fundamentals of physiology

what is physiology used to understand

● how a healthy body works

● how to maintain health (and age well/ trying to maintain quality of life as well as expand lifespan - especially important due to ageing population)

● how living organisms cope with or adapt to different

environments e.g. temperatures, altitudes

● what goes wrong in disease (pathophysiological

conditions)

● how to treat diseases

what is the The internal environment

fluid environment around cells

why must the internal environment be maintained

● Cells need a carefully regulated

fluid environment to function.

● The internal environment must

remain stable despite changes in

the external environment.

● The relatively constant steady

state of our internal environment

is achieved by homeostasis.

homeostasis

homeostasis as an active process that keeps the body in its steady state.

homeostasis vs equilibrium

homeostasis is a steady state and not an equilibrium. 

when something's in equilibrium, it's kept in balance with no energy being applied, whereas we're in a steady state, which means we're keeping everything in our bodies in balance, maintaining the appropriate internal environment, but it's costing us energy to do so. 

examples of external environment

• the space in the alveoli 

• lumen of gastrointestinal tract

examples of internal environment

• cardiovascular system

• epithelial lining of the lungs

• epithelial lining of the GI tract

• lots more

what is the internal environment divided into

extracellular fluid, which is every fluid that's outside of a cell, and we have our intracellular fluid, which is inside of the cell,

extracellular fluid, can divide into three further fluids

• blood plasma 

• interstitial fluid (IF) - anything surrounding cells

• transcellular fluid (don't need to know)

what are Vital parameters

these are the things that if they get too much out of balance, they will cause imbalance in your body and cause you to kind of move into a state of dysfunction or unhealthiness. 

what is in the blood plasma (ECF)

• Oxygen

• Glucose

• Ions e.g. Ca2+, K+, Na+, H+ (pH)

what does blood plasma regulate

• volume

• Osmolality

what is in Interstitial fluid (ECF)

• Glucose

• Ions e.g. Ca2+, K+, Na+, H+ (pH)

what does interstitial fluid regulate

Osmolality

what is in Intracellular fluid (ICF)

● ATP

● Glucose

● Ions e.g. Ca2+, K+, Na+, H+ (pH)

what does Intracellular fluid (ICF) regulate

● Volume

● Osmolality

what must be regulated in terms of the whole body

• Arterial blood pressure

• core temperature

what maintains the steady state of vital parameters

homeostasis

4 essential components of the negative feedback loop

Steady state disrupted

1. Receptors - Sense the vital parameter (input)

2. Control centre - Compares input against a set point

4. Effector - Enables a change to return vital parameter

3. Output signal - Signal from control centre to effector

where are receptors in the negative feedback loop normally found

usually found in the brain:

• hypothalamus 

• medulla 

• pons

output signals in the negative feedback loop

• nervous signal

• secretion via the endocrine system

features of Thermoregulation: a negative feedback loop

● Physiological adjustment in the opposite direction

● Returns parameters back to their original level/value

● Redundancy - multiple mechanisms present for many vital parameters

order of body fluid compartments size in the internal environment

• Intracellular fluid 25L

• Interstitial fluid 13L

• blood plasma 3L

• Transcellular fluid 1L

osmolarity

the amount of water particles

Osmolality

Total concentration of all particles that are free in a solution

mOsm

milliosmoles per kg of water

is Na⁺ conc higher in ECF or ICF

ECF

is K⁺ conc higher in ECF or ICF

ICF

is Cl^- conc higher in ECF or ICF

ECF

is Ca²⁺ conc higher in ECF or ICF

ECF but very small amounts in both

do have quite a lot of intracellular calcium, but not in the intracellular fluid

what separates blood plasma and IF

Capillary endothelium

what separates IF and ICF

cell (plasma) membrane

what is the phospholipid bilayer impermeable to

○ large molecules e.g. proteins,

nucleic acids

○ charged, water soluble

substances e.g. ions

what is the phospholipid bilayer permeable to

● hydrophobic molecules e.g. O2, CO2, steroid hormones

what is the phospholipid bilayer partially permeable to

uncharged polar molecules

what are steroid hormones derived from

derived from cholesterol, so they can move through a membrane quite easily

functions of the cell membrane

the phospholipid bilayer and specific membrane proteins:

● maintain homeostasis

● allows the movement of specific substances

● results in the development of a membrane potential

● allows the development of action potentials

tissues definition

group of similar cells and products arising from same embryonic region, working together to perform a specific physiological or structural role

what are the Four broad classifications of tissues

● Epithelial tissue - protective/barrier

● Muscle tissue - movement/heat generation

● Nervous tissue - communication/coordination

● Connective tissue - structural support/connecting

how do the Four broad classifications of tissues differ

in types + functions of cells; characteristics of the ECM; space occupied by cells/ECM, eg. muscles and epithelia ECM is scarce - much more prevalent in connective tissue

what is Epithelial Tissue

Epithelial Tissue

features of Epithelial Tissue

● First line of protection/defense - physical (stratified), chemical, biological

● Control permeability - selective physical barrier

● Secretes - mucus/enzymes onto external/internal surface, hormones into

blood, ions, acid/alkali

● Absorbs - water, macromolecules, ions

● Diffuses - gases through capillaries: tissues and lungs (squamous)

epithelia tissue common properties

● Highly cellular - tightly packed continuous cell layer → sheets

● Polarised - distinct apical + basolateral domains determine function

● Basement membrane (even simple squamous)

● Avascular + innervated - no blood vessels running through but do have nerves

● Regenerative

● Intercellular adhesion - connected by tight junctions → properties

what are the 3 types of muscle tissue

● Skeletal: Voluntary movement - bone + soft tissues e.g. tongue/

upper oesophagus, eyes, diaphragm, face, sphincters anus/urethra

● Cardiac: Heart only not vessels, contracts involuntarily to pump blood

● Smooth: Organ walls (e.g. GI tract) to move substances, involuntary

shared properties of muscle tissues

Myocytes; excitability; contractility; extensibility

skeletal muscle tissue properties

long bundles striated multinucleated fibres (cells fused in development) surrounded by connective tissue

cardiac muscle tissue properties

highly branched, striated, 1-2 nuclei, intercalated discs + gap junctions→ functional syncytium

smooth muscle tissue properties

no striations, overlapping sheets spindle-shaped cells, single nucleus, gap junctions, dense bodies

functions of neurones

carry electrical signals (action potentials) to each other to control + coordinate bodily function in CNS,PNS + ENS

structure of nerve cells

● Cell body - cellular functions

● Dendrites - cytoplasmic processes carry

impulses to cell body

● Axon - carries impulses from cell body, forms

synaptic connections

how many types of cells in nervous tissue

two

what is the ENS

the enteric nervous system. A separate nervous system, although it's in the periphery that sits within the gastrointestinal tract. 

the GI tract is such a large organ system and requires such a lot of control and coordination so has its own immune system 

role of Neuroglia (glial cells)

Support, protect, insulate, provide nutrition to neurones

depending on where you are, whether you are in central nervous system or the peripheral nervous system, some of the supporting cells will be given different names. PNS - Schwann cells, CNS - might have oligodendrocytes.

role of Nervous Tissue ECM

ECM supports cells - soft, porous dynamic + biologically active tissue network. Helps direct brain development, maturation + aging, synaptic function.

ECM remodeling heavily linked to brain aging + disease pathology

e.g. neurodegeneration, cancer, epilepsy

components of the nervous tissue ECM

● Hyaluronic acid (HA)

● Proteoglycans 

● Interstitial matrix

● Perineuronal nets

CNS ECM - 10-20% total brain volume:

Microglia (Brain Scouts) function

brain's resident immune cells, constantly moving their branches to "survey" the dense, interconnected web of neurones and astrocytes

Enteric glia present in ENS

examples of connective tissue

● Specialised cells in CT defend body from microorganisms that enter

● Transport of fluid, nutrients, waste, chemical messengers by blood/lymph - specialised fluid CT

● Sheath surrounding muscle cells

● Tendons attach muscles - bones

● Skeleton

● Fibrous capsules/bones around organs

● Triple layer in brain meninges

● Adipose cells store surplus energy (fat) and thermally insulate the body.

role of connective tissue

Performs many functions in the body, supporting/connecting other tissues

how is the connective tissue formed

Derived from embryonic mesodermal layer→mesenchyme: highly varied, static → dynamic

Three main structural components of connective tissue

1. Specialised cells: (fibroblasts, adipocytes, macrophages, mast cells

and leukocytes)

2. Protein fibres:

○ Collagen: tensile strength - resists pulling forces (± reticular)

○ Elastic: flexibility + recoil

3. Ground substance (Interfibrillar matrix):

○ Fluid - transport/communication e.g. blood

○ Gelatinous - support/shock absorption e.g. cartilage

○ Calcified - rigid support/protection e.g. bone

what are reticular forces fibres

a specialist type of collagen fibre. 

classification of connective tissue

connective tissue → proper + specialist

proper → loose (areolar) + dense (regular, irregular, elastic)

specialist → (adipose, cartilage, bone) + (blood, lymph)

functions and features of CT proper - loose

Holds organs, structures, tissues in place:

❖ beneath epithelia

❖ surrounds blood vessels/nerves/oesophagus/trachea

❖ cell ‘mesh’ lymph nodes/spleen/bone marrow/liver

❖ fascia between muscles (lubricating HA between)

❖ mesenteries, visceral pericardium, lung pleura, meninges(2)

● Highly vascular (esp. skin)

● Variable spaces between fibres, more compact under skin

● Cells < gelatinous ECM. Collagen + elastic fibres embedded

(± reticular), permitting ECF diffusion

● Fibroblasts > adipocytes, macrophages, mast cells, leukocytes

functions and features of CT proper - dense

High tensile strength, densely packed collagen > ground substance + cells

Arrangements:

● Regular (parallel fibres of tendons/ligaments: strength/shock absorption)

● Irregular (multidirectional fibres e.g. dermis)

● Elastic (embedded elastin/fibrin e.g. arteries: concentric rings)

examples of Connective tissue migrating cells

Interstitial leukocytes - ‘immuno-wanderers’:

○ Dendritic cells - peripheral tissues → lymph nodes

○ Plasma cells - loose connective tissue < lymphoid tissue → antibodies

○ Monocytes - when stimulated → macrophages

○ Macrophages - organ specific, e.g. move over alveolar surface → phagocytosis

○ Eosinphils - WBC/leukocyte migrate through capillary walls to connective tissue

○ Mast cells - connective tissue (NB skin/gut) → release histamine

types of Specialised CT - Solid

adipose tissue - White/brown/beige/pink - determined by organelles

Lipid storage, secretory, insulating, shock absorbing

cartilage -

types of Specialised CT - Fluid

blood - Connects all bodily systems, RBC, WBC, platelets. Nutrients, salts, waste dissolved in ground substance

lymph - Collects from interstitial fluid, returns to blood to maintain fluid levels, immune response - liquid matrix + WBC

function and developmental origin of epithelia

- barriers to separate compartments

● Functional interface between two environments, e.g.:

     ○ Skin separates the body from the  external environment

    ○ External environment ‘enters’ the body via respiratory system and GI tract

● Most abundant and functionally diverse tissue - all organs

● Develops from all germ layers

examples of function of epithelia

dynamic barriers that cover surfaces, line cavities and form glands:

Protection - skin

Selective barrier - BBB

Contractile - myoepithelia

Diffusion/waste - lung

Absorption - SI

Secretion - glands

Filtration - podocytes

Lubrication/propulsion - trachea

Epithelia - common properties

● Highly cellular - tightly packed continuous cell layer → sheets

● Polarised - distinct apical + basolateral domains

● Basement membrane

● Avascular + innervated

● Regenerative

● Intercellular adhesion - connected by tight junctions → properties

● Tissue specific specialisations:

○ Isoforms of laminin/collagen IV

○ Proteoglycan + accessory protein variation

○ Assembly/arrangement

● Upper BL secreted by epithelial cells

○ Collagen IV - main structural component

○ Laminin - ‘molecular glue’

● Lower RL from connective tissue fibroblasts

(collagen III + VII )

how does the basement membrane of epithelia prevent cancer

many cancers formed from epithelia cells, basement membrane stops them metastasizing and moving elsewhere in the body.

basement membrane composition

A mesh of interconnected fibres

● Physical foundation - anchors + separates

epithelial tissue from connective tissue

● Selective filter supplying nutrients, oxygen +

removing waste

● Guides epithelial cell migration during wound

healing

● Prevents carcinomas accessing lymph

what drives passive transport? 

electrochemical gradients

● Always depends on the concentration gradient of the solute

● For charged molecules also depends on any difference in voltage between the ECF and ICF (e.g. Cl- and Na+)

what is the Electrochemical gradient

the sum of the 2 forces:

• concentration gradient

• difference in voltage between the ECF and ICF

what is simple diffusion

Movement of an uncharged, hydrophobic solute (e.g. CO2) through the lipid bilayer

what does Jx = Px ([X]o - [X]i) calculate

● How fast the solute X moves can be described by its flux (Jx).

● Flux (Jx) depends on:

○ Permeability coefficient of X (Px), how easily X can move through the membrane (NB for drug design)

○ Difference in [X] between ECF and ICF (concentration gradient)

what are transmembrane proteins classed as

● integral membrane proteins

● Composed of membrane-spanning ɑ- helical domains

● Can be single pass or multi pass

● How proteins move in and out of the membrane define a protein’s membrane topology

how do hydrophilic solutes pass through the membranes

transmembrane proteins

what are the types of transmembrane proteins

• pore (non-gated channel)

• channel (gated pore)

• carrier

• pump

All have multiple transmembrane segments surrounding a solute permeation pathway

what regulates hydrophilic solutes transport rates

Membrane transport proteins and concentration

how do solutes pass through membrane transport proteins

Solutes pass through the membrane without contact with the hydrophobic membrane core (permeation pathways)

● Amphipathic helices

○ alternating hydrophobic and hydrophilic amino acids

● Hydrophobic surfaces face the lipid membrane

● Hydrophilic surfaces create a central pore

how do Pores allow facilitated diffusion

● Driving force for movement is the electrochemical gradient

● Always open

● Multiple subunits

● Example, aquaporins (AQP)

what is a non gated channel

a constantly open channel that allows the transmission of solutes from one side of the membrane, in this case the extracellular space, into the intracellular space. 

how do Channels allow facilitated diffusion

● Driving force for movement is the electrochemical gradient

● Gated ion channels

● Multiple subunits

● Example, potassium channel

important in neurones

what do all channels have

1. a moveable gate

2. a sensor:

○ voltage

○ ligand

○ mechanical

3. a selectivity filter

4. an open channel pore

types of channels

• voltage gated

• extracellular ligand

• intracellular ligand

• mechanical-gated

how do Carriers allow facilitated diffusion

● Driving force for movement is the electrochemical gradient

● Never has a continuous transmembrane path

● Example, GLUT (glucose transporters)

what is Flux (Jx) limited by

○ Number of carriers in the membrane

○ Speed by which the carrier can cycle through the steps

• Jmax = [X] is high enough to occupy all of the carriers

how can Carriers can mediate active transport

● Achieved through the use of:

○ Pumps

○ Cotransporters

○ Exchangers

what are the Two types of active transport

1. Primary active transport uses pumps

● Driving force = a chemical reaction e.g. ATP hydrolysis

2. Secondary active transport uses cotransporters and exchangers

● Driving force = coupling the downhill movement of one solute with the uphill movement of another solute.

how do Cotransporters move both solutes

• in the same direction

● Requires a ‘driving’ solute whose electrochemical gradient provides the energy

○ Often the inward Na+ electrochemical gradient

● Example, Na+/glucose cotransporter

*also called symporters

how do Exchangers move solutes

• in opposite directions

● Requires a ‘driving’ solute whose electrochemical gradient provides the energy

○ Often the inward Na+ electrochemical gradient

● Example, Na+/Ca2+ exchanger

*also called antiporters

what are the Two routes across an epithelial sheet

● Transcellular - crossing AM and BLM membranes (passing through cytoplasm)

● Paracellular - moving between cells through tight junctions (NB variation ‘leakiness’)

what does a Transepithelial voltage indicate

electrical resistance and permeability of TJs

if we put an electrode in the lumen and inside the cell, we can effectively measure the electrical resistance of the apical membrane. 

And then we could do exactly the same on basilitral membrane. 

 the transepithelial resistance will be the sum of the two. 

what is the  the transepithelial resistance  

the sum of the voltage between the lumen and cell and the international space and cell

whats the purpose of leaky epithelia

‘Leaky’ epithelial perform bulk transepithelial transport of solutes and

H2O in isosmotic conditions, e.g. :

● Small intestine (SI)

● Kidney proximal tubule (PT)

bulk transepithelial transport of solutes and therefore water, because water will eventually follow in isosmotic conditions. 

whats the purpose of tight epithelia

‘Tight’ epithelia generate/maintain large transepithelial ion concentration or osmotic gradients, eg. urinary bladder

when does water move passively across an epithelium

H2O moves passively across an epithelium in response to osmotic gradients

Eg. an epithelium secreting salt will secrete fluid and vice versa

● Small water molecules can cross the apical and basolateral membranes, but aquaporins (AQP) ↑↑ H2O permeability: ↑↓ hydraulic conductivity

● Bilayer H2O permeability ensures osmotic equilibration is rapid, however membrane composition + [AQP] regulated