rate of chemical reactions (act as catalysts)

Cellular Metabolism

Cells regulate their metabolism

Lecture 3: Tissues- In work

Capillary Fluid Exchange

Hydrostatic forces again

The Hydrostatic and Osmotic Pressures that produce fluid movement across the capillary wall

Net movement of water OUT is Filtration

Net movement of water IN is Absorption

Forces that influence the movement of fluid:

• Pi = Oncotic Pressure (pulling)- stays the same

• P = Hydrostatic Pressure (Pushing)- decreases as we move towards venule

  • The force of fluid against a wall- PUSHES fluid out into the Interstitium

  • Is opposed by interstitial fluid hydrostatic pressure

Colloid Osmostic Pressure

Pulling Pressure- The pressure exerted by large plasma proteins in the blood that pulls water into the capillaries→ crucial for maintaining blood volume and pressure.

• Does not vary from arterial to venous side

• Interstitial fluid has very little osmotic pressure

4 Major Types of Tissues

1. Nervous

   1. Found in excitable cells (cells that can change their membrane potential)

2. Epithelial

   1. Groups of cells that cover the exterior surfaces of the body line internal cavities and passages and form certain glands

3. Muscle

   1. 3 different types: Smooth, skeletal, cardiac

   2. Excitable cells

   3. Contract to provide movement

4. Connective

   1. Binds the cells and organs together

   2. Bones, Cartilage, blood -

Specialized Connective Tissues

1. Supporting CT

   1. Cartilage

   2. Bone

2. Fluid CT

   1. Distinct collections of cells in a fluid matrix

   2. Does not connect structures or provide mechanical support (because… y’know… fucking fluid :| )

   3. Blood- classified as CT because of its embryonic origins (Mesenchyme); Plasma considered the ECM

   4. Lymph

3. Adipose (fat)

   1. found in the subcutaneous tissues, breast, bone marrow

Connective Tissue- Extracellular Matrix

• ECM is very important Connective Tissue Structure

• The ECM is the extracellular material that is synthesized and secreted by the cells of a tissue→ matrix components are primarily secreted by Fibroblasts

• Composition of the ECM and the mechanical properties depend on the tissue type

ECM always has two basic components:

• Proteoglycans

• Insoluble Protein Fibers (Collagen, Fibronectin, Laminin→ the textural nightmares when you’re eating chicken :’( )

Epithelial Tissue

Definition: Groups of cells that cover the exterior surfaces of the body, line internal cavities and passages, and form certain glands.

Function: Protect the internal environment of the body and regulate the exchange of materials between the internal and external environments

8 Types of Epithelial Tissues:

• Simple Squamous - Alveoli

• Simple Cuboidal - Kidney

• Simple Columnar - Stomach

• Transitional - Bladder

• Stratified Squamous - Esophagus

• Stratified Cuboidal - Sweat gland

• Stratified Columnar - Salivary Duct

• Pseudostratified Columnar - Trachea

Epithelial Cells’ Main Features

1. Polarity

2. Intercellular Junction

3. Basement Membrane (ECM)

4. Supported by Connective Tissue

Five Functional Groups of Epithelium

Polarity:

Intercellular Junctions:

• Gap Junction: Cells connected by connexins that make pores so the cytoplasm of one connects to the cytoplasm of another (Cytoplasmic bridge)

• Occuluding Junctions (Tight Junction) - made up of claudins or occuldins; involve the cytoskeleton and the actin holding them together, blocks the movement of large molecules between the cells. Mainly ions and water getting through but nothing big. Can tend to be more selective depending on where they are located.

• Anchoring Junction: 3 types:

  • Desmosome- cadherins, involved intermediate filaments actin

  • Adherin Junctions- proteins are also cadherins

  • Hemidesmosomes- basement membrane specifically, proteins are integrins