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How humans and other animals function
Physiology
The abnormal function seen in animal and human disease
Pathophysiology
New methods to treat pathophysiological diseases
Translational research
The property of a system that regulates its internal environment
* Either open or closed
Homeostasis
Predetermined value or range that is the "happy place" or desired point
* Relative to the person and can change over time
Set point
Change in variable being regulated causes responses that moe the variable in a direction opposite of the original change
* Ex: temperature control, regulation of glucose concentration in blood
Negative feedback
Control evaluates the changes and activates the effector to accelerate the original change
* Ex: childbirth and release of oxytocin with contractions that stimulates more contractions
Positive feedback
Uses cues (internal or external) to stimulate changes in anticipation of a change
* Ex: Pavlov's dogs, fear cues cause increase in adrenaline before threat is imminent
Feedforward regulation
ECF
* high Na+ levels; low K+ levels
* 1/3 total body water
* interstitial fluid (75-80%; fluid surrounding cells); plasma (20-25%; fluid portion of blood)
ECF: Na+/K+ levels? how much total body water? segments?
ICF
* high K+ levels; low Na+ levels
* 2/3 total body water
ICF: Na+/K+ levels? how much total body water?
1) regulate passage of substances into and out of cells
2) detect chemical messengers arriving at cell surface
3) link adjacent cells together
4) anchor cells to extracellular matrix
4 functions of cell membranes
Fat-soluble substances (O2, CO2, alcohol)
* NOT WATER-SOLUBLE SUBSTANCES bc lipid bilayer
What goes through the membrane?
1) Peripheral
- not embedded; not covalently bound; easily broken away by mild treatments
2) Integral
- embedded/anchored in membrane
a) transmembrane (span bilayer 1 or more times; touches ECF and ICF)
b) non-transmembrane (embedded but does not span... doesn't touch both ECF and ICF)
Types of proteins in cell membrane
1) Desmosomes (rope-like attachments between cells - strength and connection)
2) Tight junctions (cell membranes of 2 cells fuse together - transcellular across epithelium)
3) Gap junctions (hollow tubes between each cell)
Membrane junctions
Endo - cell taking things in
Exo - cell getting things out - 1) replaces old portions of plasma membrane and 2) gets out membrane-impermeable molecules
Endo/exocytosis
1) Pinocytosis (cell drinking - non-specific)
2) Phagocytosis (cell eating)
3) Receptor-mediated (bringing in a receptor - specific)
Types of endocytosis
Simple diffusion only
What type of transport is not carrier-mediated?
Concentration gradient
What is the driving force of the movement of molecules in diffusion?
1) Diffusion coefficient (how easily something will move across a membrane - relative to molecule; inversely related to molecular radius of solute and viscosity of medium aka bigger molecules move slower, and molecules move slower in a more viscous medium)
2) Membrane properties (thickness, surface area, permeability)
3) Electrochemical gradient (due to charge of ion)
What factors affect the speed of diffusion?
Na+: 140
Cl-: 100
K+: 4
Ca++: 10
HCO3-: 24
Glucose: 70-100
Protein: 0.2
ECF: 290
Extracellular solute concentrations
Bilayer: O2, CO2, fatty acids, alcohols (non-polar)
Protein channels: Na+, K+, Ca++ (ions)
What moves through the lipid bilayer? Through protein channels?
- carrier protein
- conformational change
What does facilitated diffusion require?
1) Saturation (how many solutes in solvent; limited binding sites; rate of transport increases when less solutes present)
2) Stereospecificity (binding sites for solute on transport proteins are stereospecific)
3) Competition (D-galactose and D-glucose both recognized by transport protein; must compete for finite number of receptors; one will inhibit the transport of the other)
What 3 things play a role in carrier-mediated transport (for facilitated diffusion, primary/secondary AT)?
Primary directly uses ATP to move molecules, while secondary indirectly uses ATP to move them
Difference between primary and secondary AT?
1) Na+K+ ATPase pump (3Na+ out, 2K+ in; pump maintains concentration gradient; found everywhere)
2) Ca++ ATPase pump (found in endoplasmic and sarcoplasmic reticulums)
3) H-K+ ATPase pump (found in stomach and kidneys)
Main examples of primary AT?
Inactivation gate always trancedes over the activation gate
Gated channels
*Na+ moves down its gradient, while another solute moves against its gradient --> the Na+ movement gives energy to the other solute to move
1) Cotransport/symport (molecules move in same direction)
2) Countertransport/antiport (molecules move in different directions)
Secondary AT types
Flow of water between two solutions separated by a semipermeable membrane caused by a difference in solute concentration
* aka net diffusion of water across a membrane
Osmosis
Difference in osmotic pressure between two solutions
What drives osmosis?
1) Osmolarity
2) Osmotic pressure
What is osmosis dependent on?
Concentration of osmotically active particles in a solution
* mOsm/l = gC
* g = number of particles/mol in solution
* C = concentration (mmol/L)
Osmolarity
Isosmotic: solutions have the same osmolarity
Hyperosmotic: one solution has a higher osmolarity than other
Hypoosmotic: one solution has a smaller osmolarity than other
* ECF has osmolarity of 285-300 mOsm/L
iso/hyper/hypoosmotic
Describes the ease of which a solute crosses a membrane
σ = 1 --> major water movement; solutes do not go across membrane
σ = 0 --> no water movement; solutes do go across membrane freely
Reflection coefficient (sigma)
- Amount of pressure that needs to be applied to a solution to prevent the inward flow of water through a semipermeable membrane
- Pressure exerted by the movement of solvent molecules through a semipermeable membrane lower to higher solute concentration
Osmotic pressure
Higher
* Bc more particles moving and bumping into each other
____________ concentrations of solute increase osmotic pressure.
Measure of the osmotic pressure gradient between two solutions separated by a semipermeable membrane
Tonicity
Isotonic: same effective osmotic pressures (no osmosis)
Hypertonic: higher effective osmotic pressures than other solns
Hypotonic: lower effective osmotic pressures than other solns
* Water will move from hypotonic solutions to hypertonic solutions
Iso/hyper/hypotonic
Yes!
* Can have the same osmolarity but different tonicities
Can two solutions be isosmotic but not isotonic?
Hyperosmotic; hypertonic
* Results from
1) decreased water intake
2) water loss without proportionate solute loss
3) increased solute intake without proportionate water intake
4) excess accumulation of solutes
5) loss of excessive sweat
6) hyperosmotic volume contraction
Pathophys
* Dehydration: loss of water without loss of solutes
Isosmotic
* Caused by
1) hemorrhage (bc of loss of blood volume)
2) loss of GI tract secretions (vomiting, diarrhea, ileostomy, etc)
* May lead to dehydration and hypovolemic shock
Pathophys
* Dehydration: loss of water and solutes
Hypotonic; hypoosmotic
* Caused by
1) accumulation of solute-free fluid
2) excess antidiuretic hormone (ADH) or intake of large amounts of tap water without balance oslute ingestion (elderly; marathon runner)
3) symptoms largely neurologic bc water shift to brain tissues and dilutes sodium in vascular space
Pathophys
* Fluid excess: excess extracellular water in relationship to solutes
1) Thirst
2) Weight loss
3) Dryness of mouth, throat, face
4) Absence of sweat
5) Increased body temperature
6) Low urine output
7) Postural hypotension (BP bottoms out upon standing)
8) Dizziness and confusion
9) Increased hematocrit
Clinical signs/symptoms of fluid deficit / dehydration
1) Decreased mental alertness
2) Sleepiness
3) Poor motor coordination
4) Confusion
5) Convulsions
6) Sudden weight gain
7) Hyperventilation
8) Signs of increased ICP
9) Mild peripheral edema
10) Low serum sodium
11) Low hematocrit
Clinical signs/symptoms of fluid excess / water intoxication
Isotonic volume excess
* Causes
1) vein obstructions
2) decreased cardiac output
3) endocrine imbalances
4) loss of serum proteins (burns, liver disease, allergic reactions)
Pathophys
* Fluid excess: excess of both solutes and water
1) Weight gain
2) Excess fluid
3) Dependent or pitting edema
4) Increased BP
5) Neck vein enlargement
6) Effusions
7) CHF
8) Signs of increased ICP
9) Low serum sodium
10) Low hematocrit
Clinical signs and symptoms of fluid excess / edema
Diuretics... inhibit Na+ and water reabsorption by kidneys
- K+ also usually lose too quickly --> s/s of K+ loss are muscle weakness, fatigue, cardiac arrhythmias, abdominal distention, nausea/vomiting
How is edema treated?
Measures fractional volume occupied by RBCs
Hematocrit (Hct)
Decreases
If ECF volume increases, Hct _________
Increases
If ECF volume decreases, Hct _________
Hct may be unchanged because water shifts outside of the blood vessel
Hyposmotic expansion (excessive water intake) SHOULD decrease Hct due to dilution of RBC concentration... why may it not?