PHGY 209 - Midterm

body fluids, transport mechanisms, blood, immunology

physiology

the study of normal functional activities in healthy living organisms

homeostasis

state of dynamic constancy

fundamental principle of physiology

at all levels of organization the functional activities are directed at maintaining optimal and relatively constant internal conditions

Milieu Interieur

“internal environment”

1. environment surrounding individual cells is vastly different from outside environment

2. internal conditions remain relatively constant under conditions of health

aspects of body fluids

volume, distribution, characteristics, functions

average amount of water in bodies

45% to 75%

what is body water the medium for

1. solutes dissolving

2. where metabolic reactions occur

what are functions of body water

1. regulating body temp

2. moistening tissues

3. lubricating joints

4. protecting organs/tissue

5. preventing constipation

6. helps liver and kidney by removing waste

7. dissolve minerals so body can use them

8. carries O2 to cells

what causes difference in the amount of water in individuals

adipose tissue

% of water in various tissue

skin = 70%

muscle = 75%

heart, liver, brain, kidney = 70-80%

bone = 25%

fat = 10%

what happens to % of body water as fat increases

as fat increases water decreases

factors that affect body water

age, sex, weight

standard body water for male, white, 70 kg, 21

60%

variations in body water due to age and sex

infant = ~75% - little fat

18-40 = ~50% (female) - estrogen = deposition of fat in breasts ~60% (male)

elderly = ~45% (female) ~50% (male) - decrease in muscle tissue which is replaced by connective tissue which is drier and increase in adipose tissue

MAJOR TREND = same bw for men and women until puberty when women have less bw and then trend stays the same with ~10% bw for women until death

how to calculate body water in L

weight x bw% / 100 = volume (L)

why is it important to know body water percentage

dosing for water-soluble medication

dosage = 10mg/7kg

is body water a dynamic steady state

yes bc body water remains constant in health

does water input and output have to be the same

yes

obligatory losses

required losses (~1.5 L a day)

insensible - lungs and skin

sensible - urine and stool

facultative losses

vary with intake (necessary to maintain balance)

urine (*kidney)

what kind of loss is sweat

neither facultative or obligatory b/c if you drink more water you wont sweat more

insensible perspiration vs sweating

insensible perspiration:

1. water

2. passive evaporation (affected by temp/humidity)

3. entire skin surface

4. continuous and obligatory

sweating:

1. electrolyte

2. active secretion (energy dependent)

3. sweat glands

4. activated by heavy work/temp

water turn over in adult vs baby

adult = 3-4% of body weight in 24 hours

baby = 10% of body weight

why is babies water turnover so high

1. kidneys less developed

2. no water drank to maintain electrolyte balance

3. more loss bc of high surface area to volume ratio

what does body water volume help regulate

1. normal solute concentrations

2. normal blood volume and pressure

negative water balance

1. reduced intake

2. excessive loss from gut

3. excessive sweating

4. loss in expired air (dry air at high altitudes)

5. loss in urine

water intoxication

1. excessive intake - causes cells to swell

2. renal system failure

are body water compartments and sub compartments rigidly isolated

no, water can exchange freely between them

two major body water compartments

1. intracellular fluid 2/3 - inside cells bound by cell membrane - 28 L

2. extracellular fluid 1/3 - surrounds cells - 14 L

total body water = 42 L

ECF divided into…

2 major = plasma 5% and interstitial fluid 15%

2 minor = lymph 1-2% and transcellular fluid

plasma

fluid medium in which blood cells are suspended

different parts of blood

plasma, buffy layer (WBC, platelets), red blood cells (RBC, erythrocytes)

hematocrit

percentage of blood volume that is occupied by RBC

normal value is 45%

interstitial fluid

fluid that percolates between individual cells (through capillaries and cells)

lymph

• one way finger like projections

• converge to form larger vessels which converge to form lymphatic ducts

• drain into large veins in chest

transcellular fluid

• aggregate of small fluid volumes secreted by specific epithelial cells that line body cavities

• do not contribute overall to water exchanges

percentages and groups of total water

ICF = 40%

ECF = 20%

• ISF = 15%

• plasma = 5%

methods to determine compartment volumes

1. direct (mathematically measure volume)

2. indicator dilution method

indicator dilution method

1. know total quantity of test substance introduced (through vein)

2. allow time to equilibrate

3. remove volume of blood and centrifuge to obtain plasma

4. concentration of plasma and volume of fluid after dispersion

5. use V = Q/C

factors of indicator

• non toxic

• diffuse readily and evenly

• induce no changes in distribution of water between compartments

• easy to measure its concentration

• radioactive

ECF compartment measurement

needs to cross capillary wall not cell membrane ~14 L

plasma volume measurements

cannot cross capillary wall ~3.5L

ICF of ISF volume measurements

total body water - ECF = ICF

what element is ICF high in

K+ (and Mg++) low in Na+ and Cl-

what element is ECF high in

Na+ and Cl- and low in K+

good for IV drips

physiological saline measurements

0.9% NaCl

barriers to transport between ICF and external environment

1. cell membrane - barrier between ICF and ECF

2. capillary wall - barrier between ECF and plasma, and between plasma and the external environment

permeability of cell membrane

highly permeable to: H2O, Lipid-soluble substances, Dissolved Gases (O2, CO2), Small uncharged molecules

Less Permeable to: Larger molecules, Charged particles

Impermeable to : Very Large molecules

what makes up the cell membrane

1. phospholipids - hydrophilic heads and hydrophobic tails

2. cholesterol

3. proteins - integral and peripheral

4. glycocalyx

cholesterol in cell membrane

• buffer to prevent low temps from inhibiting fluidity and high temps from increasing fluidity

• formation of vesicles that pinch off cell membrane

• lipid rafts (signalling)

proteins in cell membrane

integral - cross the membrane, close to phospholipids

peripheral - sides of plasma membrane

glycocalyx in cell membrane

formed from glycans, glycoproteins, glycolipids

• cell-cell recognition, communication, adhesion, protection

fluid mosaic model

• dynamic, fluid structure

• phospholipid bilayer = solvent for embedded proteins creating mosaic of molecules that move laterally

selective transport - proteins

channels and transporters

enzyme - proteins

amino acid transport, Na-K pump

cell surface receptor - proteins

G - protein receptor, insulin receptor

cell surface identity marker - proteins

CD4 T Lymphocytes

CD45 Leucocytes

CD68 Monocytes

cell adhesion - proteins

CAMS, cadherins, integrins

attachment to cytoskeleton

actin. microtubules, septins

two transmembrane pathways

1. phospholipid bilayer

2. interaction with transmembrane protein

passive transport types

1. diffusion

2. facilitated diffusion

3. osmosis

active transport types

1. active: primary and secondary

2. pino/phagocytosis

diffusion

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

flux

amount of solute crossing surface area per unit time

one way flux

unidirectional rate of movement of solute

net flux

overall rate of movement of solute

what is diffusion driven by

concentration gradient

when is net flux zero

at equilibrium

intracellular and extracellular concentration both starting at zero

time 0 = concentration zero for both when molecule is added to extracellular solution (Co). Co remains constant because the number of molecules required to increase Ci is small bc the intracellular cell volume is small relative to the extracellular volume.

why can diffusion only occur over small distances

Diffusion time increases in proportion to the square of the distance travelled by the solute molecules

diffusion across lipid bilayer

• Non-polar molecules and gases

• Mass of the molecule

• Concentration gradient

• Lipid Solubility

diffusion through ion channels

• concentration gradient

• electrical gradient

• ion species (Na, K, Ca, Cl)

ion channels

transmembrane proteins that show ion selectivity

what determines the movement through ion channels

opposing electrochemical forces

• electrical potential difference across membrane

• concentration gradient of that ion across membrane

ion channel gating types

1. ligand - open when molecule binds to it

2. voltage - change in membrane potential

3. mechanical - stretch or pressure

what does current flow through ion channel depend on

1. channel conductance

2. channel open time

3. frequency of channel opening

4. concentration gradient

5. membrane potential

mediated transport

movement of ions and other larger molecules by integral membrane proteins called transporters, carrriers, exchangers (slower than ion channels)

• facilitated, active transport

factors that determine mediated transport

1. solute concentration

2. affinity of transporter for solute

3. number of transporters

4. rate of transporter conformational change

characteristics of mediated transport

a. specificity - transporter likes one molecule

b. saturation - rate reaches max when all binding sites on all transporters are occupied

c. competition - similar structured molecules compete for same binding site

facilitated diffusion

presence of transporter or carrier which enables solute to move better than simple diffusion

1. solute binds to transporter

2. conformational change

3. solute on other side of membrane

4. conformation change to og conformation

NO ENERGY and HIGH TO LOW CONCENTRATION

active transport

1. transporter mediated

2. supply of chemical energy (hydrolysis of ATP)

3. susceptible to metabolic inhibitors

4. against concentration gradient

primary active transport

hydrolysis of ATP by transporter

phosphorylation of transporter changes the conformation of the transported and solute binding affinity

sodium potassium pump

2 potassium in, 3 sodium out

phosphorylation to bring Na in and dephosphorylation to bring K out

Ca - ATPase

maintain low intracellular Ca levels

H - ATPase

maintain low lysosomal pH

H/K - ATPase

acidification of stomach

secondary active transport

movement of Na down concentration gradient is coupled with transport of another solute molecule against concentration gradient - uses energy stored in the electrochemical gradient which comes from primary

sodium transporter

1. high concentration of sodium outside cell

2. Na binds to transported allowing glucose/aa to bind to same carrier

3. conformational change delivers Na and substance inside cell

4. reverts back and Na is pushed outside cell by Na/K - ATPase

secondary active transport mechanisms

symport/cotransport = solute transported in same direction as Na

antiport/countertransport/exchange = opposite direction as Na

examples of symport

Na+ with HCO3/aa/glucose cotransporters

examples of antiport

Na+ with H+/Ca++ exchangers

summary of transport mechanisms

endocytosis

cell membrane invaginates and pinches off to form vesicle

exocytosis

an intracellular vesicle fuses with the cell membrane and its contents are released into ECF

types of exocytosis

constitutive - non regulated

• replaces plasma membrane

• deliver proteins to cell membrane

• secrete collagen/other materials

regulated

• triggered by extracellular signals, increase of cytosolic Ca++

• secretion of hormones, digestive enzymes, neurotransmitters

types of endocytosis

pinocytosis

• engulfs extracellular fluid including solutes present

• non specific

• when in cytoplasm fuse with other vesicles like endosomes and lysosomes

phagocytosis

• specific and triggered

• extensions of cell membrane called pseudopodia fuse to form large vesicles that pinch off the membrane

• sometimes fuse with lysosomes where contents are degraded

• defends against infection

receptor-mediated endocytosis

molecules in ECF bind with high affinity to specific protein receptors on the plasma membrane

clathrin dependent receptor mediated endocytosis

1. ligand binds to receptor → conformational change and clathrin is recruited to plasma membrane

2. adaptor proteins link with ligand-receptor to the clathrin

3. forms cage like structure which invaginates leading to clathrin coated vesicle

4. sheds clathrin coat and fuses with endosome and lysosome

5. or fuse with membrane on other side of cell

6. clathrin and receptors recycled

LDL (low density lipoproteins)

cholesterol is transported in the blood as lipid protein particles known as LDL

differences between LDL and endocytized vesicles

endo - fuse with early endosomes where LDL dissociates from receptor protein

LDL - continues to late endosome andlysosome where cholesterol is released