W1 - Cellular physiology (1.1) Flashcards
What percentage of the total body weight is water in an adult?
Classify + values.
60% ∽42l
- 2/3, hence 40% intracellular fluid (ICF) ∽ 25l
- 1/3, hence 20% extracellular fluid (ECF) ∽ 17l
- 3/4 of ECF, hence 15% interstitial fluid ∽13l
- 1/4 of ECF, hence 5% plasma ∽ 3l
- transcellular fluid ∽ 1l
REMEMBER: 60-40-20 rule for water-ECF-ICF
What is the total blood volume of the body?
Constituents.
∽ 5l (water)
- ∽ 3l plasma (ECF)
- ∽ 2l in cells (ICF)
→ seperated by capillary blood cell membrane
What is measured for a complete blood count?
Values.
- RBC count = 4.1 - 6.1 *10^6 cells/μl
- WBC count = 4,000 - 11,000 cells/μl
- thrombocyte count = 150,000 - 400,000 cells/μl
- Hb:
- men: 160 - 170g/l
- women: 135 - 145g/l
Which fraction is described by the hematocrit?
Values.
volume percentage of red blood cells in blood
- men: 40 - 52% (∽ 45%)
- women: 37 - 48% (∽ 40%)
What are the percentages of different WBC types?
- lymphocytes = 25 - 30%
- monocytes = 4 - 8%
- neutrophil granulocytes = 40 - 70%
- eosinophil granulocytes = 2 - 4%
- basophil granulocytes = 0 - 1%
Which fluid compartments do also belong the group of interstitial fluid?
- bone
- dense connective tissue
What is transcellular fluid?
Examples.
body water found in epithelial lined compartments
- cerebrospinal fluid (liquor)
- ocular fluid
- synovia
- fluids in pleural cavity
- fluids in peritoneal cavity
Give values for [Na+] in ECF and ICF.
Give values for [K+] in ECF and ICF.
Give values for [Ca2+] in ECF and ICF.
Give values for [Cl-] in ECF and ICF.
Give values for [HCO3-] in ECF and ICF.
Give values for osmolality of ECF and ICF.
Give values for pH of ECF and ICF.
How is the volume of fluid compartments measured?
Examples.
dilution method
- known amount of tracer is added to a compartment
- tracer concentration is measured after sufficient time for uniform distribution throughout the compartment
- compartment volume calculated
* *V = amount of tracer/conc. of tracer**
List examples for tracers.
Function?
examples for tracers:
- total fluid: deuterium
- ECF: inulin
- blood plasma: protein, protein bound dye (Evans blue)
Differentiate btw lipid classes that can be found in the plasma membrane.
Where are the located, inner or outer leaflet?
What is their function?
Lipid-anchored membrane proteins are either … ?
- GPI-bound proteins, or
- bound to palmitoylated fatty acids
What is the difference btw channels and carriers?
Also refer to energetically transport mode, speed and kinetical properties.
- channel = gated, undergoes conf. change to open & close
- carrier = enzyme, undergoes conf. change to transport molecule from inside to outside, or vice versa
What is passive, primary, and secondary active transport?
- passive: along conc. gradient
- prim. active: transport against conc. gradient, directly coupled to hydrolysis of ATP
- sec. active: transport against electrochem. gradient, using energy of electrochem. gradient of other mol.
What does Fick’s first law state?
rate at which a molecule diffuses from point A to B
J = DA/Δx * Δc
- J = flux or rate of diffusion in [mol/sec]
- D = diffusion coefficient
- A = area across which diffusion is occurring
- Δc = concentration difference
- Δx = distance along which diffusion is occurring
The diffusion rate depends on… ?
- Δx = thickness of membrane
- Δc = conc. difference btw the 2 sides of the membrane, driving force
- D = diffusion coefficient (incorp. hydrophobicity + size of solute)
Which molecules are diffusible, partially diffusible, or non-diffusible through the plasma membrane?
- diffusible: gases (O2, CO, CO2, NO), hydrophobic molecules, hormones
- diffusible, using channels: water, ions, glucose
- non-diffusible: peptides, proteins, disaccharides
Give examples for different transporters used for facilitated transport.
- uniporter, e.g. GLUT-transporters
- symporters, e.g. Na/K/Cl cotransporter NKCC2 for concentrating urine in kidney (cf. picture for more)
- antiporters, e.g. Na-H exchanger NHE-1 to regulate pH (cf. picture for more)
Describe the structure of GLUT-transporters.
- 12 amphiphilic transmembrane proteins in plasma membrane
- hydrophobic ends binding outwards in plasma membrane, hydrophilic pocket formed inside
- N-, C-terminals in cytosol
→ conf. change transports glucose molecule
What is the difference btw GLUT 1, 2, and 4?
- GLUT 1: most common type, esp. in CNS and erythrocytes, high affinity for glucose, almost always saturated
- GLUT 2: e.g. in hepatocytes, small intestine, low affinity for glucose, hence gluc uptake dependent on blood sugar level → inhibits glycogen breakdown in liver
- GLUT 4: in adipocytes and skeletal muscle, insulin sensitive, high affinity, glucose is taken up if insuline level is high → lowers blood sugar
What is the inhibitor of Na+/K+ - ATPase?
quabain
What is the importance of CSTR?
Explain.
= cystic fibrosis transmembrane regulator
Cl- channel not coded in case of cystic fibrosis
→ defective epithelial transport, no mucus transport out of the lung
⇒ chronic lung infections, pancreatic insufficiency, infertility in males ⇒ death due resp. failure
What is driving force of water?
osmosis
→ water flows to where osmotic concentration is higher (↑ osmotic pressure)
What does van’t Hoff’s law state?
osmotic pressure is solely dependent on the number of molecules in the solution
→ it does not depend on size, mass, or chemical nature
π = nCRT
- π = osmotic pressure in [atm]
- n = no. of dissociable particles per molecule
- C = total solute conc.
- R = gas constant
- T = temperature in degrees Kelvin
What is the difference btw osmolarity and osmolality?
-
osmolarity = conc. * no. of dissociable particles
in [mOsm/l] - osmolality in [mOsm/kg]
⇒ osmolality is independent of temperature, hence the preferred term to describe biological systems
What is tonicity?
Classify.
effect of the solution on the volume of a cell
⇒ related to osmolality, but also considers ability of a mol. to cross the cell membrane
- hypotonic = causes a cell to swell
- isotonic = does not affect the volume of a cell
- hypertonic = causes a cell to shrink
What is described by the reflection coefficient?
Explain 2 related important terms.
reflection coefficient σ is a measure of the rel. ability of a molecule to cross the cell membrane
π = σ (nCRT)
- effective osmole: substance that is not able to cross the membrane, hence exert osmotic pressure
- ineffective osmole: substance that is able to cross the membrane, hence does not exert osmotic pressure
What is oncotic pressure?
osmotic pressure generated by large molecules (esp. proteins), bc pressure generated not conform w/ van’t Hoff’s law
Which organs are layered by epithelial cells?
- skin
- GI tract
- exocrine glands
- kidney
- lungs
- testes
What is the function of microvilli, sterocilia, and kinocilia?
- microvilli: incr. surface area
- stereocilia: incr. surface area
- stereocilia: transport mucus
+ diff. structural arrangement (cf. book)
What are different directions of cellular transport?
- excretion/secretion: interstitial → luminal
- re-/absorption: luminal → interstitial:
- vectorial/transcellular transport: through an epithelial cell
- paracellular transport: through space btw the cells (epithelium)
What is transcellular transport?
List important features.
transport across an epithelial cell
- 2 step process - uptake, transport out: 1 step usually passive (gradient), 1 active (pump)
- location of transporter (pumps, passive carriers, ion/water channels) on membrane domain depends direction
- needs energy (pump)
In which membrane domain is the Na+, K+ - ATPase located?
Any exceptions?
ALWAYS in basolateral membrane,
except: choroid plexus
List important features of paracellular transport.
Examples
transport through space btw epithelial cells that involves tight junctions
- passive
- can be selective
-
permeability of tight junctions often determines rate of transepithelial transport (high perm. → high rate), determined by claudins, i.e.
- prox. tubule of nephron, jejunum = leaky, high perm.
- collecting ducts, terminal portion of colon = tight, low perm.
What is ENaC?
What is it used for, which other channels are involved?
highly selective type of epithelial Na channel on apical surface
⇒ together w/ Na+/K+/ATPase and K+ channels (both on basolateral membrane) resp. for transcellular Na transport
Where does transepithelial Na transport happen?
- on frog skin
- distal tubule
- sweat glands
Describe the mechanism of transepithelial Na transport.
-
transcellular transport:
- Na+ diffuses through ENaC on apical surface into cell
- 3 Na+ pumped out, 2K+ pumped in, K+ diffuses out of cell involving Na+/K+/ATPase and K+ channels (both on basolat. surface)
-
paracellular transport:
- Cl- diffuses along conc. gradient into lume n
- H20 diffuses due to osm. pressure into lumen
⇒ water reabsorption in NaCl solution
Which substances regulate ENaC, hence reabsorption of water?
- modulated by aldosterone
- inhibited by amilorid (= diuretic agent)
Which components are involved in glucose reabsorption in the small intestine and proximal tubules?
- Na+/K+/ATPase
- channels (aquaporins, K+)
- cotransporter (SGLT 1/2)
- uniporter (GLUT-2)
What is the difference btw SGLT 1 and 2?
both present on luminal side of cell
- SGLT 1: in straight portion of prox. tubule, minor role
- SGLT 2: in prox. convoluted tubule, major role
Explain the mechanism of glucose reabsorption.
transcellular transport
- Na+ pumped out of, K+ pumped into cell, K+ diffuses out through channels (on basol. surf.)
- SGLT cotransports Na+, gluc along Na+ conc. gradient into cell on apical surf.
- GLUT-2 on basol. surface transports glucose into compartment
- H2O gets reabsorbed
Which components are involved in NaCl secretion in salivary glands and small intestine?
- Na+/K+/ATPase
- cotransporter (Na+/K+/Cl-)
- channels (K+, aquaporins, Cl-, e.g. CFTR)
- paracellular Na+, H20 transport
Explain the mechanism of NaCl secretion.
- Na+ pumped out of, K+ pumped into cell by the action of Na+/K+/ATPase, 2 Cl- cotransported w/ K+, Na+ into cell on basolat. surf.
- K+ diffuses out of cell on basolat. surf
- Cl- diffuses on apical surface out of cell through Cl- channels
- Na+, H20 diffuses due to osm. pressure and electrochem. gradient paracellularly into lumen
Where can H+ secretion be observed?
on parietal cells in stomach → secretion of HCl8
Explain the mechanism of HCl secretion in the stomach.
- metabolism:
CO2 + H2O → H2CO3 → H+ + HCO3- - H+ actively pumped out K+ pumped into, K+ diffuses out again (on apic. surf.)
- HCO3- transported out, Cl- transported into cell on basolat. surf.
- Cl- diffuses out of cell on apic. surf.
