Introduction to Human Physiology

What is physiology?

It is the science that deals with the function of organs and systems and the way they do this functions and the way they integrate.

Exams and marks

250 marks:125 final exam45 practical30 oral40 midterm10 shock exam

Man and the environment

External environment: (variable surroundings)The environment man lives in,

interacts with (benefits and hazards)

Major environmental factors are: oxygen, water, food, physical factors, social factors, micro organisms and parasites.

Body-Fluid CompartmentsH20:60% of TB.Wt. in adult male. 75% of TB.Wt in infants

Less than 60% in adult female and obese people

TBW is disributed as:

Intracellular compartment (ICF) Extracellular compartment (ECF)

Fluid inside the cells Fluid outside the cells

2/3 of TBW. 1/3 of TBW

40% of TB.Wt 20% of TB.Wt

2 Subdivisions:Blood plasma IVF (5%)Interstitial fluid ISF (15%)

Body water

Cell water= 40% Interstitial fluid=15%

In

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r flu

id=

5%

Capillary wall

Sto

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h& in

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lungs

Kidneys &skin

The concentration of the minerals in the intracellular fluid is different from the concentration of them in the extra cellular fluid.

The total blood volume is 8% of TBWt

Intracellular fluid Extra cellular fluid

ICF Plasma ISF CATIONS mmol/L

Na 10 145 150

K 155 4.5 4.0

Ca 0.001 2.5 1.5

Mg 13 1 1ANIONS mmol/L

Cl 3 115 110

HCO3 10 28 27

HPO3 50 1 1

Glucose 1 4-6 4-6

Proteins ratio 4 1 O-1

Osmolality Osmol/L 300 300 300

Determination of the volumes of water in the body Fick`s principle

Indicator: inert, non toxic, not utilized by tissues.Known amount of indicator is injected intravenously

9gmTime is allowed for uniform diffusionA sample is withdrawn to determine the concentration

in the plasma 3gm/L

Volume of the compartment (volume of the distribution)

= amount injected / concentration in plasma

9 gm/3gm/L= 3L

Application: 1- TBW:Heavy water (D2O) deuterium oxide

2- ECF:Inulin (polysaccharide fiber) or Na thiocyanate

(NaSCN)

3- Plasma: Evan`s blue or radioactive plasma proteins

4- ICF: TBW- ECF

5-ISF: ECF-Plasma volume

Homeostasis

The internal environment is the interstitial fluid that surrounds the cells

The internal environment

The human body consists of organs& tissues that are formed of cells.

The cell is the smallest unit of life.The cell is surrounded by interstitial

fluid (Internal Environment).The composition of the internal

environment should remain constant within narrow limits.

Internal environment

All the life processes have only one goal, that is to keep the internal environment constant, and this fixity of the internal environment is necessary condition for life

Homeostasis:It is all the physiological processes that are

carried out by all body systems.It is to insure that chemical and physical

structure of the internal environment is kept constant in spite of external (e.g.: temp, oxygen tension, pressure) or internal

(e.g.: increased muscular activity) changes.It deals with all automatic reactions which

take place to correct all deviations from normal

It is a necessary condition for the existenceFailure of homeostasis often leads to

diseases and death.

Body water

Cell water= 40% Interstitial fluid=15%

In

tra

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ula

r flu

id=

5%

Capillary wall

Sto

mac

h& in

test

ine

lungs

Kidneys &skin

Cell membrane

Exchange and communication are key conceptsfor understanding physiological homeostasis.

ICF ISF plasma organs

external environment

internal environment

Toxic Chemicals

TraumaViruses

Bacteria

CancerAutoimmune

DiseaseSickle cell anemia

Diabetes

Homeostasis: The body’s ability to maintain a stable internal environment.

Example for homeostasis

Cells consumes glucose & O2Cells takes glucose & O2 from ISF

(1st exchange through cell membrane)ISF takes these substances from

blood

(2nd exchange through capillary wall)Blood brings new nutrients & O2

from systems from external environment

CellUnit of function of living organismCells with similar properties….… tissue.Different tissues……organs.Complementary organs…..systemsThe structure of the cell varies according

to the function (specialization)No typical cellAll cells are formed of mass of

protoplasm surrounded by cell membrane

The Cell Membrane *Very thin (7.5-10 nm) *Elastic *Semipermeable

* Dynamic * EM: lipid bilayer & proteins *Made of proteins 55%, phospholipids 25%, cholesterol 13%, other lipids 4% &CHO 3%, *amphipathic (hydrophilic & hydrophobic)

Phospholipids

Fatty acid

Phosphate

Flexibility & selective permeability

Fatty acid tails– hydrophobic

Phosphate group head – hydrophilic

Arranged as a bilayer

Phospholipid bilayer

polarhydrophilicheads

nonpolarhydrophobictails

polarhydrophilicheads

Protein:

*Hydrophilic & hydrophobic

*Integral & peripheralCholesterol: permeability & toughness CHO: recognition sites & attach cells

togetherGlycoprotein Glycolipid

Peripheralprotein

Cholesterol

Functions of membrane proteins 1- structural ptns 2- passive channels: ungated & gated(voltage / ligand) 3- carriers for facilitated diffusion 4- carriers for active transport (uniport /symport/ antiport) 5- receptors: number & sensitivity change 6- enzymes 7- identity ptns 8-intercellular connections: a. binding j: tight & desmosomes

b. gap j 9- cell adhesion molecules 10- fixation of cytoskeleton

Many Functions of Membrane Proteins

Outside

Plasmamembrane

InsideTransporter Cell surface

receptorEnzymeactivity

Cell surface identity marker

Attachment to thecytoskeleton

Cell adhesion

Intercellular connectionsbinding and channel junctions

Gap junctions: for rapid propagation of electrical activityallow rapid passage of ions and molecules up to MW1000 diameter is regulated by Ca, pH, hormones and drugs

Membrane carbohydrates Play a key role in cell-cell

recognition– ability of a cell to distinguish one cell

from another• antigens

– important in organ & tissue development

– basis for rejection of foreign cells by immune system

2007-2008

Movement across the Cell Membrane

DiffusionAll molecules are in constant motion

Diffusion: Passive movement from high low concentration

Diffusion: Passive movement from high low concentration

Diffusion across cell membrane 1- simple diffusion: with concentration gradient- no energy- no carrierDiffusion rate α con gradient x surface area x temp /√mol wt x distance

1- through lipid bilayer:

Lipid soluble sub Water Lipid insoluble sub (urea)

2- through protein channels:

Ions electrically charged hydrated

Each protein channel is specific through diameter, shape, electrical charge & gates

Selective permeability gating

2- facilitated diffusion: with conc. gradient, passive, carrier for large moleculesCharacters: Specificity competition rate increases with concentration

gradient up to maximum more sensitive to temperature

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Facilitated Diffusion

Diffusion through protein channels– channels move specific molecules across

cell membrane– no energy needed

open channel = fast transport

facilitated = with help

high

low

Osmosis is diffusion of waterDiffusion of water from

high concentration of water to low concentration of water– across a

semi-permeable membrane

– The pressure necessary to stop solvent mol movements= osmotic pressure

– The numbers of particles per unit volume of fluid– Measured in mmHg– Osmole osmolarity osmolality

The osmolarity of ICF=that ECF=300 mosmol280 mosmol is due to Na, Cl & HCO320 mosmol is due to proteinTonicity: is the osmolality of a solution relative to

the plasmaPlasma proteins of blood is called oncotic

pressure. It is important for capillary circulation &regulation of ECF

Concentration of waterDirection of osmosis is determined by

comparing total solute concentrations

– Hypertonic - more solute, less water

– Hypotonic - less solute, more water

– Isotonic - equal solute, equal water

hypotonic hypertonic

water

net movement of water

Donnan effect

The protein anions inside the cells are non diffusible hinder the diffusion of diffusible cations

More osmotically active particles inside the cell

The cell tends to swellBut the Na+/ K+ pump prevents cell

rupture

Donnan effect4K+ 4K+

4Cl- 2Cl- & 2 Ptn-

3Cl- 3Cl-& 2Ptn-

3K+ 5K+

3. Gibbs-Donnan Equilibrium - YouTube.flv

Active Transport

“The Doorman”“The Doorman”

conformational change

Against concentration gradientNeeds carrier proteinEnergy is needed

ATP

low

high

symportantiport

Active transportMany models & mechanisms

ATP ATP

Active transport

1ry active:

*eg Na+/K+ pump

*α &β subunits

*α subunit contains 2 binding sites for K+ on the outside & 3 binding sites for Na+ on the inside & an ATP binding site

*β subunit has ATPase activity.

2ry active:

*eg Glucose transport 2ry to active transport of Na

1st Na pumped out ….creates concentration gradient… Na & glucose bind a carrier…transports them to inside

In active transport, energy is used to move a solute against its concentration gradient.For each molecule of ATP used, 2 K+ are pumped into the cell and 3 Na+ are pumpedout of the cell.

Outside of cell

Inside of cell

Na+

K+

Sodium–potassiumpump

Figure 5.13 Primary Active Transport: The Sodium–Potassium Pump

Getting through cell membranePassive Transport

Simple diffusion diffusion of nonpolar, hydrophobic molecules

lipids high low concentration gradient

Facilitated transport diffusion of polar, hydrophilic molecules through a protein carrier

high low concentration gradient

Active transportdiffusion against concentration gradient

low highuses a protein pump requires ATP

Vesicular transport

ATP

Transport summary

simplediffusion

facilitateddiffusion

activetransport

ATP

How about large molecules?Moving large molecules into & out of

cell– through vesicles & vacuoles– endocytosis

• phagocytosis = “cellular eating”• pinocytosis = “cellular drinking”

– exocytosis

exocytosis

Endocytosis

phagocytosis

pinocytosis

receptor-mediated endocytosis

fuse with lysosome for digestion

non-specificprocess

triggered bymolecular signal

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Exocytosis The opposite of endocytosis is exocytosis. Large molecules that are manufactured in the cell are released through the cell membrane.

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These are carrier proteins. They do not extend through the membrane. They bond and drag molecules through the bilipid layer and release them on the opposite side.

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Vesicle-mediated transport Vesicles and vacuoles that fuse with the cell membrane may be utilized to release or transport chemicals out of the cell or to allow them to enter a cell. Exocytosis is the term applied when transport is out of the cell.

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Cell Membrane - Function - Endocytosis The cell membrane can also engulf structures that are much too large to fit through the pores in the membrane proteins this process is known as endocytosis. In this process the membrane itself wraps around the particle and pinches off a vesicle inside the cell. In this

animation an ameba engulfs a food particle.

Clatherin mediated endocytosis

Endocytosis and Exocytosis

Endocytosis

Any Questions??

Quiz i. Explain the transport function of the plasma membrane protein ii. 1- Glucose transport into the intestinal cells can be increased by: a. increase temperature b. increase galactose concentration c. increase concentration gradient for glucose without limits d. increase the thickness of the cell membrane

2- Concerning the body water compartments: a. the intravascular compartment is the largest compartment b. the interstitial fluid is the internal environment c. Ca2+ is the main cation intracellularly d. protein is more in the interstitial fluid than in the plasma

3- Inulin is used for direct measuring the volume of: a. ECF b. IVF c. total body water d. plasma volume

Endocytosis and Exocytosis

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Receptor Proteins These proteins are used in intercellular communication. In this animation you can see the a hormone binding to the receptor. This causes the receptor protein release

a signal to perform some action.

Intracellular communications

A] 3 main types of communication:1- intercellular gap junctions2- neural neurotransmitters3- endocrine communication, paracrine, autocrine B] messengers bind receptorsC] intracellular effects through:1- opening channels2- activation of adenyl cyclase3- increase free intracellular Ca2+

Intercellular communications

Gap Junctions SynapticParacrine &

Autocrine Endocrine

Directly from cell to cell

Across synaptic cleft

By diffusion in interstitial fluid

By circulating body fluids

Local Local Local diffusion Systemic

Regulating systems

1- endocrine system: slow prolonged effect2- nervous system: rapid short effect

The neuronThe basic structural unit of the nervous system.Structure: The somaThe dendrites: antenna like processesThe axon: hillock, terminal buttons

Types of nerve fibersa- myelinated nerve fiber:Covered by myelin sheath

b- unmyelinated nerve fiber:Myelin sheath is absent

Synapses: it is the site where the axon of one neuron ends &

the dendrites of another beginsThere is space called synaptic cleft Chemical transmitters are released

at synapses