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Page 1: BIO 203 - Full Semester Package

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uploaded by user pancholi

Class: BIO 203

Lecture/Exam: Full Semester Package

School: SBU

Semester: N/A

Professor: N/A

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Table of Contents

Midterm 1 Material Pages 1-15

Midterm 2 Material Pages 16-46

Midterm 3 Material Pages 47-70

Final Exam Material Pages 71-75

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Lecture 1 (1/24) (Collins)

Physiology – The study of how cells interact with their “environment”

to obtain the things requires for life (water, salts, heat, etc.)

Exchange systems – Systems that allow for the exchange of material.

o For ex. respiratory system, circulatory system, etc.

4 levels of organization – Cellular, Tissue, Organ, and System.

There are 5 Basic Principles

o All Life is Aquatic.

Water is 75% of body weight, 99% of all molecules.

o All life is compartmentalized

Basic unit is the cell

ICF = Intercellular fluid – aka cytoplasm

ECF = extra cellular fluid. There are 2 types:

Interstitial fluid – ECF between cells

Plasma – Blood

Asymmetries between Compartments help maintain a potential

difference. This I needed for physiological functions.

For ex. More Na+ in ICF, and little in ECF.

o All Life deals with the same fundamental problems.

All Life requires an input of energy

ATP is principal form of energy.

This is done through either aerobic (w/ oxygen) or

anaerobic (without oxygen) cellular respiration.

Metabolism – Sum of all energy-requiring life processes.

Metabolic Rate (MR) - metabolism in a unit of time.

Basal Metabolic Rate – Lowest possible (resting) MR.

o All Life is constrained by the laws of physics and chemistry.

Size principle – relationship between surface Area (SA) &

Volume.

As animal gets bigger, the SA/V ratio gets smaller.

This means that relative SA for exchange goes down.

Large animals exchange substances worse, but retain

better.

Small animals exchange well, but retain worse.

o All life can only tolerate a limited range of living conditions.

Ex. H20 level, salts, nutrients, etc.

Homeostasis: maintenance of a relatively constant internal

environment.

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Requires negative feedback

Feedback-

A feedback mechanism has 3 components

o Sensor – checks the level

o Integrator – compares sensor level to set point

and takes an action

o Effector – device used to fix the level back to

set point.

Negative feedback – if things vary from set point –

you act to fix things back to set point

o Ex. Thermostat.

Positive feedback – Positive things lead to more.

o Leads to rapid changes.

o Ex. when you get money, you want more... you

don’t want to return to the previous condition.

o Ex. Waves of contraction during labor stimulate

even more waves of contraction.

Lecture 2 (1/26) (Collins)

A food-energy budget must be maintained.

o Energy in (food) = energy out (work, synthesis ,heat)

Nitrogenous wastes (ammonia) have to eliminate from the body. There

are 3 ways to do this:

o Ammonotelic – get rid of pure ammonia. Lots of water is

needed, but no energy is required. This is used by fish.

o Ureotelic – Ammonia is converted to urea at the cost of ATP.

This makes it less toxic and less water is needed. Mammals use

this.

o Uricotelic – Ammonia is converted to uric acid – requires

almost no water to get rid of, but lots of ATP. This is used

by birds – i.e. bird shit.

Heat can be obtained via 2 methods

o Environment – animals get heat from the environment

o Endogenous – Heat is produced by the animal for itself.

There are 4 ways to transfer heat:

o Conduction – By touching things.

Temperature gradient (T2-T1) is driving force.

Rest is controlled by a constant-

Surface area & length between objects.

Thermal conductivity (metals have most, air least)

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o Convection – By air. There are 2 ways.

Free convection – air doesn’t move; natural heat rises.

Boundary layers form around you, with layers of heat

gradually going from body heat to ambient.

Forced convection– disrupts the boundary layers. Ex. fan.

o Evaporation – Liquids absorb heat from skin and become vapor,

thereby cooling the animal. Ex. Sweating, panting.

o Radiation – just letting off heat through skin. Absorbing heat

due to environment/sunlight.

Counter current heat exchange - When you 2 fluids

flowing in different directions (ex. Veins and arteries

that touch), very efficient heat exchange will occur.

o This is used by mammals and birds to prevent heat

loss in the extremities.

Lecture 3 (1/31) (Collins)

Body temperature (Tb) must be regulated so that enzymes function and

don’t denature.

2 Main strategies for maintaining body temp:

o Ectotherms – Use external heat to thermoregulate

All non-vertebrates, amphibians, reptiles, fishes.

Body temperature is dependent on Tambient.

No insulation. Low MR. Limited physiological change (ex.

vasoconstriction. Behavioral thermoregulation.

o Endotherms – Generate own heat (endogenous) via MR.

Energetically very costly. Used by mammals and birds.

Lots of insulation (fur, etc.). High MR. Physiological

change. Behavioral thermoregulation in addition to

endogenous.)

MR varies with Tamb in Ectotherms.

o At low Tamb, MR is lower, so animal uses less energy and is slow.

o At High Tamb, MR is higher; animal uses more energy and is fast.

MR varies differently with Tamb in endotherms.

o As Tamb gets lower, MR increases to maintain body temp (Shivers)

o At a certain range, you have the thermoneutral zone (TZ).

At this zone, thermoregulation can happen without MR.

Animal’s MR is at the basal metabolic (Resting) rate.

o After you pass the TZ, you use MR to lower body temp (sweating)

Behavioral Thermoregulation – animals use behavior to thermoregulate.

o E.g. stay in the sun in the day, go underground in the night.

o Heliotherm – use the sun as the heat source

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o Thigmotherm – use substrate (earth, rocks, etc.) to get heat.

Thermal acclimation: slow transition from one environment to another

o Done by selective synthesis of different forms of same enzyme

o Isoenzymes – isoforms of enzymes. Only one can be produced at a

time. They have different optimal temps and MR’s.

Heterotherms- Animals capable of varying degrees of heat production.

o Temporal Heterotherms - Tb (hibernation, day/night fluctuations)

Hibernation – regulate Tb, but at much lower level).

Torpor (birds, small mammals – suspend thermoregulation and

let Tb get very low.

o Regional Heterotherms – different temps at a different parts

Ex. Testes in mammals.

Thermogenesis – Converting chemical energy into heat

o Shivering thermogenesis – muscle contractions make heat

o Non-shivering thermogenesis – metabolizing fat to make heat

Brown adipose tissue (BAT) is a specialized fat for this.

It’s found in neck/shoulders in mammals. It heats up

quickly and is highly vascularized.

Temperature is regulated using 3 components. (negative feedback)

o Sensor – measures level.

In humans, this is in preoptic area/anterior hypothalamus

o Integrator – compares level to set point and controls effector.

Set point – the temperature it’s supposed to be at.

In humans, this is in the same area as the sensor.

o Effector – Regulates everything so it returns to the set point.

In humans, effectors are shivering, BAT, etc.

Pyrogens are fever producing substances

o Exogenous pyrogens are very potent and produced by gram negative

bacteria.

o Endogenous pyrogens are produced by the body itself (like from

White blood cells)

They can also be released due to exogenous pyrogens.

Lecture 4 (2/2) (Collins)

Fluid and ion concentrations must be balanced and kept constant

Body fluids are compartmentalized – ICF, Interstitial fluids, Plasma.

Solvent – the liquid that things dissolve in (ex. H20)

Solute – the things that dissolve in solvent – salts, ions, etc.

Diffusion – the movement of things from high conc. to low conc.

o Osmosis – Diffusion of fluids/water.

o Passive – no energy is needed.

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o Driven by the concentration differential (C2-C1).

The cell membrane is selective permeable and highly regulated.

o Hydrophobic substances can easily diffuse through

o Hydrophilic substances cannot pass through directly.

o Lipophobic- molecules that can’t go through the membrane

o Lipophilic – molecules that can diffuse through the membrane.

Cells regulate lipophoic things through aqueous pores (ion channels)

o Aquaporins – special channels for water

o Can open and close as needed.

o Each channel is selective to its own specific ions.

Water balance must be maintained.

o There is no active transport of water – only osmosis.

The concentrations of solutes cause osmosis

o Water moves from areas of less solute (high conc. of water) to

areas of high solute (low conc. of water)

Osmotic pressure – the pressure produced by osmosis

1 osmolars (Osm) ≈ 1 mole/1 liter.

o Molecules can dissociate though.

For ex. NaCl will become NA+ and CL-..

So 1M of NaCl will become 2 osmolars

o Remember as the # of osmolars goes up, it means that the amount

of solute rises. ▲Solute ▲ Osmolars ▼Concentration of water

o Therefore, water flows from low osmolars to high osmolars!

Terms uses to describe osmolarity describe the amount of solute

o –osmotic : used for compartments and non-bio things

Needs a frame of reference! Be careful!

o –tonic: used for cells. Frame of reference is always the cell!

o Hypo – less concentration. Iso – same conc. Hyper – high

concentration.

Ex. compartment A is hypoosmtic to compartment B.

o This means compartment A has less solute compared to B.

o This means compartment A has a lower osmolars than B.

o This means water will flow from A to B.

Lecture 5 (2/7) (Collins)

Osmoregulator – regulate the osmolarity inside the body

Osmoconformer – live isosmotic to the environment. They conform to

the environmental conditions

Euryhaline – animal that survive over a wide range of conditions

Stenohaline – animal that can only tolerate a limited range.

Ionoconformer – uses the same ion concentrations from the environment

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Ionoregulator – regulates the ion concentrations.

Vertebrates are osmoregulates with a Body fluid osmotic concentration

(BFOC) of ~300 mOsm. They have to maintain water budgets!

o Ions balance and water concentrations are linked! Osmolarity is

a function of ion concentration over volume of water

Factors to consider in terms of H2O/ion balance:

o Availability of H20 and salts. Aquatic vs. terrestrial, etc.

o Respiration (passive water loss) and temp for terrestrials.

o Skin (integument) permeability – it varies between animals

Frogs/amphibians : very permeable

Reptiles/desert creatures/birds/mammals: very impermeable

Sweating by humans is an exception. Still impermeable.

o Food – intake of water and salts.

o Excretion – how much is gotten rid of. Skin, salt glands, etc.

There’s a lot of difference between fresh water and salt water fish

o Fresh water has 1 mOsm while fish try to maintain 300 mOsm

Fish gain water and ions from gills, excrete through kidney

o Salt water has 1000 mOsm while fish try to maintain 300 mOsm

Fish drink lots of water and ions.

They lose lots of water and ions through gills.

o Smoltification – remodeling the pumping process in salmon as

they change from freshwater to seawater.

It’s meditated by hormones, and the number and size of

chloride cells that pump out Cl- out of the gills.

Transport epithelia cells are very important!

o Apical membrane – outward facing membrane (external envir.)

o Basal membrane– facing towards inward towards the tissue

o There are transporters on both membranes for through transport.

Epithelial cells are connected by tight junctions

o This means that they form an impermeable sheet of cells.

o Transcellular transport – transport through the cell.

o Paracellular transport – transport between cells (not through)

They are used to pump ions and other substances through the body.

o For ex. glucose from the intestines to the blood stream.

o They have lots of mitochondria to provide the energy needed

o These help to maintain balance of substances and ions.

Lecture 6 (2/9) (Cabot)

The distribution of electrolytes (ions) in fluid compartments (ECF,

ICF, ISS) is main focus.

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o The compartments are all in osmotic equilibrium. The only

exception is that the plasma has more proteins then the rest.

o However, all compartments are in chemical disequilibrium.

o Also, the compartments are in electrical disequilibrium.

Plasma compartment

o Electrolytes (Na, K, Cl, etc.)

o Non electrolytes (glucose, etc.)

o Colloids- large negatively charged proteins.

Major Cations (positive ions): Na+, K+, Ca2+.

o In Plasma – Na+ high

o In ICF- K+ high. Ca2+ very low.

Major Anions (negative ions): Cl-, bicarbonate Hco3-, Phosphate ions.

o In plasma: Cl- and bicarbonate.

o In ICF: phosphate

Balance of charge – the number of charges has to be identical (11+,

11- ) but the actual number of ions doesn’t have to be equal.

Electrical disequilibrium

o Potential difference of about -70mv on the cell membrane

This is the resting membrane potential

This is the difference in potential between the ICF and ECF

Negative inside cell, positive outside.

Membrane potential has many causes

o Separation of the electrolytes between compartments is one.

Permeability of membrane drives the electrolytic imbalance.

Not really the actual change in conc. Of ions!!!

More channels, more permeability.

o Potential can pull ions in as well. called the electrical force

This will lead to the electro-chemical gradient.

Equilibrium potential is the voltage generated in the membrane for a

single ion that the membrane is permeable to.

Equilibrium potential can be calculated using the Nernst equation.

o Nernst potential = equilibrium potential. (units are millivolts)

o It only applies to one ion at a time!

o 61 is a gas constant and all 𝐸𝑖𝑜𝑛 = (61

𝑧) (𝑙𝑜𝑔10(

[𝑖𝑜𝑛]𝑖𝑛

[𝑖𝑜𝑛]𝑜𝑢𝑡))

o Z = valence electrons.

so for ex. +1 for K+; -1 for Cl-; +2 for Ca2+

Goldman-Hodgkin-Katz equation

o Predicts the resting membrane potential for several permeable

ions

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o 61 is a gas constant and all 𝑉𝑚 = 61 ∗ 𝑙𝑜𝑔 (𝑃𝑘[𝐾

+]𝑜𝑢𝑡+𝑃𝑁𝑎[𝑁𝑎+]𝑜𝑢𝑡

𝑃𝑘[𝐾+]𝑖𝑛+𝑃𝑁𝑎[𝑁𝑎+]𝑖𝑛)

o P is the permeability of the specific ion

Permeability are relative

o K really dominates the equation... Pk is almost 40x Pna

o If you are adding other ions to the equation, remember that for

negative ions the concentrations must be flipped (in/out)

Conceptualizing the Goldman equation:

o THINK PERMEABILITY, NOT ION CONCENTRATION

Assume that all concentrations are the same. Only

permeability changes.

o When things are logged, log (1) = 0. All logs over 1 get more

positive as you increase value. All logs under 1 get smaller

when you decrease value

o What this means is that as the numerator of the fraction

increases, the voltage increases.

o When the denominator decreases, the voltage increases.

o Ex. K is more on the inside than out. So it looks like (5/150)

When you increase the permeability, the denominator will

increase more than the numerator. This means voltage

decrease.

Carrier proteins move ions and substances across the membrane.

o There are 3 types:

Uniport – only transports 1 molecule in one direction

Antiport– pumps 2 things in different directions.

Symport – secondary transport – move 2 molecules in 1 way.

o They are never open to both the ECF and ICF at the same time

o Some use ATP, others are facilitated diffusion.

o Some pumps are electrogenic pumps – they help maintain the

electrochemical gradient in the membrane.

o Ex. Na/K pump – pumps out Na, and pumps in K.

Channel proteins form either open channels or gated channel

o They form a pore – continuity between ECF and ICF.

o Open channels don’t open/close. They stay open. Ex. aquaporins.

o Gated channels are very important. 3 types:

Mechanically gated channels

Voltage gated channels (Gated by Na, K, Ca, etc.)

Chemically gated channels (ligand gated channel)

CFTR (cystic fibrosis transmembrane regulator)

o A chemically/ligand gated channel. It’s a Cl- channel.

o cystic fibrosis is a disease when CFTR isn’t able to be inserted

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Disease caused by mucous becoming thick and sticky

o CFTR is regulated by the level of ATP inside the cell.

o In normal conditions – cl- and na+ flow in, H20 can’t go through

membrane, so the conc. of water outside increases – dilutes

sweat.

o If Cl- can’t go into cell (disease) – the sweat is really salty.

o In resp. tract, Cl- leaves cell and brings water with it...

This makes a saline layer that forms under the mucous.

Without saline layer, Mucous will clog up the bronchi

and kill you.

Lecture 7 (2/14) (Cabot)

Equilibrium potential =/= resting membrane potential

o Single ion (Nernst equation) vs. full potential (Goldman eq.)

There 2 types of electrical responses to change in membrane potential

o Graded potential

o Action potential

These changes only happen in Excitable tissue

o This is tissue capable of responding to/generating electrical

signals.

o These are: neural tissue, muscle tissue, and endocrine tissue.

Endocrine tissue cannot generate an action potential!

Membranes are polarized – different charge inside and outside.

o Depolarizing – takes potential to a less negative value.

Causes by increasing voltage(more +) in Goldman equation

o Hyperpolarizing- takes the potential to a more negative value.

Caused by decreasing voltage (more -) in Goldman equation.

Graded potentials must be generated using a stimulus.

o A stimulus applied to a membrane will affect the change in

permeability of the membrane to an ion, leads to voltage change.

As stimulus strength increases, the graded potential’s

amplitude rises proportionally

The amplitude of multiple graded potentials can stack up.

o Graded potentials reduce in amplitude over distance.

Graded potential example: Beta cell (insulin cell) in pancreas

o Low glucose in blood slow metabolism low ATP K+ channel

regulated by ATP stays open K+ leaks outside Ca2+ channel

stays closed no insulin secreted.

o High glucose in blood Fast metabolism High ATP K+ channel

closes due to high ATP K+ stays inside Cell depolarizes

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Ca2+ channel opens (depolarization is only thing that opens the

channel) insulin is secreted.

o It’s important to note that Ca2+ is always needed for

exocytosis.

Action Potentials

o They are triggered by graded potentials that depolarize the

membrane. (Never hyperpolarization, only depolarization!)

o The level of depolarization must be reach a specific level

o Action potentials are all or nothing events –

Once you reach the threshold, it goes all the way,

regardless of what the amplitude of the stimulus is/was.

o Once the potential reaches its peak, it reverses and goes back

to the resting potential.

Example of an action potential: The neuron.

o The action potential can only be generated in the axon hillock

(Beginning of the axon)

It has the special channels needed. These are voltage gated

Na+ channels and voltage gated K+ channels

The voltage gated Na+ channel as 2 gates: an

activation gate and an inactivation gate.

The voltage gated K+ channel has only 1 gate.

o At rest, the activation gates on the Na+ channels are closed.

Same with the K+ gates.

o As the axon hillock depolarizes, voltage gated channels for Na+

open rapidly.

Once it reaches threshold (point of no return), it gets

positive feedback, which accelerates the depolarization.

Depolarization causes increase in permeability for

sodium, causing even more depolarization.

o The depolarization (Called upstroke) continues until it reaches

the peak of the activation potential. It then reverses! Then 2

things happen:

The inactivation gates on the Na+ channel close.

This is different from the activation gates, because

it doesn’t allow the cell to generate another action

potential

This stops the depolarization.

The gate on the K+ channel opens.

This starts repolarizing the cell (Reversing it)

o Once the potential starts coming back down to -70 (resting), it

actually passes it (Called hyperpolarizing phase).

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Some of the K+ channels still open, causing it to pass -70.

Then they close eventually, bring the membrane potential

comes to rest.

Action potential propagation though the neuron:

o The action potential propagates through the axon from the

hillock (Beginning) until the synapse (the end)

o The entry of Na+ causes the flow of electrical potentials

through the axon, thereby having the flow of electricity

traveling through the axon.

Some axons are myelinated, while some aren’t.

o Myelinated – having a myelin sheath – this is a thick fiber that

covers the axon in many layers. It’s like an insulator.

o In some areas, there’s a gap in the sheath- called a node of

Ranvier.

o In the node of Ranvier are where the voltage gated channels are.

o The myelin helps to speed up the reaction because instead of

having the action potential generated every mm, they are only

generated at the nodes of Ranvier, allowing the signal to leap

down the axon, instead of say, crawling.

This is called saltatory conduction.

o Myelination allows very fast speed of propagation.

During an action potential, there is a time interval, called the

absolute refractory period.

o During this, it’s impossible for the membrane to fire another

action potential.

This is due to closed inactivation gates on the Na+

channel.

o This prevents the signal from going back up the way it came.

o The period occurs on the upstroke and repolarization phases, as

they are above the threshold.

The relative refractory period occurs during the hyperpolarization of

the cell

o This is when some of the inactivation gates have opened, but not

all.

o During this, you need more than the threshold to fire another

potential.

The extra power needed lowers as you get close to normal.

Know the difference between Graded and Action Potentials!

Graded Potential Action Potential

Amplitude varies with size of the

stimulus

All-or-nothing. Once membrane

reaches threshold, the stimulus

doesn’t matter.

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Can be summed. Cannot be summed.

Has no threshold. Has a threshold. (usually -15mv)

Has no refractory period. Has a refractory period.

Amplitude decreases with distance. Amplitude stays constant.

Can be a depolarization or

hyperpolarization.

Is only a depolarization.

Initiated by environmental stimulus,

neurotransmitter, etc.

Initiated by a depolarizing graded

potential.

Mechanism depends on ligand gated

channels or other chemical or

physical changes.

Mechanisms depend on voltage-gated

channels only.

Lecture 8 (2/17) (Cabot)

There are 2 types of physiological communication between cells:

o Electrical – communication is not receptor-mediated

o Chemical – communication requires receptor mediation

Gap junctions are a form of electrical communication.

o 2 connexin proteins on each membrane join together to form a

pore.

o Syncytium – when cells are so tightly connected to each other

that they act like a single massive cell.

Chemical communication is done through the use of many signal

molecules

o A Ligand is a primary (first) chemical messenger.

o The ligand can go to any cells in the body.

However, it can only invoke a response in a cell with the

receptor for that specific ligand.

o Many different types of cells can have different reactions to

the same ligand.

This is due to the receptor and how it recognizes the

ligand.

3 types of chemical communication:

o Contact dependent signaling – one membrane has specific

carbohydrates or proteins that match a receptor on the other

cell’s membrane. Ex. antigens in immune system.

o Local signaling: a cell releases the ligand for use in the local

environment.

Autocrine – the messenger released by the cell also binds

to its own membrane, thereby causing changes on itself.

Paracrine – the ligand affects neighboring cells.

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Synaptic transmission is a specialized form of

paracrine signaling in the nervous system.

o Endocrine system – Endocrine cells release hormones into the

blood stream. This allows for widespread signal transduction.

Receptors on target cells are required for the hormone to

have an effect.

Neuralhormone – neurons can insert special hormones into

the blood stream.

Steps of the simple chemical signaling pathway

o A ligand binds to a valid receptor.

o The receptor, changes the conformation. And opens an ion channel

o The ion channel will lead to a cell response.

Some pathways have many relay molecules in a signal transduction

pathway

o The receptor activates relay molecules.

Typically the first one is a G protein.

Substance A will activate substance B, which will activate

Substance C

Substance C will then send out a secondary messenger, like

Ca2+.

o All of these leads to signal amplification and major changes.

o This pathway is the most common.

There are 4 types of receptors. We only need to know 3 of them:

o Ligand gated channels

o G protein coupled receptor

o Receptor enzyme system.

Ligand gated channel

o Binding of the ligand leads to an ion channel opening. Generates

voltage change cell response.

o Example : ACh (acetylcholine) at neuromuscular junction

ACh is a neurotransmitter that binds to the nicotinic ACh

Called this because nicotine can also bind to this

receptor and produce the same response.

Ach causes the ion channel to open. This channel allows Na+

to come in, and K+ to leave the cell. Cell depolarizes.

A depolarizing graded potential is generated.

Antagonist – venom from the snake called a krait will block

the receptor, and cause paralysis leading to death.

G Protein coupled receptor, opens ion channel (simple)

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o A ligand binds to the receptor it changes the G protein that’s

attached to the receptor G protein separates into 3 parts

the 3 parts go and make things happen.

o Example: ACh binding to a G protein, opening an ion channel.

ACh binds to the muscarinic receptor

Called this because muscarine is a toxin from a

poisonous mushroom that activates the receptor too.

G protein separates into the α subunit and a β/γ subunit.

The β/γ subunit opens a K+ ion channel. Cell hyperpolarizes

Antagonist – drugs that block this receptor lead to pupil

dilation and increased heart rate.

G proteins can generate a secondary messenger instead. (complex)

o Ligand binds to receptor, G protein activates, and separates

either the α subunit or the β/γ subunit activate an amplifier

enzyme this enzyme converts an inactive secondary messenger to

an active one Secondary messenger causes cell response.

o Example: G protein-coupled adenylate cyclase-cAMP system

Ligand binds to receptor and G protein splits

Active α subunit activates the membrane protein adenylate

cyclase.

Adenylate cyclase takes ATP and generates cAMP

cAMP activates PKA, which goes around phosphorylating all

kinds of different proteins.

o Example: G protein coupled phospholipase C system

Ligand binds and G protein splits

Active α subunit activates the protein phospholipase C

Phospholipase C breaks up membrane phospholipids called

PIP2 into IP3.

IP3 binds to a receptor on the Ca2+ ion channel of the

endoplasmic reticulum (stores Ca2+)

Ca2+ leads to smooth muscle contraction.

Different receptors have different responses

o Epinephrine will cause dilation in bronchi

It uses an adenylate cyclase system for this.

The Ca2+ secondary messenger causes contraction.

o Epinephrine will cause dilation in arteries

It uses a adenylate cyclase pathway instead

This leads to relaxation.

Tyrosine-kinase receptors

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o When ligands bind, the two proteins of the receptor come

together and activate They become phosphorylated and can

activate up to 6 relay proteins

o Example: Insulin’s (hormone) mechanism of action

Insulin is released due to high glucose levels in the blood

It binds to the receptor, activating lots of reaction

There are transporters that are waiting in vesicles to be

added to the membrane

The activated receptor helps the vesicles attach to the

receptor, which allows more glucose to come into the cell.

There is only pathway that doesn’t use the cell membrane

o Special ligands can pass through the membrane and bind to

enzymes inside the cytoplasm or in the nucleus.

The ligand must be hydrophobic, lipophilic, and small.

Steroid hormones – bind to cytosolic receptors

Thyroid hormones – bind to nuclear receptors.

The receptor determines the response, not the ligand!

Synaptic transmission: transmission from a neuron to other cells.

o Action potential reaches the terminal of the synapse.

o Voltage gated Ca2+ channels open, and Ca2+ flows in.

o Ca2+ causes the exocytosis of neurotransmitter.

It binds to the vesicles and causes them to fuse with the

membrane and dump the load.

Synaptic transmissions must be stopped once they’re done

o Glial cells can absorb the neurotransmitter.

o You can have the neurotransmitter enter the blood stream

o You can chop up the neurotransmitter with an enzyme

This is the case of ACh.

AChE degrades Ach into 2 parts – acetyl and choline

The choline goes back into the cell to be reused

---------------------------End Midterm 1 Material-------------------------

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------------------------- Begin Midterm 2 Material -----------------------

Lecture 9 (2/21) (Cabot) – Intro to CNS & PNS

The nervous system can be broken up into 2 different systems:

o The central nervous system

Made up of the brain and spinal cord

o The peripheral nervous system

Made up of the nerves branching off of the spinal cord

The peripheral nervous system has 2 divisions –

o Afferent division – sensory function. Information going to brain

Somatic sensory – touch, vibration, joint sensations.

Visceral sensory – organ sensations and stuff.

Special sensory – vision, smell, hearing, taste, balance.

o Efferent division – motor information exiting the CNS.

Somatic motor – all of the skeletal muscles

Things you can control and move.

Autonomic motor – visceral/endocrine organs. Blood vessels.

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Things beyond your control.

Cellular constituents of the CNS:

o Neurons

o Glial cells – they are structural and functional. Help neurons.

Outnumber neurons 10:1

Astrocytes – widespread and big.

Maintain chemical environment

Inactivation of neurotransmitters.

Form Blood-brain barrier.

o Surrounds capillaries and controls flow of things

from the blood to the neurons.

Oligodendrocytes – they make myelinated axons.

Schwann cell - Oligodendrocytes in PNS.

Microglia – Scavenger

They act as phagocytes. Clean up debris.

o Ependymal cell – Epithelial cells that line the 4 major cavities

Choroid plexus cells are special ependymal cells and

secrete CSF – cerebral spinal fluid.

There’s 4 huge holes in the brains called ventricles

o There are 2 lateral ventricles (left & right)

o The 2 ventricles dump into the third ventricle.

o Third ventricle joins the fourth ventricle, which runs down the

spinal cord.

Ventricles contain CSF.

o CSF floats the brain (3 lbs.). It weighs like 0.1 lbs. with CSF.

Also serves as shock absorber.

o There’s around ~150 ml

o Choroid manufactures about 500 ml/day

o It leaves through the arachnoid granulations

One way valves that allows the CSF through.

o CSF goes into the Venus sinuses.

CNS divisions –

o Cerebrum (cerebral cortices)

o Diencephalon

o Midbrain (brainstem)

o Pons (brainstem)

o Medulla oblongata (brainstem)

o Spinal Cord.

Rostrocaudal topography – each nerve from the spinal cord serves a

specific area. Ex. nerves from the legs won’t input to cervical

nerves.

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Spinal cord has 2 types of

matter:

o Grey matter – cell bodies of

neurons. Appears gray

o White matter – axons of

neurons. Appears white

because of myelination.

Unmyelinated axons still

outnumber though.

Dorsal root – Sensory info to the

brain.

o Ganglion – group of neurons/ cell bodies

o Dorsal root ganglion - group of neurons/cell bodies.

Ventral root – Motor nerve fibers. 2 types of fibers:

o Somatic – innervate all of the skeletal muscles

o Autonomic – innervates all of the smooth muscle.

Medulla is the most caudal portion of the brain stem

o It is contiguous with the spinal cord

o It regulates blood pressure, heart rate, respiration. Also

needed for walking and standing.

Pons is above the medulla – has a huge bulge on the ventral surface

o Connects cerebral cortex with the cerebellum. Lots of axons for

relaying information. Bulge is full of the axons

o It coordinates respiration and control of lateral eye movements.

Midbrain is at the top of the brainstem. It does a lot

o It process visual and auditory information and feeds the cortex.

o Also involved in movement in limbs and pupils.

o Substantia Nigra is a part of the midbrain

Looks black when you first see it.

Associated with Parkinson’s disease.

Cerebellum sits behind/on top of brain stem. It’s huge.

o Integrates sensory info needed to stand up straight.

o Plans and adjusts motor movement.

o Involved in motor learning. (learning eye/hand coordination)

o We know so much about the cerebellum… but we still don’t know

exactly what it does.

Diencephalon – 2 major pieces – thalamus and hypothalamus

o Thalamus – sensory relay for all senses. Sleep and wakefulness.

o Hypothalamus – thermoregulation, salt and water balance,

endocrine function, stress response, circadian rhythms, etc.

Only region of the brain that is different in males and

females

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Sexually dimorphic nuclei – nuclei are different based

on sex.

Cerebrum – we have 2 cerebral cortexes.

o Left cortex – manages the right side of body. And vice versa.

o We have 4 lobes in a cerebral cortexes

Frontal Lobe– involved in motor function, speech, emotions.

Parietal Lobe – Sensory integration, perceptual awareness.

Temporal Lobe – Auditory center. Language. Memory.

Occipital lobe – Retinal input.

o Hills are called Gyri; valleys are called Sulci.

Increased surface area leads to increased amount of

neurons.

o Corpus collesum – massive fiber tract that joins the 2

hemispheres together.

Somatic motor system: voluntary skeletal muscle movement only.

o α motor neuron is responsible for this. The cell body sits in

the ventral horn of spinal cord. The axon goes to straight to

the muscle and use ACh to cause contraction on nicotinic

receptors.

o Only generates muscle excitation. It’s either excited or not.

Autonomic nervous system – visceral organs and smooth muscle.

o It’s involuntary! Innervates heart, lungs, blood vessels, etc.

o Maintains the stability of our body’s internal environment.

o 3 divisions

Sympathetic

Parasympathetic

Enteric nervous system – does GI tract motility

Sympathetic system –Catabolic system – uses energy

o Global Responses: Fight or Flight, Exercise, Hemorrhage.

o Orthostasis – prone position to standing position. Specific

response.

Parasympathetic system – Anabolic – restorative in function.

o Rest and digest – sleeping, resting, digestion, urination, etc.

Autonomic motor systems are more complex

o Preganglionic neuron – body is in the CNS. Axon synapses on the

ganglion cell in the PNS.

o Postganglionic neuron – cell body is in ganglion. Axon goes to

required place.

o In the sympathetic system, the preganglionic neurons can synapse

on the Chromaffin cells.

These are cells that are part of the adrenal medulla – they

release epinephrine.

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o For parasympathetic system, the synapses at the ganglion use

nicotinic Ach receptors while the synapses at the effector

organs use muscarinic Ach receptions.

o Sympathetic system use nicotinic Ach receptors at the ganglions

as well. However, they can use alpha and beta receptors at the

effector. They can also use NE, DA, and peptides on to of Ach.

o Autonomic system can send excitory and inhibitory signals.

Lecture 10 (2/28) (Cabot)

Muscle Terminology

General Term Muscle Equivalent

Muscle Cell Muscle Fiber

Cell Membrane Sarcolemma

Cytoplasm Sarcoplasm

Modified Endoplasmic Reticulum Sarcoplasmic Reticulum (SR)

Myofibrils do the

contracting.

Excitation –

Somatic neurons send a

single through the

nerve and synapse on

the neuromuscular

synapse.

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Motor unit – a motor neuron and all of the muscle fibers that it

innervates.

o Each muscle fiber is only innervated by one α motor neuron.

The motor end plate (where the axon meets the muscle fiber) and the

sarcolemma are very different from each other.

What happens at the junction:

o The action potential arrives at the axon terminal, and ACh is

released.

o ACh binds to the nicotinic ion-gated channel. Both Na & K can

flow. The motor end plate depolarizes a lot. It sends a graded

potential outward.

To stop the signal, AChE chops up ACh at the motor plate.

o The sarcolemma membrane picks up the graded potential and turns

it into an action potential that propagates along the sarcolemma

and down the T-tubules.

o As soon as the action potential reaches the T-tubules, it opens

a Ca2+ port in the SR.

o The Ca2+ leads to the contraction of the sarcomeres.

Properties of the neuromuscular junction –

o Specialized synaptic junction between an α motoneuron axon

terminal and a skeletal muscle fiber

o The motor end plate potential generated by the synaptic release

of ACh is always a graded, depolarizing potential.

o The amplitude of the end-plate potential is always above the

threshold for action potential generation, and the subsequent

conduction of the action potential into the t-tubules

o When a motor neuron axon terminal depolarizes, and releases ACh,

the underlying muscle fiber contracts.

Skeletal and cardiac muscles are called striated muscle due to the

sarcomeres.

Myofibril structure

o Thin filament

Actin

Tropomyosin (regulatory proteins)

Troponin (regulator proteins)

Tropomyosin runs through the actin. Troponin ____

o Thick Filament

Myosin – has 2 globular heads. Each head has 2 binding

sides.

1 binding site is for the actin

The other binding site is for ATP

o There are 2 proteins that help give structure

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Titin holds the myosin thick filaments.

the longest protein in the body

Nebulin holds the actin thin

filaments.

Sarcomere goes from Z disc to Z disc.

A band is where all of the myosin is.

The H zone is where you have no overlap of

actin and myosin filaments.

M line (center) is where all of the tails of

the myosin are.

I band is where there’s no myosin, only actin

o Center of I band is the Z line/disc.

When a sarcomere moves – the actin filaments slide over the myosin

filaments

o I band and H zone get smaller.

How sarcomeres contract

o At rest, Tropomyosin is like a string that rests on top of the

active sites of the actin.

o Troponin is a calcium binding molecule. It is attached along the

Tropomyosin.

o Calcium binds to troponin, while causes the Tropomyosin to

uncover the active sites of the actin.

o The energized myosin head binds to the exposed active sides and

forms a crossbridge.

o When ADP and Phosphate released from the myosin head, the power

stroke happens – the myosin head pivots, moving the actin

filament back (causing contraction)

o ATP binds, and is used to release the myosin from the actin.

o Myosin head returns to original position with high energy and an

ADP and Phosphate molecule.

o Calcium unbinds from the troponin and calcium pumps use energy

to bring the calcium back into the SR.

Rigor mortis – a few hours after death, the body stiffens up, because

the myosin molecule cannot dissociate from actin due to lack of ATP.

Roles of Ca2+

o It causes release of ACh at the junction

o The resulting action potential down the T-tubule triggers the

DHP receptor (DHPR). DHPR opens a significant ion channel.

There’s a mechanical foot protein that connects the DHPR to the

ryanodine receptor (RyR). The RyR is a Ca2+ channel in the SR

cistern. When DHPR is triggered, the RyR opens, and Ca2+ comes

out. RyR is really what causes the main Ca2+ release, not DHPR.

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Lecture 11 (3/01) (Cabot) – switch gears to cardiovascular system

Cardiovascular system is comprised of blood, heart, and circulation.

Blood

o Plasma is the liquid. Makes up 55% of the blood.

Carries ions, proteins, hormones, etc.

o Cellular elements make up the rest of the 45% of the blood.

Red blood cells (RBCs) (erythrocytes). Majority of the

cells.

White blood Cells – Immune System.

Platelets – Do all of the clotting.

o Hematocrit – the percentage of the blood volume that is occupied

by Red Blood Cells. RBCs occupy about 42-45% of blood.

Heart is one of the most important parts of the blood.

o The apex of the heart is a little left of the centerline. It’s

also close to the chest wall.

o The heart has 4

chambers

2 atria

(Receive

blood)

2 ventricles

(pump blood)

Right side of

the heart

receives

blood from

the blood and

pumps to the

lungs.

Left side of

the heart

receives

blood from

the lungs and

pumps to the

body.

All blood flow is unidirectional! This is due to the 4 valves

o Tricuspid valve – between right atrium and right ventricle

o Pulmonary (semilunar) valve – between right ventricle and

artery.

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o Mitral/bicuspid valve – between left atrium and ventricle.

o Aortic semilunar valve – between left ventricle and aorta.

o Valves open and close passively due to the pressure.

o To open the semilunar valves, the heart must generate more

pressure inside than outside in the blood vessel (Diastolic)

The Left ventricle has more mass/muscle due to the fact that the

system has high pressure circulation (120/80 mmhg) while the right

ventricle pumps low pressure circulation (25/10 mmhg)

o The same amount of blood is pumped by both sides. This is called

stroke volume.

Cardiac output (liters/minute) – amount of blood pumped in liters per

minute.

Mechanics:

o Ventricular systole – period of the ventricular contraction

o Ventricular diastole – period when the ventricle relaxes.

Steps:

1. Ventricular filling – ventricles fill up from the atria

a. At the end of diastole, the atria contract to push blood

into the ventricle.

2. Ventricular systole

a. Isovolumetric contraction – Contraction starts, the AV

valves close, so the ventricle is briefly closed to

everything.

b. Ventricular ejection: the pressure forces the semilunar

valve open and blood is ejected with the heart.

i. Not all blood is ejected however.

3. Isovolumetric relaxation – Ventricular diastole starts.

a. Ventricles relax and the blood backflows, causing the

semilunar valves to close. Ventricles are fully closed.

EDV – end diastolic volume – the most blood in the heart. (~135 ml)

o This occurs right after the atria contract and push blood in.

ESV – end systolic volume – left over blood in ventricles. (~65 ml)

o Occurs right after ejection. Isovolumetric relaxation.

Heart Beat Electrical coordination.

o 1% of cells form the cardiac conducting system

o It all begins at

the SA node.

It sets the

beat of the

heart.

Fires off an

Action

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potential to the AV Node and atria.

o AV node receives the signal and fires off action potentials to

fibers in the bundle of his.

Fibers conduct down all of the way to the apex, and to the

purkinje cells (go up the side of the heart).

o This ensures that atria contract before the ventricle, and that

both don’t contract at the same time.

Atria and ventricles don’t connect or talk to each other;

the bundle of his is the only connection.

The AV node helps delay the ventricular contraction so it

happens after the atrial contractions.

Also ensures that the heart contracts from the apex, and

not the base.

Cardiac muscles aren’t innervated with nerves. Only electrical

signals control them.

o Membrane potentials flow thorough the gap junctions of cardiac

cells called intercalated discs.

o The cells are so interconnected that the cells act as a single

fiber.

o They also don’t have neuromuscular junctions.

SA Node cells are autorhythmic – They generate own cells.

o They are 3 types of voltage ages ion channels: Na, K, and Ca2+.

o Na+ channel is very different – it’s called an HCN Channel.

It has no inactivation and activation gates.

It opens to both Na+ and K+. it’s non-specific

F-type (Funny) voltage-gated channel.

The repolarizing of the membrane causes the opening of the

channel.

3 phases of the action potentials:

o Pacemaker Potential: due to the opening of funny channel.

o Depolarization

o Repolarization.

Action potential at SA Node:

o When Na+ gate opens, the depolarization of the membrane opens

the voltage gated Ca2+ gate at a threshold. This causes the rise

of AP.

o This process takes a long time – 250-300 ms (2-3 ms normal)

o Regular K+ channel ends the AP.

Action potential at muscle: google

o The opening of the gated channels led to a movement of ions

through the gap junctions into the next cell.

o Muscle cells have almost no permeability to the Na+ ions.

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o During repolarizing of the membrane, voltage gated Ca2+ ions

come in.

Slows down the repolarizing and leads to the really long

action potential.

Cardiac muscle respond to action potentials a little differently:

o In skeletal muscles, the opening of the DHPR calcium channel was

insignificant.

The foot protein would open the RyR channel in SR.

o In cardiac muscles, there are no foot proteins; everything is

dependent on the DHPR calcium.

Cardiac cells get Ca2+ from the ECF due to the DHPR.

o The calcium released from the DHPR channel opens the Ca2+ RyR

channel in the SR. (Calcium induced calcium release)

o Cardiac cells must use a passive protein pump to pump out the

Ca2+ back out to the ECF using the inward flow of Na+ to power

the pump.

Cardiac action potential has a huge refractory period… for almost 250

ms. This prevents the contractions from summating and reaching a

tetanus state (max tension.. fully contracted, and not relaxing)

o Autorhythmic cells have no refractory period.

Lecture 12 (3/06) (Cabot)

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ECG – Electrocardiogram – electrical measure of correlated cardiac

mechanical events.

The most important measure is the

electrical axis – from upper right

arm to left leg.

Components of the ECG:

o P wave – Atrial depolarization

Complete discharge of the

SA node.

Contraction of the Atria

happens at the end of the

P wave.

o QRS complex – ventricular

depolarization

Q – contraction of

interventricular septum

(separates left and right

ventricles)

R – contraction of the ventricles from the apex starts.

S – completion of the contraction.

Contraction of the ventricles starts at the top of the R

phase.

o T Wave.

Repolarization of the ventricular muscle.

Ventricular fibrillation – ventricles are contracting all out of

whack.

o Damage to ventricular muscle resulting in uncoordinated

contraction. This can be lethal.

A defibrillator works by depolarizing the heart, which stops all of

the activity. As the heart repolarizes, the SA node will start

sending action potentials again. This resets the system.

Blood pressure

o Systolic pressure – maximum pressure exerted by the blood

against the artery walls.

Results from ventricular systole

Normally around 120 mmhg.

o Diastolic pressure – lowest pressure in the artery

Results from ventricular diastole

Happens right before ventricular systole.

Usually around 80 mmhg.

o Pulse pressure – difference between systolic and diastolic

pressure.

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Blood pressure measurements

o Pump up the blood pressure cuff and collapse the artery

There will be no sound b/c there’s no flow.

o Once you start to lower the pressure, you’ll hear sounds

The pressure when you hear the sounds is the systolic.

The noise is due to turbulent flow through the constricted

the artery. (Period of turbulent flow)

o Once the sounds stop, you reach the diastolic pressure.

Once the pressure releases, the artery goes back to normal

and the turbulent flow stops. (Period of laminar flow)

MAP is the pressure in the aorta.

It’s assumed that when vena cava enters the atrium, their

pressure is 0.

o Mean arterial pressure (MAP)= Diastolic pressure + 1/3 pulse

pressure

Rough estimate.

o MAP = Cardiac output (CO) X Resistance to blood flow (R)

MAP is a dependent variable; CO & R are independent

variables.

CO (L/min) = Heart rate (beats/min) X stroke volume (L/beat)

Heart rate is regulated using SA node pacemaker cells (~ 100 bpm)

o Unregulated (denervated) heart rate = 100 beats/min

o But a normal resting heart rate is 72-80 bpm.

ACh activation of muscarinic receptors in SA nodal cells decrease

heart rate (parasympathetic nervous system cardiac innervation)

o Parasympathetic simulation hyperpolarizes the cells. This causes

the action potential to be generated slower.

NE,E activation of the β-adrenergic receptions in the nodal cells

causes increases in heart rate.(sympathetic system innervation)

o This depolarizes the cells, and increases the slope of the

action potential, causing the potentials to be faster.

Increasing the heart rate – 3 ways to do it

o Increase the β-adrenergic stimulation from the sympathetic

system.

o Withdraw the Muscarinic stimulation from the parasympathetic

system.

o Hormonal control of heart rate – add more plasma epinephrine.

Decrease the heart rate

o Increase the muscarinic stimulation from the parasympathetic

system. (most effective way to do it)

o Withdraw the β-adrenergic stimulation from the sympathetic

system.

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o Decrease levels of plasma epinephrine.

Stroke volume – the amount of blood pumped by each ventricle each

heartbeat. The average is around 70 ml per beat.

o It represents the difference between the EDV(max amount of blood

in the ventricle) and the ESV (blood left over in the ventricle)

o As you increase the EDV, the stroke volume will increase.

Very unique property of

the heart – there is a

range where the heart

muscle can match the

increased volume put

into the ventricle with

output.

Frank-starling curve.

This is important for

when venous return

increases

The venous system can hold blood – it holds up to 61% of blood.

o Squeezing the veins will pump a lot more venous blood into the

heart.

The heart will have to compensate for this by increasing

the stroke volume.

Venous return must equal cardiac output.

Cardiac muscle can also change stroke volume and tension development

by altering contractility.

o Contractility – an increase in

developed tension without a

change in the resting length.

o For any given EDV, if you

increase contractility, you

increase the stroke volume.

o This allows increased CO while

increasing rate.

o Sympathetic system also innervates ventricular muscles cells.

It causes an increase in contractility.

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Recap:

Special properties of cardiac

muscle (Recap):

Can’t be tetanized.

Over a large range of

initial muscle lengths,

increasing muscle length

increases force development

(frank-sterling law of the

heart)

Can increase contracility –

increase tension developed

without changing muscle

length.

Lecture 13 (3/08) (Cabot)

The arterioles in the cardiovascular system are under physiological

control. They are influenced by many things. It’s also called

resistance vessels, because they can restrict blood flow.

o It’s composed of Smooth muscle with layer of epithelium and it’s

under control of sympathetic system. It also responds to

hormones.

o It also responds to paracrine messengers

Blood pressure decreases as it flows through the system, starting

very high at the aorta, and near 0 at the venae cave.

o This is because there is a decrease in flow resistance (R in MAP

= CO X R). (CO constant) High resistance High MAP.

Resistance to blood flow in the system is influenced by:

o Blood flow is opposed by friction.

o Length of vascular system

o Blood vessel radius

o Viscosity of blood (hematocrit)

o Increasing/decreasing resistance manually.

R= (8Lƞ)/( πr4)

o 8 and pi are constants so they aren’t important

o L = Length of vascular system. This is constant unless you are

obese (fat tissue is highly vascularized)

o Ƞ = viscosity of blood. Constant unless at high altitudes.

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o R = radii of arterioles. This is important since it is raised to

the 4th power. Very small changes have very large impacts.

Very small decreases lead to very large increase in MAP.

During normal activity, the sympathetic system makes sure the

arterioles are always contracted at rest. (called vasomotor tone)

NE attaches to α receptors that cause vasoconstriction

Withdrawing the NE will cause vasodilation.

Hormones such as epinephrine, angiotensin and vasopressin cause

vasoconstriction. Epinephrine can cause dilation on β-receptors too.

Local tissue can cause vasodilation due to paracrine resources such

as oxygen

Nitric oxide (EDRF+) also causes vasodilation (Viagra)

Histamine will also cause vasodilation.

Changes in MAP due to peripheral resistance (CO Constant!)

o Will increase if blood vessel length increases (morbid obesity)

o Will increase is hematocrit increases (high altitude)

o Will increase if there is systemic vasoconstriction (decrease in

arteriolar radius)

o Will decrease if there is systematic vasodilation happens.

Capillaries are the exchange vessels. They do metabolic exchange.

o They deliver all kinds of products – O2, CO2, glucose, etc.

o They do primary and secondary active transport.

o Transcytosis – movement of very large molecules (endo &

exocytosis)

Bulk flow is important.

o Mass movement of water and dissolved solutes between blood and

interstitial fluid.

o Function isn’t exchange of nutrients, electrolytes, etc… but

rather the distribution of extracellular fluid (ECF)

o Capillary wall is highly permeable to water and all solutes, but

not large proteins.

Proteins give the compartments different osmotic pressures.

This helps maintain water distribution.

ECF distribution is a balance between capillary blood

pressure and the protein-induced osmotic pressure.

o Filtration – direction of movement is out of the capillary into

the interstitial space into the capillary

o Absorption - direction of movement is into of the capillary into

the interstitial space into the capillary

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o At the arterial end of the capillary, the blood pressure is

greater than osmotic pressure, and fluid flows out of the

capillary. (Filtration)

o At the venule end of the capillary, the blood pressure is lower

than the osmotic pressure, and fluid flows into the capillary.

o More filtration happens than absorption though. (~20L/day

filtrated, 17L/day absorption)

Because you have more filtration than absorption, the lymph system

absorbs the remaining 2-3 L/day and returns it back to the blood.

If you have more absorption than filtration, it leads to interesting

consequences.

o If you bleed, the body can do this to get more fluid into the

blood.

Baroreceptors are nerve fibers that lie in the blood vessel and sense

the blood pressure in both the aorta and the carotid artery.

o Increasing the MAP increases the frequency of firing action

potential of these nerves. And Vice versa.

o The Medulla will interpret the information and generate an

appropriate action. It fixes what needs to be done.

It can change the SA node frequency using the

parasympathetic system. (Heart Rate)

It can use the sympathetic system, it can make the

ventricles contract with more force. (Stroke Volume)

It can also use sympathetic system for changing radius of

arterioles and veins. (resistance of the arterioles)

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Orthostasis – Going from a laying down position to a standing up

position. “I stood up too fast; I feel lightheaded”

o Blood rushes out of the brain suddenly

o Decrease in venous return leads to EDV and stroke volume

decrease. This leads to a decrease in CO and MAP.

o Baroreceptors drop in activity and the brain responds by

increasing sympathetic cardiac and peripheral nerve activity.

You also drop the parasympathetic cardiac nerve activity

(most effective way)

o All of this results in increase heart rate, stroke volume and

resistance. This in effect increases MAP.

Hypertension – chronically increases MAP, BP greater than 140/90.

o Associated with chronically increased total peripheral

resistance, due to decreased arteriolar radius.

o Baroreceptors reset to a new set blood pressure.

o Renal dysfunction can be the cause of hypertension.

o It’s important to treat because the heart is the most affected

organ

Heart has to work harder.

Heart becomes pumped up with muscle and it’s irreversible.

This is called hypertrophy.

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The ventricles get smaller and smaller, and the person will

die due to heart failure.

o Hypertension also increases the chances of stroke and

cardiovascular disease.

Exercising

o EDV, SV, Heart Rate, all go up, leading to a CO increase of 220%

o But the resistance drops, so that the MAP only rises 121%

This is so that more blood gets to the muscle

o Skeletal muscle gets almost 3 times the amount of blood

o The system gets the more blood needed from the veins.

Lecture 14 (3/13) (Cabot) – Kidney function

Kidneys are connected to the ureters which empty into the bladder

Micturition – The act of urinating.

o It is under voluntary and involuntary control.

o The outlet of the bladder is wrapped in skeletal muscles.

(volitional control)

o Smooth muscle is controlled by parasympathetic and sympathetic

nerves. It is involuntary.

During filling.

o The detrusor muscle(main muscle of bladder) is relaxed – allows

the bladder to get bigger and bigger. Sympathetic innervation.

o Skeletal muscle keeps the bladder closed.

o After a threshold however, the brain causes a reflex and causes

micturition.

During micturition

o The skeletal muscle becomes inhibited.

o The detrusor muscle becomes stimulated and contracts.

Function of the mammalian Kidney

o Elimination of metabolic waste products

Urea – protein catabolism

Uric acid - Nucleic acid catabolism

Creatinine - Muscle creatine catabolism

o Regulation of Water and inorganic electrolyte (Na+,etc.) & pH.

o Removal of foreign chemicals (drugs such as penicillin, food

coloring, pesticides, etc.)

o Gluconeogenesis – Generating glucose (extreme fasting only)

o Section of hormones and an enzyme

Erythropoietin (Stimulates RBC production)

1,25-dihydroxyvitamin D3 (important for Ca2+ homeostasis)

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Renin(enzyme)–controls formation of

angiotensin II, which influences

blood pressure and Na+ synthesis)

A nephron is the function unit of the kidney.

They are 2 locations

Cortical nephron

Juxtamedullary nephron.

Not going to be discussed.

Nephron blood flow

o Glomerular capillaries are arranged in a

ball called a glomerulus. This is inside

a capsule called bowman’s capsule (also

called corpuscle)

The space between capillaries in

the capsule is called the bowman

space.

o There is an incoming afferent arteriole, and then the efferent

arteriole leaves

There is no gas exchange here.

o The efferent arteriole

then branches out into

lots of capillary beds

that surround the

tubules all the way

down. (called

peritubular capillaries

in the cortex(top) part)

This is because 99%

of the stuff that

are filtered in the

corpuscle is reclaimed into the blood stream.

So you need lots of vascularization!

Nephron Tubules.

o From Bowman’s capsule (space), everything flows into the

proximal convoluted tubule (PCT), which goes into the descending

Loop of Henle.

o The loop then ascends, and goes into the distal convoluted

tubule (DCT), which then empties into the collecting duct.

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Juxtaglomerular apparatus (JGA)– The

distal tubule becomes in close proximity

to the afferent/efferent arteries.

Composed of:

o Granular cells – synthesis and store

the enzyme renin.

Innervated by sympathetic

nervous system.

o Macula Densa – Cells in the tubules

that are close to the granular cells.

Renal processes

o Filtration - happens in the bowman’s

capsule)

o Reabsorption – happens in capillaries

o Secretion – some solutes are removed

from the blood of the peritubular

arteries and secreted by the tubular

cells into the filtrate (tubes)

o Filtration – amount reabsorbed +

amount secreted = amount excreted.

o Most substances are either reabsorbed or secreted, but not both.

Transport

o Proximal convoluted tubule (PCT)

H+ is secreted.

Bicarbonate, NaCl, Water, Glucose get reabsorbed

o Loop of Henle

H20 & NaCl is reabsorbed.

o Distal tubule - under physiological regulation

o Cortical/Medullar Duct-

K+ is secreted. H20 is reabsorbed.

Fluid in the system

o In Bowman’s capsule and end proximal tubule about 70% of the

filtrate is reabsorbed. Osmolarity remains at plasma level (300)

o At the end of the loop of Henle, 90% is reabsorbed, osmolarity

is 100 mOsm.

o At the end of the collecting duct, osmolarity varies.

Physiological regulation

o Forces generating glomerular filtration

o Regulating of the filtration rate.

o Regulation of reabsorption

o Regulation of secretion.

There are many forces that affect filtration

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o Glomerular hydrostatic pressure – blood pressure – ~60mmhg.

More than regular capillaries (~35 mmhg)

o Capsular hydrostatic pressure oppose filtration - ~15 mmhg

The capsule is full of water, so it has a pressure inside.

o Glomerular osmotic pressure opposites filtration - ~28 mmhg

Proteins aren’t being filtered. Therefore it’s making a

pressure. (see bulk flow)

o Net filtration pressure: ~17 mmhg. (can never be negative)

Glomerular filtration rate (GFR) – rate at which kidney is filtering.

Dependent on the net filtration pressure. ~125 ml/min

o GFR is autoregulated by the kidney.

o The diameter of the afferent arteriole changes

It constricts and reduces GFR. And vice versa.

GFR can be regulated using 2 ways

o Myogenic autoregulation

Increased blood pressure increases the outward pressure

against the sidewall of the arteriole. This causes the

artery to contract more.

It’s very effective, and maintains a normal GFR for all

blood pressures between 80 and 180 mmhg.

o Tubuloglomerular autoregulation

Increase in GFR is sensed by the macula densa cells in the

tubule.

The macula densa sends a paracrine signal to the afferent

arteriole to contract.

This causes decrease in GFR.

o Neural and hormonal control of the afferent arteriole.

For ex. epinephrine causes vasoconstriction.

Regulation of reabsorption in proximal tubules.

o Active transport: Na+ flows into the tubule. It is passively

transported into the epithelium cells in the tubule. It’s then

pumped using the Na/K pump into the interstitial space. The bulk

flow causes Na+ to go into the peritubular capillary blood.

o Secondary Active Transport: Glucose enters through a Symport

with Na+ ions. Na+ gradient provides energy for the glucose to

be pushed into the cell. It then diffuses out of the cell on the

other side.

In normal conditions, all glucose that is filtered is

reabsorbed.

With high blood sugar, all glucose can’t be reabsorbed

Glucosuria – pissing out glucose.

o Diffusion

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Urea can diffuse through membranes.

So a concentration gradient must be formed for it.

Active transport of NaCl from the filtrate into the

peritubular capillaries causes water to follow.

So the concentration of urea has gone up since water

concentration has gone down.

This way, urea goes back into the blood stream.

Secretion can be regulated as a renal process as well.

o Normally involves transport against a concentration gradient.

o It occurs in the PCT and the DCT

o It handles H+ and K+

Diabetes Mellitus – type 1

o Commonly autoimmune disease– destruction of β1 cells in pancreas

o Insulin hyposecretion or hypoactivity.

Person has to intake artificial insulin

o Hyperglycemia – elevated levels of plasma glucose.

Leads to glucosuria

This leads to polyuria (osmotic diuresis) – increases the

amount of urine produced

Polydipsia – you’re going to always really thirsty.

Polyphagia – you’re going to always be hungry.

Causes damage to blood vessels, eyes, kidneys, CNS, etc.

Type 2 Diabetes – 97% of all diabetics.

o Insulin resistance – inability to recognize proper levels of

glucose and get rid of it.

Skeletal muscles and all won’t really get glucose.

o Glucose tolerance test can find if they’re diabetic or not, but

they can’t differentiate between Type 1 and Type 2.

o Hyperglycemia – high blood sugar.

o If untreated, people will get atherosclerosis, renal failure,

blindness, neurological damage, etc.

o About 70% of people die from a cardiovascular disease.

Lecture 15 (3/15) (Cabot)

Kidneys can only converse fluid, not restore it

o GFR and urine regulation conserve fluid.

Na+ reabsorption is an active process.

o It’s not regulated in the PCT

o But in the collecting duct, it is regulated.

Water reabsorption

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Water reabsorption is by osmosis (diffusion) and will follow Na+

reabsorption (If possible)

o Water moves down its concentration gradient due to Na+

generating the gradient. (Na+ leaving makes water leave)

Na+ Reabsorption and Water reabsorption are independently regulated.

Water movement -

o Can only occur if epithelial cell membranes are permeable.

o H2O reabsorption is high in the PCT.

H2O and Na+ are reabsorbed in constant amounts in PCT.

o H20 permeability in the collecting duct can be high or low and

is physiologically regulated.

Hormonal control of H2O reabsorption

o In the hypothalamus are sensors that sense the osmolarity of

blood.

o If there’s an increase in osmolarity (decrease in water), urine

production is slowed.

AVP is released

It decreases the generation of urine by reabsorbing more

water.

AVP is (arginine vasopressin), also called ADH (anti-diarrheic

hormone) is a hormone released by the hypothalamus/pituitary gland.

o It stimulated by many things.

Changes in osmolarity, volume or pressure of blood

Also released due to angiotensin.

o It binds to the vasopressin receptors on the collecting tubule

cells.

Receptor is a G protein receptor that sends out a secondary

messenger, cAMP.

o cAMP facilitates the delivery of vesicles to the apical

membrane. The vesicles have aquaporin channels.

o Doing this increases the permeability of the membrane to water

More water will be reabsorbed.

Diabetes Insipidus – Has nothing to do with the other diabetes!

o H2O Diuresis – you piss out tons of water.(25L/day vs 1.8 L/day)

o Occurs When AVP secretion and/or receptors don’t work.

Water can’t flow through concentration gradient.

H20 diuresis is different from osmotic diuresis

o H2O diuresis is not due to excessive solute loss

o Osmotic diuresis is water loss due to excessive solute loss. .

Na+ reabsorption

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Na+ Excreted = Na+ filtered – Na+ reabsorbed

RAAS – Renin–Angiotensin–Aldosterone System.

The kidney can produce and store renin in the JG cells. It can also

release them at the right time.

RAAS Steps:

o Stimulus to generate renin release is severe drop in MAP.

o Decrease in MAP causes brain to try and increase MAP.

Renal sympathetic nerve synapses on the Granular (JG) cells

Cells will then release Renin

o The liver generates angiotensinogen all of the time..

Renin chops off a piece of the angiotensinogen and makes it

angiotensin I.

Angiotensin I is a biologically inactive peptide.

o Many epithelium cells in the body have ACE – Angiotensin

converting Enzyme.

It’s particularly high in the Lung capillaries (~40%)

It converts Angiotensin I to Angiotensin II

Angiotensin II is biologically active.

o Angiotensin II has 2 different effects

It has a powerful effect of vasoconstriction in the

cardiovascular system. Causes increase in MAP.

Will cause GFR to decrease due to afferent arteriole

constricting.

It causes the adrenal cortex to synthesize and release the

steroid hormone aldosterone.

Because steroid hormones can’t be stored due to being

lipophilic, they have to be made on the spot. This

takes a few hours.

o Aldosterone causes Na+ ion and water retention.

It affects the hypothalamus and causes release of AVP.

Aldosterone pathway:

o Aldosterone flows through the membrane and binds to receptors

inside the cytoplasm.

o The receptor-aldosterone goes into the nucleus and causes

protein production.

o 2 interesting proteins that are generated:

Increases synthesis/insertion of Na+ channels on the apical

(facing tubule) membrane.

Increases the permeability of the Na+ so it can be

reabsorbed so much.

Na+/K+ pumps are made. Na+ reabsorption increases a lot.

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Water flows with the Na+ out.

Renal Regulation of K+

o Most abundant intracellular ion. ECF conc. is regulated.

It’s critical to our survival.

o Important for maintain membrane potentials.

Processing of K+

o It’s filtered.

o It’s passively reabsorbed in the PCT.

o It’s regulated in the collecting duct.

Increases in plasma angiotensin & plasma potassium leads to more

aldosterone.

o Aldosterone makes Na/K pumps that cause K to be pumped into the

cell. It also increases K+ channels on the apical side.

Causes K+ to be excreted.

2 Conditions due to K+ concentrations:

o Hyperkalemia: too much K+ – depolarizes cells, can lead to

cardiac arrhythmias.

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Things that usually won’t reach threshold end up reaching

it.

Lethal – it’s what’s used in lethal injections.

o Hypokalemia: too little K+ - hyperpolarizes cells, can lead to

failure of respiratory and cardiac cells.

Graded potentials can’t reach the threshold due to

hyperpolarization.

Clearance – A useful way to measure renal function

o It’s a non-invasive way to measure GFR

o It’s defined as the volume of plasma from which a substance has

been completely removed per unit of time (“cleared”/time)

o It’s a rate.

o To measure GFR, you need a substance that’s filtered, but not

reabsorbed or secreted.

So filtered = excreted.

Inulin is this substance.

Process of clearance-

o Give someone an IV with inulin and measure how much you give and

what concentration. (let’s say the conc. Is 4 inulin per 100 ml)

o Inulin will get filtered at the GFR rate. (let’s say rate is

100ml/Min)

o Then you collect urine and analyze the rate. (so let’s say

there’s 4 inulin molecules. Then you know that GFR is 100ml/min)

o GFR = clearance of inulin.

If the clearance of a substance X is greater than clearance

of inulin, then it’s filtered and secreted.

If the clearance of a substance X is less than clearance of

inulin, then it’s filtered and reabsorbed.

If the clearance of a substance X is equal to clearance of

inulin, then it’s filtered, not reabsorbed, and not

metabolized.

Creatinine is the closest naturally occurring substance

with clearance values near those of inulin.

Lecture 16 (3/20) (Cabot)

Hormone – A chemical messenger secreted by a cell or group of cells

(neurons included) into the blood for transport to a distant target,

where it exerts its effects at very low concentrations.

o All hormones exert their effects through receptors.

Effects of hormones

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o Alter membrane permeability/electrical state

o Regulate the transport of molecules across membranes

o Activate genes for transcription

o Stimulate the synthesis of proteins or other molecules.

o Active or deactivate enzymes.

o Induce exocytosis (Secretion)

3 classes of hormones

o Peptide (for ex. insulin, AVP, angiotensin II, ACTH)

Most common

Short chains of amino acids.

Mostly hydrophilic & lipophobic. Easily transmitted in the

blood.

Most receptors are G Protein linked receptors.

Insulin receptor is tyrosine kinase.

o Amine (catecholamine) (ex. epinephrine, norepinephrine, thyroid)

All derived from the amino acid tyrosine.

Water soluble. They are Lipophobic.

Most receptors are α1 receptors. Also β1,2 receptors.

These are still G protein linked receptors.

o Steroid hormones (ex. aldosterone, cortisol)

Are derived from cholesterol.

They are hydrophobic and lipophilic. They don’t like being

transported through blood.

They have to be bound to a protein to be transported.

There’s no barrier to these cells.

Steroid receptors are intracellular in the cytoplasm.

They have a long half-life.

Peptides and catecholamines have a very fast response time. – minutes

to an hour.

Steroids have a

very slow

response time –

hours to days.

o But they

stick

around for

longer.

3 Classes of

stimuli for

hormone release:

o Humoral

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Plasma or ISF.

o Neural

o Hormonal.

Humoral stimulus pathway example:

o Rise in plasma glucose inhibits α cells in the pancreas and

stimulates β cells in the pancreas to release insulin.

o Increased levels of insulin affect the liver and other cells.

Liver cells get affected by insulin

Glycolysis, glycogenesis, and lipogenesis are

increased.

Muscles and adipose tissue increase glucose transport.

o All of this leads to decrease in plasma glucose.

About insulin

o Half-life of 5 minutes (very short)

o Factors affecting release: plasma glucose, GI hormones, nerves.

o Target cells: liver, muscle/adipose tissue,

Brain, kidney and intestines are not insulin-dependent.

They take up glucose without insulin. This means that

if you have too much insulin and not enough glucose in

the blood, the brain will be glucose deprived (faint).

o Target receptor: tyrosine-kinase receptor.

o Actions: Lower plasma glucose, by increasing transport and use.

Increases synthesis in the

cell.

Glucagon is a peptide hormone that

follows the same pathway.

o It is released when α cells in

the pancreas are stimulated.

Happens when glucose levels

get too low.

Also, β cells are inhibited

from releasing insulin.

o Liver will then generate glucose

Gluconeogenesis and

glycogenolysis.

o Plasma glucose increases and you

get back to normal.

About glucagon

o Has a short half-life. 4-6

minutes.

o Stimulated by low plasma levels.

o Targets liver.

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o Receptor is G protein-coupled adenylate cyclase with cAMP.

o Actions: gluconeogenesis and glycogenolysis in liver.

Neural Stimuli. Example pathway – autonomic, insulin.

o Autonomic system sends an impulse down to a parasympathetic

ganglion, where it synapses and continues to the pancreas. The

pancreas then releases insulin.

Adrenal medulla pathway (sympathetic neural stimuli)

o Preganglionic sympathetic neuron synapses in the adrenal

medulla’s Chromaffin cells (wannabe neurons).

They have nicotinic acetylcholine receptors.

Channels open and the Chromaffin cell depolarizes, causing

ca2+ channels to open.

Ca2+ causes exocytosis of vesicles containing epinephrine

and some norepinephrine.

NE is both a neurotransmitter and a hormone.

E/NE bind to arteriolar muscle contraction (α receptors)

and bronchiolar smooth muscle relaxation (β receptors).

Neural control of hormones that release hormones etc. hypothalamus.

o Hypothalamus and pituitary gland are connected by neurons and

vasculature via the

pituitary stalk (called

infundibulum)

Pituitary gland has 2 parts

o Posterior gland is neural

tissue.

o Anterior gland is true

endocrine tissue.

Posterior pituitary gland:

o Has 2 hormones that it

releases:

o Oxytocin and AVP/ADH(See

kidney).

Oxytocin is used for

uterine contraction.

o Hormone is made and package

in cell body of neuron in hypothalamus. (green neurons in pic)

o Vesicles containing hormone are stored in posterior pituitary.

When you’re drunk, you have to take a long piss. This is cause

alcohol inhibits AVP release.

Neurotransmitter is short distance. Neuralhormone is long distance.

Hormonal Stimuli – complex endocrine pathways. AKA Hormone-ception.

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o Stimulus causes hypothalamus to secrete a hormone. The hormone

causes an endocrine gland to release another hormone, which then

does the work.

Hypothalamus releases a hormone (Called a releasing

hormone) into a capillary bed called the median eminence at

the base of the hypothalamus.

This then goes to capillary bed of the anterior pituitary.

Anterior pituitary then releases the main hormone.

Capillary bed to capillary bed is called portal

circulation (connected via portal vessels)

Then this hormone can cause a release of another

hormone

o There are 6 anterior pituitary hormones.

CRH(Corticotrophin releasing hormone) Pathway (AKA stress pathway) :

o Stress causes CRH to be released from the hypothalamus.

o CRH is released into the capillaries of the median eminence. It

then passes through the portal vessels into the capillaries of

the anterior pituitary.

o CRH will cause the Anterior Pituitary to release the peptide

hormone ACTH – adrenocorticotropic hormone) into the blood.

o ACTH will then bind to receptors in the adrenal cortex. Adrenal

cortex increases production of the steroid cortisol, which takes

a while to happen.

o Cortisol will then enter the blood stream. It causes increase in

blood glucose.

Cortisol is a glucocorticoid.

It promotes gluconeogenesis

Leads to hyperglycemia

Protein catabolism

Increases energy metabolism by mobilizing fat stores.

Depresses inflammatory and immune responses.

Vasoconstriction.

o Regulation: (negative feedback)

Increased levels of cortisol lower production of CRH and

ACTH. (long loop feedback)

ACTH levels also regulate CRH levels too. (short loop)

About Cortisol –

o Steroid that is made from cholesterol.

Must be transported on binding globulin protein in blood.

o Half-life is 60-90 mins.

o Target receptor is intracellular (because it’s a steroid)

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Giving external steroids reduces production of cortisol

o If this is prolonged, the cells that produce CRH/ACTh/cortisol

producing cells die.

Cushing’s syndrome: when you have too much cortisol production.

o You get a moon face with red cheeks.

o A buffalo hump – fat deposits on the shoulder.

o Hypertension due to vasoconstriction.

o Increased abdominal fat.

o Easy bruising and poor wound healing.

Physiological responses to stress:

o Rapid response (HypothalamusAnt. Pit. adrenal cortex E/NE)

Increased CO, redirect blood flow, maintains BP

Maximized breathing

Increased sweat production.

Mobilizes carb and fat stores.

Increases glucose production and inhibits insulin.

o Prolonged response (CRHACTHCortisol)

Glucocorticoid response (cortisol)

Immunosuppression.

Fat breakdown.

Mineralocorticoid response.

Retention of sodium and water by kidney

BP will increase due to AVP & Angiotensin II.

------------------------ End Midterm 2 Material --------------------------

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------------------------ Begin Midterm 3 Material ------------------------

Lecture 17 (3/22) (Cabot) – Innate Immunity

Immunology – study of physiological defenses by which the body

defends itself against foreign matter.

Components of

White Blood cells (leukocytes) arise from stem cells

o Lymphoid stem cells give rise to lymphoid white blood cells-

NK Cells

B cells

T cells

o Myeloid stem cells give rise to everything else

RBCs and platelets

Monocytes

Neutrophils

Eosinophils

Basophils

Most of the lymphoid cells aren’t circulating in blood, but rather

sitting in the interstitial fluid and lymph organs

Other cells that make up the immune system:

o Macrophages (different from monocytes)

o Dendritic cells (like macrophages)

o Mast Cells (different from bone marrow cells)

Lymphoid organs are where the cells reside and mature

o Primary organs: Where the cells mature.

o Secondary organs: Where mature lymphocytes reside and replicate.

2 main immune organs:

o Bone Marrow: B and NK lymphocytes mature here

o Thymus: T lymphocytes mature here.

Secondary organs can be encapsulated or unencapsulated

o Spleen and lymph nodes are encapsulated.

o Tonsils and Gut-associated lymphoid tissue (GALT) are not.

Immunity can be divided into innate and acquired (adaptive) immunity.

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Innate system is what we’re born with.

o It’s non-specific.

o Response time is minutes to hours.

o Clears or contains an infection till acquired response happens.

External defenses: skin, mucous membranes, secretions.

Internal defenses:

o Natural killer (NK) cells – kills virally infected or cancerous

cells.

o Inflammatory response

o Fever.

Phagocytes – they carry out phagocytosis.

o They’ll recognize something on the surface of the bacteria, and

then swallow it (endocytosis), and then merge with a lysosome,

which kill and digests the bacteria.

o They recognize bacteria based on carbs and lipids on the cell

walls. Also, tagging by the use of opsonins also helps

recognize.

Antimicrobial proteins

o Complement – a series of 30+ proteins activated in a sequence.

When they come in contact with the bacteria, they make

holes in the wall of the bacteria, causing water and ions

to flow in, thereby bursting the bacteria.

This is called the Membrane Attack Complex (MAC)

Opsonin – chemical mediator that binds to and tags a

microbe to promote phagocytosis.

Antibodies

Complement proteins. (called C3b)

o C3b acts as a ligand and triggers receptor

mediated phagocytosis in macrophages.

o Interferons –

It’s a cytokine – it affects the growth and activity of the

microbe

It prevents replication of viral cells when they take over

host cells.

Infected cells will generate these.

o Natural Killer Cells –

Has surface receptors that bind directly (but

nonspecifically) to virus infected cells and cancer cells.

Releases chemicals that induce apoptosis (cell death)

Inflammatory response – Happens when skin/barrier is broken

o 4 signs: Swelling , Heat, redness, pain.

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o Damaged cells and responding cells release chemicals

o Leads to vasodilation and increased vascular permeability.

o Chemicals cause the neutrophils in the blood to bind to the

endothelial cells in the blood vessels.

o Diapedesis- the cell squeezes out of the vessel.

o Chemotaxis – cells move towards the infected cells via chemicals

Fever –

o Most pathogens don’t replicate well in high temperatures

o It enhances phagocytosis and a bunch of other immune stuff.

Lecture 18 (3/27) (Cabot) – Acquired Immunity

Acquired response is slower, but it has memory and specificity.

o Memory doesn’t last forever, but lasts for a long time.

Humoral immunity – recognizes and destroys antigens in the ECF.

o B cells, antibodies, opsonins, and macrophages.

Cell-mediated immunity – destroys antigens hidden inside cells.

o Helper(CD4) and cytotoxic (CD8) T cells, NK cells.

3 stages of immune response

o Encountering and recognizing an antigen by lymphocytes

o Lymphocyte activation

o Antigen destruction

Antigen –

piece of the

microbe that

is recognized

by the

system.

B cells and T

cells

receptors

bind to

antigenic

determinants.

o Receptors are very different for each one. Look at picture.

o Each cell identifies one type of antigen but has 100k receptors.

B Cell Activation

o B cells binds to antigen molecules.

o B cell keeps replicating itself. This is called clonal selection

o Clones can attach to other antigens of the same type now.

o B cells differentiate in 2 different types once they’re done.

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Memory – clones go back to the humeral space to chill.

Plasma cells – cells that eject antibodies(the receptors)

into the plasma

o This way, the next time the infection happens, the response is

faster and more robust.

The point of multiple immunizations.

Antibodies do lots of things.

o They act as opsonins, the constant part (bottom part) acts as a

receptor for macrophages. This leads to phagocytosis.

o Antibodies help initiate the complement process, which create

the MAC.

o Antibodies clump and immobilize the antigens

o They neutralize viruses by surrounding and attaching to it.

T Cell Activation

o T cell receptors are 2 chained proteins embedded in the membrane

Are very different from the B cell receptors .

o T cell receptors cannot combine with an antigen unless the

antigen is first tagged with some of the body’s own proteins.

o Major Histocompatibility complex (MHC) proteins are the proteins

that the cell expresses.

MHC class I proteins are on the surface of all cells.

Except RBCS

The MHC proteins hold a piece of cut up protein from the

cell.

o T cells are born in the bone marrow, mature in thymus, and then

chill in the secondary lymphoid organs.

Cytotoxic T cell (CD8) activation

o They wander through the ECF looking at the surfaces of cells

looking for the MHC and the attached antigens.

If they find an MHC protein with virus dna on it, they’ll

respond.

CD8 is the protein on the T cell that recognizes the MHC I.

o The T cell will release 2 types of paracrine molecules

Perforins – they punch holes in the membranes of the cell.

Enzymes – they go inside the holes and activate apoptosis.

o The T cell also clones itself a bunch of times, and some go to

storage.

MHC II proteins are found only on the surface of macrophages, B

cells, and dendritic cells. These cells are called APC cells

(antigen-presenting cells)

o MHC II proteins will show the chopped up antigen peptides.

o But cytotoxic T cells won’t respond. Helper T cells will instead

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Helper T cells use CD4 to recognize MHC II.

o Helper T cells help facilitate the response to the antigens.

They outnumber cytotoxic T cells by more than 2:1.

Helper T cell activation

o APC cells and Helper T cells match up with both the MHC II

complex, and another non-antigenic receptor.

o When this happens, the APC releases paracrine signals.

o The Helper T cell becomes activated and goes around activating

other responses.

o Activated Helper T cells can activate and help B cells.

They are needed for B cells to function normally.

o Activated Helper T cells also stimulate/activate cytotoxic T

cells.

Innate and Acquired (humoral and cell mediated) act synergistically

together.

Immune system failures

Autoimmune diseases – incorrect immune response

o Type 1 diabetes

o Myasthenia gravis

o Multiple sclerosis

o Lupus

o Rheumatoid arthritis.

Overactive responses

o Allergic reactions. Can be lethal.

Lack of response

o Immunodeficiency diseases – Primary or acquired

o AIDS is an acquired immunodeficiency diseases.

HIV/AIDS.

o HIV is an asymptomatic infection

o AIDS is basically destruction of the immune

system.

o Routes of transmission

Transfer of contaminated blood

Unprotected sex

Contaminated needles

Mother to fetus/child (Placenta or

breast milk)

HIV is a retrovirus that has reverse

transcriptase.

Process-

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o Virus fuses with the cell and the capsid (outer shell) proteins

are removed.

o Reverse transcriptase helps synthesize a DNA strand that’s got

the viral RNA.

o Virus uses cell machinery to produce lots of copies of itself,

and then sends them out to infect some more.

HIV/AIDS Timeline:

o Virus infects and enters the

body, but lays dormant for 6-

8 years.

o After 6-8 years, it comes

back and destroys the immune

system by infecting the

Helper T cells.

Less Helper T cells,

means less activation of

CD8 cells and B cells.

o This leads to AIDS.

o AIDS leads to infection by

other regular microbes.

o This leads to death.

AIDS treatment strategy

o Drugs that prevent fusing of

the HIV virus to the CD8

cells

o Block Reverse Transcriptase

from transcribing viral DNA.

o Block Integrase from chopping up the nuclear envelope and

allowing Viral DNA from being inserted inside.

o Block HIV Enzymes from reassembling and activating the viral

DNA.

HAART – Highly active anti-retroviral therapy.

o Cocktails of all of the aforementioned drugs.

o It lets HIV infected individuals live a long time.

Lecture 19 (4/10) (Collins) – Respiratory System

Main function of respiration is gas exchange. O2 in, CO2 out.

o Animals need a constant supply of O2 and let off CO2.

O2 is not very soluble in water.

Respiratory surface – site of O2/CO2 exchange.

o They must be moist – the gases dissolve in the water before

exchange happens.

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o Large surface area is needed.

Humans have 50-100 square meters of surface area in lungs.

How Animals achieve large surface area:

o Small organisms can use the entire surface area of the organism

O2 diffuses very slowly through water

Cells must be within ~1mm to the respiratory surface.

o Larger animals use specialized respiratory surfaces.

Not all animals transport the gases via circulation though.

o Tracheal systems – lots of trachea go throughout the body

Trachea get smaller and smaller, untill they’re close to

every cell in the body.

Gases don’t go in circulatory system.

Rhythmic body movements compress and expand the tubes.

Insects use this.

o Coupled Respiratory & Circulatory System

Circulatory system acts as a transport system for gases.

Step 1 – exchange b/w respiratory medium and circulation

Step 2 – exchange b/w circulation and interstitial fluid.

o Aquatic Animals-

Water helps respiratory surfaces stay moist

But because of water, the O2 concentration is very low.

Therefore, exchange has to be very efficient.

o Gills –

Out foldings of body surface.

Can be all over body, or localized

Some are external (sea fish) others are internal

(lobsters)

Exchange is maximized by:

Ventilation

o Usually due to muscle movement. Energy is spent.

o For ex. paddle like appendages to push water over

gills. (Lobsters)

o Swimming increases water flow over gills.

Called Ram ventilation.

Counter-current exchange.

o Water flows through lamella (flaps that make

small channels in the gills),

o The lamella have a dense network of capillaries

o Blood flows in opposite direction of water.

o Terrestrial animals

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Advantages of Air – high conc. of O2. Fast diffusion.

Disadvantages – loss of water due to evaporation.

Temporal counter current exchange minimizes loss.

Gills and all wouldn’t work because they would dry up.

They must have an internal tube system.

Lungs – mammals and birds rely exclusively on them.

o Restricted to one location.

o Not in direct contact with other parts of the body.

Circulation system serves as the link.

o They have a dense network of very thin capillaries.

o Know basic anatomy of the lung – bronchi, alveoli, etc.

o Dead space – air that can’t really be used. For ex. air that was

already in your lungs when you inhale.

Lungs are inside a pleural sac

o They are stuck to the pleural sac due to pressure differences.

There’s less pressure in the sac than the lungs.

If pressure in pleural sac becomes too high you get

pneumothorax (collapsed lung)

Air flow depends on differences in pressures

o Air flow is proportional to ∆ pressure/resistance to flow.

o ∆Pressure = intrathoracic pressure – air pressure.

o Mammals exhibit negative pressure breathing.

∆Pressure is negative during inspiration.

Lower pressure inside than outside. So air flows in.

Inspiration is an active process

o Diaphragm expands the volume of the thoracic cavity, causing the

pressure inside to decrease. This causes air to go inside lungs.

o Exhalation is passive because the muscles relax and therefore

the thoracic cavity goes back to normal.

o Only when you’re doing very strenuous exercise does exhaling

become active.

Lung Volumes

o Dead space – air trapped in the airways at the end of each

breath (~150ml)

o Expiratory reserve volume – everything you can push out

o Inspiratory reserve volume – maximum intake

o Tidal volume – what you normally breathe. (~500ml)

o Vital Capacity – maximum volume of air that can be moved into or

out of the respiratory system with one breath.

o Residual Volume – volume of air remaining in lungs at the end of

a forced exhalation (~1200ml)

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Lecture 20 (4/12) (Collins)

Alveolar ventilation – volume of fresh air reaching alveoli per min.

o Alveolar ventilation = (breath volume – dead space)*breaths/min.

o Pulmonary ventilation is same thing, without dead space being

subtracted.

The lungs obey Fick’s law of diffusion

o Rate of diffusion = Coefficient * (C2-C1)

o Concentration gradient (C2-C1) is driving force.

Concentration of a gas is measured using partial pressure.

o Partial pressure = (percentage) * Total pressure.

o Ex. O2=21%, Tot. Pressure = 760mmhg. Partial p.= (.21)*760mmhg.

o Gases diffuse from regions of high partial pressure to low

partial pressure.

Partial pressure in a fluid is the

partial pressure of the same gas in

the air directly above the fluid.

When it comes to partial pressure in

fluids, solubility must be taken

into account.

o Not a good way to measure

amount of gas dissolved in

water.

O2 & CO2 exchange

o Gas exchange occurs only in the

capillaries.

o Inhaled air and alveolar space

air are different because of

mixing with dead space air. It

also equilibrates with the

pulmonary blood.

o Must be able to

compare/contrast the partial

pressures.

o Partial pressure of O2 at rest

is 40 mmhg, and can be lower

for very active tissue.

Oxygen is not very soluble in water

o So respiratory pigments are

used to carry the blood.

o Hemoglobin is the respiratory

pigment for mammals.

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o Some other animals use hemocyanin, which uses copper instead.

Hemoglobin

o It has 4 subunits, each with a heme group containing iron.

2 α subunits and 2 β subunits.

Each subunit can bind 1 molecule of O2, so 4 in total.

o Hemoglobin carries 98% of the O2 in the body.

Determines O2 carrying capacity in the blood.

Oxygen-Hemoglobin Dissociation Curve (sigmoid curve) (Important!)

o X axis – partial pressure of oxygen

o Y axis – oxygen saturation of hemoglobin

NOT oxygen concentration or oxygen content in blood!

This is the percent of the binding sites of hemoglobin that

are holding oxygen.

o When a red blood cell goes in the

pulmonary capillaries, and the O2

partial pressure is over 100 mmhg

(normal breating), you completely

fill the blood w/ oxygen.

o In the systemic circulation, a

bunch of things.

If tissue is at rest, O2 is

at 40 mmhg.

So it releases 25% of

the oxygen. So 1 out of

4 iron drops an O2.

If tissue is really active

and mmhg of O2 is at 10 mmhg,

It will release over 80% of its O2.

o This is a sigmoid relationship –

Molecules that carry multiple amounts of

same thing exhibit this.

Hemoglobin responds to the needs of

the tissue based on mmhg of O2.

pH will affect the hemoglobin and cause a

shift in the curve

o This is called the Bohr shift.

o Additional O2 released from hemoglobin

when pH is low (normal pH is 7.4)

o Increase in temperature will also shift

the curve to the right.

o Increase in partial pressure of CO2 will

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also cause a shift to the right.

All of these three things change when cells are active.

o Active cells will cause local changes in tissue that cause

hemoglobin curve to shift to the right, and release more O2.

Myoglobin – Respiratory pigment in muscle

o Has a single heme group, unlike hemoglobin

o Made by striated muscle, like the heart.

o Cells that have a lot of it appear red.

o It has a very high affinity for oxygen.

o It doesn’t leave the muscles.

o It has an exponential curve because it only

has 1 binding site.

o It acts as a reserve source of oxygen for

muscle.

It doesn’t release much oxygen until the pressure falls

below 20 mmhg.

o It gets its oxygen from hemoglobin. (Hb = hemoglobin in picture)

Bicarbonate Buffer system

o CO2 is very soluble in

water (blood)

o CO2 combines with water to

become carbonic acid

o The carbonic acid becomes

bicarbonate and H+

Catalyzed by carbonic

anhydrase

o 70% of CO2 becomes

bicarbonate

o 23% becomes bound to amino

groups, as in hemoglobin.

o 7% actually dissolves in

the water.

o Cl- moves into the RBCs

when bicarbonate leaves the

RBC (bicarbonate chills in

plasma)

Make sure you know EVERYTHING on

the massive summary picture on the

right

Respiratory Drive.

o Physiological drive to breathe

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o Factors affecting depth and rate of breathing

o PO2, PCO2, pH

o Emotions

o Sleep

o Lung inflation

o Light and temperature

o Speech

o Conscious Volition

Control of Respiration

o Everything is controlled by the Central nervous system

o Pons – Modulates rhythm.

o Medulla – Generates rhythm

Hering-Breuer stretch reflex

o Responds to the stretch of the lungs when inhaling

o Sensory info is fed to the medulla, which inhibits inspiration.

So inspiration stops inspiration.

o It’s not a very strong reflex.

Peripheral Chemoreceptors play a much larger role.

o They sense PO2 and PCO2 levels.

o They are located in close proximity to the large vessel leaving

the heart. (Aorta)

They are in the carotid body and aortic arch in humans

o They aren’t very sensitive to changes. They only respond to

extremes.

Central Chemoreceptors control breath to breath respirations.

Avian Respiratory System

Birds have more efficient respiratory systems.

Gas transfer takes place in small flow through tubes called

parabronchi.

The volume of the lung doesn’t change, unlike mammals.

Ventilation is achieved by compressing air sacs

o Air sacs reduce density of bird, so it makes it easier to fly.

During inspiration, the bird’s air sacs expand, which pull the air

into the lungs and air sacs.

During expiration, the air sacs compress, and it forces the air out

through the lungs and outside.

Air is exchanged in the parabronchi during both inhalation and

exhalation

Air flow through the lungs is unidirectional due to aerodynamic

valving (pressure differences force air into lungs)

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Lecture 21 (4/17) (Collins) – Regulation of Respiration

Medulla is the main source of respiration. It has 2 major respiratory

centers

o Dorsal group – inspiration – generates rhythm

Contains the central chemoreceptors.

o Ventral group – expiration.

Central chemoreceptors are extremely sensitive to changes in pH.

Capillaries at the blood-brain

barrier don’t let anything that

has a charge or polarization to

go through.

o So H+ can’t go through.

H+ is produced in the CSF due to

increase in CO2 that crosses

through the blood-brain barrier.

o H+ changes in the CSF can

change the pH dramatically

o Decrease in pH is sensed by

the medulla, and rate is

increased.

In order for O2 to cause

changes, the partial pressure of

O2 needs to be below 60 mmhg in

the aortic arch (normal is ~100)

o This is rare- respiratory

drive is primarily controlled by CO2 levels.

Shallow Water Blackout –

o Medical symptoms - Sudden loss of consciousness, amnesia, and

happens without warning

o Strikes typically happen within 15 feet of the surface.

o Physiological mechanisms for

shallow water blackout –

Hyperventilation blows

off CO2, increases pH of

CSF, and decreases

respiratory drive. O2

levels remain the same

O2 remains the same

because it’s based

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on hemoglobin, which is almost always full anyway. O2

isn’t very soluble in blood.

Hypoventilation leads to O2 drop, and huge CO2 increase.

This increases the respiratory drive.

This leads to the

breath hold time to

decrease.

o Hyperventilation makes it so

that it takes CO2 longer to

rise to the point where it

doesn’t trigger the urge to

breathe, prior to the O2 level

reaching the blackout zone.

o On ascent from free dive, lungs re-expand and O2 pressure in the

lungs decrease.

Near surface, the driving force for O2 exchange approaches

zero.

Physiology of diving mammals and birds

o Animals with lower rate of O2 use can dive for longer periods of

time (low metabolism)

Either having it low normally (turtles) or reducing it.

o Diving animals have significantly increased oxygen capacity –

Difference is minimal with lung capacity. Most of the

storage is done in the blood and muscle the most.

o Diving reflex – neurological response due to water splashing on

face

Vasoconstriction – peripheral blood flow is restricted.

Redirects blood to brain and heart.

Bradycardia – heart rate and cardiac output drops.

Lowers metabolism and O2 demand.

Lecture 22 (4/19) (Collins) - Digestion

Heterotroph – an organism that obtains organic food molecules by

eating other organisms or their by-products.

Dietary needs

o Chemical energy for cellular work

o Organic precursors – for biosynthesis

o Essential nutrients – substances animals cannot make.

Chemical energy – obtained from oxidation of organic molecules

o Fats, carbohydrates, and proteins

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o Fats release twice as much energy than carbs and proteins.

o Fats and carbs are preferred.

Fats –

o Very lipophobic molecule.

o Fats compose of a glycerol carbon backbone with up to 3 fatty

acids connected via ester linkages

o Saturated fats are carbon chains full of hydrogen, that have no

double bonds between carbons. The chains are very straight

They are solid at room temperature (Such as butter)

o Unsaturated fats aren’t straight, and can’t pack together, and

therefore are liquid at room temperature.

Animals are unable to make unsaturated fatty acids.

o Animals can easily use cis fats, but not trans fats

Trans fats are synthesized in factories, cis by animals.

Carbohydrates

o Carbs are all composed of glucose molecules. They are linked

between the 1 group and 4 group, called a 1-4 linkage.

o There are 2 major forms of carbs – starch and cellulose

o α 1-4 linkages create starch. It can easily be digested by us.

The hydroxyl groups are all in the same plane.

Starches create helical structures.

Plant starch is very simple compared to animal starches.

o β 1-4 linkages create cellulose. We can’t digest it.

The hydroxyl groups alternate side to side.

The structure of cellulose is very linear, and it can band

together in large strands.

It’s used for strength and structure. Ex. cell wall.

Proteins

o Amino acids join together to create a back bone composed of a

nitrogen and 2 carbons that have side groups hanging off.

o Structure

Primary – string of amino acids

Secondary – α helix or β pleated sheet

Tertiary – 3d functional protein

Quaternary – multiple protein subunits come together to

make one massive protein (ex. hemoglobin)

Organic precursors – we need sources of carbon and nitrogen.

Essential nutrients – things we can’t make

o Some amino acids

There are 8 we can’t make. (know them!)

Methionine

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Valine

Threonine

Phenylalanine

Isoleucine

Tryptophan

Lysine

o Essential Fatty acids

Deficiencies are rare, but there’s one we depend –

Polyunsaturated fatty acids (PUFAs) – needed to make

membrane phospholipids

Animals cannot make omega-3 and omega-6 PUFAs.

o Vitamins

Can be water soluble or water insoluble

Soluble vitamins can be ingested a lot, transported to

wherever it needs to go to the body, and then get pissed

out. For ex. Vitamin C

Know everything on the table!!

Fat soluble vitamins (A,D,E,K).

They enter the fat and stay in the fat for a long

amount of time.

Greater toxicity risk.

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o Minerals

Inorganic nutrients

Metallic elements involved in protein structure

For ex. calcium, NA, K, CL, iron, and iodine.

Four stages of food processing

o Ingestion – eating

o Digestion – breaking food down into molecules small enough to be

absorbed

o Absorption – cells take up small molecules

o Elimination – removal of undigested material

Digestion occurs in specialized compartments –

o Intracellular digestion

o Extracellular digestion

Gastrovascular cavities & alimentary canals

Intracellular digestion, Ex. Paramecium

o Specialized ingestion through oral groove via pinocytosis

o Food is immediately put in a vacuole

o Digestion and absorption happens in the vacuole

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Digestive enzymes secreted in

o Exocytosis at the anal pore.

Gastrovascular cavities –

o Allows for larger things to be ingested.

o Has a single opening to the outside

o Ingest food via mouth, and digest it inside the cavity.

o Absorption is also done in cavity, and then it is eliminated

through the mouth.

Alimentary Canal

o Tubes that extend between two

openings (e.g. mouth Anus)

o Food moves in one direction (few

exceptions)

o Specialized regions for digestion

and absorption in steps.

Most absorption is done in the small

intestine.

GI tract (The whole tube) is lined

with strong smooth muscles.

Stomach has very acidic secretions.

Intestines have very basic secretions.

Lecture 23 (4/24)

(Collins)

Know everything in

the picture

We start digesting

food both

mechanically and

chemically in the

oral cavity.

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Tongue forms a ball (bolus) and pushes it back.

Saliva produced by the salivary glands begin starch breakdown.

Pharynx/esophagus conducts the food to the stomach.

o There is striated muscle at the top of the esophagus (voluntary

control)

o There is smooth muscle in the lower esophagus.

o Involuntary waves of contractions move food bolus to the stomach

Called Peristalsis.

Stomach is a large elastic organ

o Animals don’t have to eat constantly thanks to stomach

o It does the initial digestion of protein

Hydrochloric acid and pepsin (stomach pH 2)

Mixture of these 2 is called gastric juice

o Mechanical churning of food.

o Lining of stomach has thousands of gastric pits that have cells

Mucus cells – protects the epithelium cells.

Parietal cells – secretes hydrochloric acid.

Chief Cells – Produce pepsinogen.

o Pepsinogen is an inactive proenzyme

It is synthesized as an inactive enzyme.

It is converted to active form as needed.

When HCl meets the pepsinogen, it activates it into pepsin

Pepsin can also activate pepsinogen (positive feedback!)

o The acid in the stomach does a lot of things.

It disrupts the ECM that holds cells together

Denatures (unfolds) proteins

Kills most bacteria and pathogens.

o Smooth muscles mix the bolus with the gastric juice, to create

what’s called acid chyme.

o Contractions push the acid chyme through the pyloric sphincter

into the small intestine.

Small Intestine

o Longest part of the intestine. Approx. 6 meters long.

o Major organ of digestion and absorption

Major site for enzymatic hydrolysis and nutrient absorption

3 Major Parts: Duodenum, Jejenum, and Ileum

Duodenum

o Short first part of small intestine. (~25cm)

o Acid chyme mixes with digestive juices.

o Digestive Juices come from multiple sources

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Pancreas, liver/gallbladder, and gland cells all meet in

the duodenum.

o Pancreatic Secretions

Bicarbonate –

neutralize acid

chyme (increase pH

to 7-8)

Peptidases –

Protein digestions

Nucleases -

hydrolyze DNA &

RNA

Amylases – Carb

digestion

Lipase – fat

digestion.

The pancreas is both exocrine and endocrine.

o Pancreatic peptidases – go from inactive to active like pepsin.

Trypsinogen trypsin

Procarboxypeptidase carboxypeptidase

Chymotrypsinogen chymotrypsin

The duodenum has a membrane bound enteropeptidase

This is what activates trypsin

Trypsin activates the other two, as well as itself.

o Liver secretes Bile

Bile is made by the liver, but stored in the gallbladder.

Bile contains bile salts and bile pigments.

Bile salts are composed of cholesterol and amino acids.

The salts break up the fat globs into small pieces.

This facilitates hydrolysis of fat by the enzyme lipase.

Jejunum & Ileum

o Jejunum is the major site of digestion and absorption.

o It has a very large surface area due to -

Large circular folds into the lumen.

Finger like projections called villi.

The epithelial cells on the villi have their own

projections, called microvilli. Microvilli = brush border.

o Nutrients are absorbed through the epithelial cells in the

villi.

The nutrients are then transferred to either the

circulatory and lymphatic systems.

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Sugars and amino acids go to the circulatory system

o The circulatory veins go through the hepatic

portal vein to the liver before the heart.

Fats go to the lymphatic system via lacteals, and then

into the veins ultimately.

o Fatty acids and glycerol and cholesterol are

assembled in the epithelial cells to make

chylomicrons.

o The chylomicrons then go into the lacteal.

o The Ileum absorbs whatever the jejunum doesn’t.

Regulation of digestion

o Stomach releases gastrin

Food in stomach or parasympathetic nerves stimulate release

Gastrin causes secretion of gastric juices.

Gastrin is inhibited if the pH becomes too low.

o Secretin – secreted by cells in the wall of the duodenum

Secreted in response to low level of pH of acid chyme

It stimulates the release of bicarbonate from the pancreas.

o Cholecystokinin(CCK) – also secreted by duodenum wall cells

Secreted in response to amino acids & fatty acids

Stimulates release of pancreatic enzymes.

Causes contraction of gallbladder (releases bile)

o Enterogastrone is also secreted by wall cells.

It inhibits stomach motility and gastic acid secretion in

response to fatty acids in the duodenum

It effectively tells the stomach to stop/slow down while

the duodenum takes care of the fatty acids.

Large Intestine

o Has a pouch called a cecum, to which the appendix is attached.

o By the time things reach the large intestine, 99% of the

nutrients have been

absorbed. So everything in

there is waste + water

o Main purpose of large

intestine is reabsorption

However, most of the

water occurs in the

small intestine.

Water Reabsorption

o Get to know the chart on

the right very well

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Evolutionary Adaptations

o Vegetation is more difficult to digest.

o Herbivores and omnivores tend to have longer canals.

More time and surface area for digestion.

o They have really big cecums

Fiber enters in the cecum, which is full of symbiotic

organisms that break down the cecums.

Symbiotic organisms – microorganisms such protists and bacteria

thrive in fermentation chambers in herbivores

o They provide essential nutrients, digest cellulose, and can be a

direct food source as well.

Lecture 24 (4/26) (Collins) – Locomotion and motor control.

Locomotion – active travel

o Purpose – searching for food, escaping from danger, mating.

o Requires energy to overcome friction and gravity.

As animals get larger, locomotion gets more efficient.

Swimming

o Swimming is the most efficient form of locomotion

o The major challenge is overcoming the resistance of water

Water is more dense than air, and a sleek shape is a common

adaptation.

o Overcoming gravity isn’t much of a problem because animals have

some buoyancy.

o Animals swim in diverse ways

Using legs(insects)

side to side body/tail movement (fish),

Jet propulsion – sucking water in and squirting it out

Squids, etc.

Locomotion on land

o Primary challenge is overcoming gravity.

o Overcoming resistance of air is a minor problem

o Strong muscles and skeleton more important than a streamlined

shape

Flying

o It’s more efficient than ground locomotion.

o Overcoming gravity is the major problem

o The shape of wings provides lift.

Skeletons

o Functions – support against gravity, maintain form and shape,

protection, and movement

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o Three types of skeletons

Hydrostatic skeletons

It’s fluid held under pressure in a closed compartment

It’s well suited for aquatic animals and provides

support for crawling/burrowing in terrestrials.

Water is heavy however, and it’s not very protective.

Animals with this skeleton move by contraction of

muscles against a relatively non compressible fluid.

Example – earthworm

o Made up of repeating segments. Each segment is a

sack of coelomic fluid.

o Antagonistic circular and longitudinal muscles

are coordinated to move it. (peristalsis)

o

Exoskeletons

Hard encasement on the surface of an animal

2 major categories

o Mollusks such as clams

Calcium carbonate shell that keeps growing

o Arthropods such as lobsters

Jointed skeletons made up of chitin

Exoskeleton is shed and replaced.

Endoskeletons

Hard supporting elements buried inside soft tissue

Chordates – cartilage and bones

Provides support and increase mobility, as well as

protection.

Muscle Movement

o Movement is based on contraction of muscles against skeleton

Muscle movement is always to contract

Extension is passive.

o Muscles work in antagonist pairs – they work against each other

in opposite directions to move body parts.

o Skeletal muscle fibers generate tension by shortening(sarcomere)

o Each action potential in the motor neuron produces a twitch

contraction in all of the muscle fibers innervated by that motor

neuron.

Muscle fibers are slaves to the neuron that controls it.

o The time source and amount of tension generated is determined by

the properties of the muscle fibers.

Muscle Tension

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o There are two ways that tension generated can be varied

Temporal summation – vary the tension generated by an

individual muscle fiber

This is done by changing the frequency of the signal

being sent.

Recruitment – vary the number of motor units (muscle

fibers) that are activated.

o Fatigue – some muscles can only maintain max tension for a short

amount of time, while other muscles are fatigue resistant.

Temporal Summation

o A second action potential before the muscle relaxes from the

first one will cause an addition to the tension of the muscle.

o Increasing the frequency of action potentials increases the

amount of summation and therefore tension of the muscle.

o Tetanus – when you reach the maximum summated twitch due to high

frequency of action potentials.

Muscle fatigue – inability to maintain tension during periods of

sustained, repetitive activation.

o Muscles that use anaerobic metabolism fatigue due to lactic acid

accumulation

o Muscles that use aerobic metabolism don’t fatigue.

Motor unit recruitment

o The strength of contraction can be increased by activating

additional motor units

o A motor unit is

One motor neuron and it’s axon and

All of the muscle fibers that it innervates.

o Each muscle fiber is only innervated by a single motor neuron.

o Each motor neuron activates many multiple muscle fibers.

o Motor units vary in size (large size = large tension)

Usually, small motor units get recruited first, and then

larger motor units are recruited.

Smaller motor units result in finer control (such as tongue

and finger muscles)

Muscles that need to produce lots of tension at once (like

biceps) have larger motor units.

o 3 Categories of Motor units

Type S (slow) motor units

Contain slow oxidative muscle fibers

They contract and relax slowly. Long term tension

These are used for maintaining posture and position.

Type FR (fast fatigue-resistant) motor units

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Contain fast oxidative muscle fibers

Fast, strong contractions

Fatigue resistant

Used for routine movements (Walking etc)

Type FF (fast fatiguing)

Contain fast glycolytic muscle fibers

Fastest, strongest contractions

Rapidly fatigue

Fibers used to rapidly generate maximum force.

o S is recruited first, then FR, and then FF

FF is rarely used on a daily basis though.

-------------------------- End Midterm 3 Material ------------------------

------------------------ Begin Final Exam Material -----------------------

Lecture 25 (5/1) (Collins) - Reproduction

Asexual Reproduction – genes come from 1 parent.

o Usually relies on mitotic cell division

o Allows animal in isolate to reproduce, and can very rapid.

o It’s also advantageous in stable, favorable environments.

Types of asexual reproduction -

o Fission – separation of parent into two or more individuals of

approximately equal size.

o Budding – New individuals splitting off from existing one.

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o Fragmentation – breaking the body into several pieces, which

will develop into complete adults (regeneration)

Animals may reproduce exclusively asexually or sexually, or they may

alternate between the two.

Parthenogenesis- A process where an egg develops without being

fertilized.

Sexual reproduction –

o Genes come from a fusion of 2 haploid cells (Called gametes) to

form a zygote that is diploid

Haploid – 1 set of DNA, diploid – 2 sets of DNA.

o Two types of gametes -

Ovum (egg/female) – usually a relatively large and

nonmotile cell

Spermatozoon (male) – usually a small motile cell.

o Advantages of sexual reproduction is genetic variability by

creating unique combinations of genes.

Hermaphroditism – each individual has both male and female

reproductive systems.

o For ex. earthworm has both

o Sequential hermaphroditism – an individual reveres its sex

during its lifetime.

Reproductive cycles –

o Most animals display cycles of reproductive activity

o It’s controlled by hormones and environmental cues.

o Generally, reproductive happens when energy is available and

environment favors offspring

External fertilization – eggs are shed by females, and fertilized by

the males, in the environment.

o Typically happens in an aquatic environment- All life is aquatic

o Usually produces a lot of offspring with little to no protection

or care.

Internal fertilization – sperm is deposited in the female, and

fertilization occurs in the mother.

o Usually produces a small number of offspring, and provide

protection.

Human Reproduction

Sexual differentiation

o Humans, have 23 pairs of chromosomes. 22 pairs of autosomes, and

1 pair of sex chromosome.

o X & Y – 1 pair of sex.

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o Males have 1 X & 1 Y chromosome. Females are 2 XX chromosomes.

o SRY gene, sex determining gene on the Y chromosome.

A functioning SRY gene will produce the SRY protein, which

will lead to the gonadal tissue to becoming a testes.

Without a SRY gene, you’ll have ovaries.

o The gonadal tissue, once differentiated, will them produce

different hormones and proteins, that will do everything else.

Around the gondal tissue, you have 2 systems of ducts – the mullerian

duct, and the wolffian duct.

o The mullerian duct forms the utures, fallopian tubes and part of

the vagina

o The wolffian duct forms the prostate, and seminal vesicles, etc.

o The SRY protein affects the medulla of the gonadal tissue and

cause differention.

o Testes will produce anti-mullerian hormones, which will prevent

the mullerian duct from growing, and the duct will degenerate.

Testes will also produce testosterone, which will develop

the wolffian duct into everything.

o Absense of testosterone will mean that the wolffian duct will

degenerate.

o Absense of anti-mullerian hormones will lead to the mullerian

duct growing.

SRY does not differentiate gender. It differentiates gonadal tissue.

o Default form is female

DHT, produced by the testes, will cause the external anatomy to

become male parts. Lack of DHT will cause female parts.

Male Reproductive Anatomy

o External reproductive organs

Scrotum – houses testes

& vas deferens.

Penis

o Internal reproductive organs

Testes

Accessory Glands

Ducts

Testes

o Leydig cells – Synthesize and

secrete Androgens

(testosterone)

o They develop high in the

abdominal cavity, and descend

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later. Lower temp outside the body favors sperm production.

o Seminiferous tubules – highly coiled tubes where sperm cells

form

They start young, and become sperm

as they reach the lumen of the

tubule.

Each main germ cell (spermatocyte)

will produce 4 sperms.

o Sperm will mature in the epididymis.

Accessory Glands

o Seminal Vesicles – 60% of volume of

semen.

Thick & Alkaline – mucus, sugars,

enzymes, prostaglandins

Sperm need to be in an alkaline

environment to thrive.

o Prostate Gland – largest accessory gland

Secretes thin milky fluid into urethra

o Bulbourethral glands –

Secretes clear mucus fluid before ejaculation

Neutralizes acidic urine.

Carries some sperm released before ejaculation.

Pathway for Sperm – SEVEn UP

o Seminiferous tubules Epididymus vas deferens ejaculatory

duct urethra Penis

Erection

o Penis is composed of three spongy cylinders of erectile tissue

o During vasodilation, leads to erectile tissue, filling with

blood.

Increasing pressure cuts off the veins that drain the penis

Female Anatomy –

o External structures –

clitoris, labia, vaginal

opening.

Clitoris gets erect

during arousal too.

o Internal structures –

ovaries and ducts.

Ovaries are enclosed in tough

connective tissues

o They aren’t attached to

fallopian tubes.

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They’re attached by ligaments to uterus

Ovaries Contains many follicles

o Each follicle contains 1 egg surrounded by layers of cells.

o Cells of the follicles produce estrogen.

o All 400,000 follicles are formed before birth

o After an egg is expelled from a follicle, the femaining tissue

forms a solid mass (Corpus luteum) that secretes estrogen and

progesterone.

o The primary cell (oocyte) form 2 forms 2 polar bodies and 1

ovum.

Pathway for Ovum

o Ovum is released into abdominal cavity near the fallopian tubes.

o The cilia on the will draw the ovum into the tube.

o Fertilization happens in the fallopian tubes.

o Ovum passes through the uterus. The endometrium (inside) of the

uterus gets very thick.

o If Ovum isn’t fertilized, the endometrium degenerates, which

produces menstrual flow.

o Then the ovum + blood flow out of the vagina.

Reproductive Hormones

o Testosterone

o 17 β-estradiol (form of estrogen)

o Progesterone

o Oxytocin

o Prolactin

Male hormonal control of reproduction

o Hypothalamus has anterior pituitary gland produce FSH & LH.

o FSH affects sertoli cells, which increase spermatogenesis

o LH affects leydig cells and have them make testosterone,

o Testosterone also stimulates spermatogenesis

o Testosterone serves as negative feedback to the brain.

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Hormonal Control of

reproduction for females

o Cyclic Behavior

o Menstrual cycle –

endometrium enlarges

and then breaks down

o Ovarian Cycle –

oogenesis leading to

ovulation

Cycle starts on Day 1

o Menstrual flow

o Low levels of

estrogen &

progesterone

o Hypothalamus causes

release of LH & FSH

o FSH starts oogenesis

of an oocyte

o This causes estrogen

synthesis by the

follicle

Estrogen increase causes

increase in the

endometrium.

o This starts shutting

the hypothalamus down

though (negative

feedback)

Very high estrogen levels

stimulates section from

hypothalamus – positive feedback.

o There’s a surge of LH.

o This causes ovulation.

o This occurs during day 14.

Corpus luteum, the ruptured follicle, starts releasing estrogen and

progesterone.

o Progesterone shuts down the hypothalamus again. (negative

feedback)

o Progesterone stimulates endometrium build up.

If ovum isn’t fertilized, the corpus luteum runs out of estrogen and

progesterone 12 days after ovulation. This leads to menstruation, and

a restart of the cycle.

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If fertilization happens, the embryo/placenta will produce HCG, which

supports the corpus luteum, and prevents the corpus luteum from

running out.

---------------------------- End BIO 203 Notes ---------------------------

Your biology skill has now increased. You must now rest and meditate on

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