W1 - Cellular physiology (1.1)

Question 1

What percentage of the total body weight is water in an adult?

Classify + values.

Answer 1

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}

Question 2

What is the total blood volume of the body?

Constituents.

Answer 2

∽ 5l (water)

• ∽ 3l plasma (ECF)
• ∽ 2l in cells (ICF)

→ seperated by capillary blood cell membrane

Question 3

What is measured for a complete blood count?

Values.

Answer 3

• 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

Question 4

Which fraction is described by the hematocrit?

Values.

Answer 4

volume percentage of red blood cells in blood

• men: 40 - 52% (∽ 45%)
• women: 37 - 48% (∽ 40%)

Question 5

What are the percentages of different WBC types?

Answer 5

• lymphocytes = 25 - 30%
• monocytes = 4 - 8%
• neutrophil granulocytes = 40 - 70%
• eosinophil granulocytes = 2 - 4%
• basophil granulocytes = 0 - 1%

Question 6

Which fluid compartments do also belong the group of interstitial fluid?

Answer 6

• bone
• dense connective tissue

Question 7

What is transcellular fluid?

Examples.

Answer 7

body water found in epithelial lined compartments

• cerebrospinal fluid (liquor)
• ocular fluid
• synovia
• fluids in pleural cavity
• fluids in peritoneal cavity

Question 8

Give values for [Na⁺] in ECF and ICF.

Answer 8

Question 9

Give values for [K⁺] in ECF and ICF.

Answer 9

Question 10

Give values for [Ca²⁺] in ECF and ICF.

Answer 10

Question 11

Give values for [Cl^-] in ECF and ICF.

Answer 11

Question 12

Give values for [HCO₃^-] in ECF and ICF.

Answer 12

Question 13

Give values for osmolality of ECF and ICF.

Answer 13

Question 14

Give values for pH of ECF and ICF.

Answer 14

Question 15

How is the volume of fluid compartments measured?

Examples.

Answer 15

dilution method

1. known amount of tracer is added to a compartment
2. tracer concentration is measured after sufficient time for uniform distribution throughout the compartment
3. compartment volume calculated
   * *V = amount of tracer/conc. of tracer**

Question 16

List examples for tracers.

Function?

Answer 16

​examples for tracers:

• total fluid: deuterium
• ECF: inulin
• blood plasma: protein, protein bound dye (Evans blue)

Question 17

Differentiate btw lipid classes that can be found in the plasma membrane.

Where are the located, inner or outer leaflet?

What is their function?

Answer 17

Question 18

Lipid-anchored membrane proteins are either … ?

Answer 18

• GPI-bound proteins, or
• bound to palmitoylated fatty acids

Question 19

What is the difference btw channels and carriers?

Also refer to energetically transport mode, speed and kinetical properties.

Answer 19

• channel = gated, undergoes conf. change to open & close
• carrier = enzyme, undergoes conf. change to transport molecule from inside to outside, or vice versa

Question 20

What is passive, primary, and secondary active transport?

Answer 20

• 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.

Question 21

What does Fick’s first law state?

Answer 21

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

Question 22

The diffusion rate depends on… ?

Answer 22

• Δx = thickness of membrane
• Δc = conc. difference btw the 2 sides of the membrane, driving force
• D = diffusion coefficient (incorp. hydrophobicity + size of solute)

Question 23

Which molecules are diffusible, partially diffusible, or non-diffusible through the plasma membrane?

Answer 23

• diffusible: gases (O₂, CO, CO₂, NO), hydrophobic molecules, hormones
• diffusible, using channels: water, ions, glucose
• non-diffusible: peptides, proteins, disaccharides

Question 24

Give examples for different transporters used for facilitated transport.

Answer 24

• 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)

Question 25

Describe the structure of GLUT-transporters.

Answer 25

* **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

Question 26

What is the difference btw GLUT 1, 2, and 4?

Answer 26

* **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

Question 27

What is the inhibitor of Na⁺/K⁺ - ATPase?

Answer 27

**quabain**

Question 28

What is the importance of CSTR? Explain.

Answer 28

= **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

Question 29

What is driving force of water?

Answer 29

**osmosis** → water flows to where osmotic concentration is higher (↑ osmotic pressure)

Question 30

What does van't Hoff's law state?

Answer 30

**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

Question 31

What is the difference btw osmolarity and osmolality?

Answer 31

* **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

Question 32

What is tonicity? Classify.

Answer 32

**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

Question 33

What is described by the reflection coefficient? Explain 2 related important terms.

Answer 33

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**

Question 34

What is oncotic pressure?

Answer 34

**osmotic pressure generated by large molecules** (esp. proteins), bc pressure generated not conform w/ van't Hoff's law

Question 35

Which organs are layered by epithelial cells?

Answer 35

* **skin** * **GI tract** * **exocrine glands** * **kidney** * **lungs** * **testes**

Question 36

What is the function of microvilli, sterocilia, and kinocilia?

Answer 36

* *_microvilli:_* **incr. surface area** * *_stereocilia:_* **incr. surface area** * *_stereocilia:_* **transport mucus** ​+ diff. structural arrangement *(cf. book)*

Question 37

What are different directions of cellular transport?

Answer 37

* **excretion/secretion:** interstitial → luminal * **re-/absorption:** luminal → interstitial: * **vectorial/transcellular transport:** through an epithelial cell * **paracellular transport:** through space btw the cells (epithelium)

Question 38

What is transcellular transport? List important features.

Answer 38

​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)

Question 39

In which membrane domain is the Na⁺, K⁺ - ATPase located? Any exceptions?

Answer 39

ALWAYS in **basolateral membrane**, except: choroid plexus

Question 40

List important features of paracellular transport. Examples

Answer 40

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.

Question 41

What is ENaC? What is it used for, which other channels are involved?

Answer 41

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

Question 42

Where does transepithelial Na transport happen?

Answer 42

* on frog skin * distal tubule * sweat glands

Question 43

Describe the mechanism of transepithelial Na transport.

Answer 43

1. _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) 2. _paracellular transport:_ * Cl^- diffuses along conc. gradient into lume n * H₂0 diffuses due to osm. pressure into lumen ⇒ **water reabsorption in NaCl solution**

Question 44

Which substances regulate ENaC, hence reabsorption of water?

Answer 44

* modulated by **aldosterone** * inhibited by **amilorid** (= diuretic agent)

Question 45

Which components are involved in glucose reabsorption in the small intestine and proximal tubules?

Answer 45

* **Na⁺/K⁺/ATPase** * **channels** (aquaporins, K⁺) * **cotransporter** (SGLT 1/2) * **uniporter** (GLUT-2)

Question 46

What is the difference btw SGLT 1 and 2?

Answer 46

​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

Question 47

Explain the mechanism of glucose reabsorption.

Answer 47

transcellular transport 1. Na⁺ pumped out of, K⁺ pumped into cell, K⁺ diffuses out through channels (on basol. surf.) 2. SGLT cotransports Na⁺, gluc along Na⁺ conc. gradient into cell on apical surf. 3. GLUT-2 on basol. surface transports glucose into compartment 4. H₂O gets reabsorbed

Question 48

Which components are involved in NaCl secretion in salivary glands and small intestine?

Answer 48

* **Na+/K+/ATPase** * **cotransporter** (Na⁺/K⁺/Cl^-) * **channels** (K⁺, aquaporins, Cl^-, e.g. CFTR) * **paracellular Na⁺, H20 transport**

Question 49

Explain the mechanism of NaCl secretion.

Answer 49

1. 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. 2. K⁺ diffuses out of cell on basolat. surf 3. Cl^- diffuses on apical surface out of cell through Cl^- channels 4. Na⁺, H₂0 diffuses due to osm. pressure and electrochem. gradient paracellularly into lumen

Question 50

Where can H⁺ secretion be observed?

Answer 50

on **parietal cells in stomach** → secretion of HCl8

Question 51

Explain the mechanism of HCl secretion in the stomach.

Answer 51

1. metabolism: CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃^- 2. H⁺ actively pumped out K⁺ pumped into, K⁺ diffuses out again (on apic. surf.) 3. HCO₃^- transported out, Cl^- transported into cell on basolat. surf. 4. Cl^- diffuses out of cell on apic. surf.