VIVA: Physiology - Principles of cellular function

Question 1

How is water distributed through the body compartments?

Answer 1

TBW is 60% of body weight (42L in 70kg person)
ICF is 2/3 TBW (28L)
ECF is 1/3 of TBW (14L): 3/4 interstitial (10.5L), 1/4 plasma (3.5L)

Question 2

How do age and gender affect total body water?

Answer 2

TBW decreases with age, and is higher in males

Question 3

What are the buffer systems in blood?

Answer 3

1. Bicarbonate buffer system*
2. Plasma proteins:
   - Free carboxyl and amino groups
   - Includes albumin
3. Hb
   - Imidazole groups of histidine residues
   - Deoxygenated Hb is a more efficient buffer than HbO2 (greater affinity for CO2; Haldane effect)

• needed to pass + one other

Question 4

Explain how carbonic acid / bicarbonate system works

Answer 4

HCO3- + H+ <-> H2CO3 <-> H2O + CO2

Can be catalysed in both directions by the intracellular enzyme carbonic anhydrase, which increases the speed of the reaction

Acid-base balance maintained physiologically by respiratory and renal systems: pCO2 altered by changes in ventilation, pHCO3 altered by changes in renal filtration

Question 5

What are the major intracellular buffer systems?

Answer 5

1. Proteins
2. Phosphate:
   - H2PO4(2-) <-> H+ + HPO4-

Question 6

Describe the Henderson-Hasselbach equation

Answer 6

pH = pKa + log [A-] / [HA]

Describe the relationship between the pH of a weak acid to its acid dissociation constant (pKa) and the ratio between the concentration of an acid and its conjugate base in equilibrium

Question 7

Outline the different ways in which a substance can cross a cell membrane

Answer 7

3 needed to pass:

Passive:
- Passive diffusion (including osmosis)
- Facilitated diffusion (via specialised membrane channels)

Active:
- Endo/exocytosis
- Ion channels (e.g. ligand-, voltage- and mechanical-gated)
- Active transport (may be primary or secondary / co-transport)

Question 8

Explain the process of secondary active transport and give an example

Answer 8

When the primary active transport of a substance against its electrochemical gradient facilitates the secondary movement of a substance down its electrochemical gradient

E.g. Na+ / glucose (cotransport), Na+ / amino acids, Na+ / Ca2+ and H+ (counter-transport)

Question 9

Describe the function of the sodium-potassium pump

Answer 9

Energy-dependent antiport found in cell membranes
Catalyses hydrolysis of ATP to ADP to drive movement of 3 Na+ out of the cell in exchange for 2 K+ into the cell
Maintains electrochemical gradient of the ECF, and is a large part of the basal energy consumption in humans (accounts for 33% of a cell’s energy use, 70% in neurons)
Often coupled to the transport of other substances (secondary active transport, e.g. glucose)

Question 10

Describe the synthesis and metabolism of cAMP

Answer 10

2/3 to pass:
- Formed inside the membrane
- ATP is converted to cAMP via adenylyl cyclase
- Metabolised to AMP by phosphodiesterase

Question 11

Discuss the function of cAMP

Answer 11

Acts as an intracellular second messenger
Activates an intracellular enzyme system (e.g. in the neuron)
Stimulates protein synthesis

Question 12

What are the major factors determining the plasma glucose?

Answer 12

Balance between glucose entering the bloodstream and leaving the bloodstream, affected by:
- Dietary intake
- Cellular uptake (especially skeletal muscle, adipose cells, hepatocytes)
- Hepatic glucostasis (glycogenesis, glycogenolysis, gluconeogenesis)
- Renal filtration (freely filtered by >99% reabsorbed in PCT to Tmax)
- Hormonal effects on these processes (particularly cell uptake and hepatic metabolism)

• needed to pass + 3 others

Question 13

List hormones which affect plasma glucose levels?

Answer 13

Decreases BSL*:
- Insulin
- IGF-1 and IGF-2

Increases BSL*:
- Catecholamines
- Glucagon
- Growth hormone
- Cortisol
- Thyroid hormones

• 3 examples needed to pass + effects on BSL

Question 14

What are the potential pathways for glucose metabolism in the body?

Answer 14

1. Aerobic and anaerobic glycolysis:
   - Produces pyruvate, energy used to form ATP)
2. Pentose phosphate pathway
   - Parallels glycolysis
   - Produces nucleotide/AA precursors and reducing equivalents in the form of NADPH
3. Glycogenesis

Question 15

What are the types of immunoglobulin and the clinical significance of each?

Answer 15

3/5 to pass:
1. IgA:
- Secretory
- In mucous membranes mainly in respiratory and GI tracts
- Also secreted in breastmilk and crosses placenta (passive immunity for newborns)
2. IgD:
- Antigen recognition by B cells
3. IgE:
- Role in allergy and anaphylaxis, also in parasite and helminth infections
- Induces release of histamine from basophils and mast cells
4. IgG:
- Role in complement activation and opsonisation, important for response to infection
- Most common immunoglobulin, some delay in production during infection
5. IgM:
- First Ig to be produced in response to infection
- Role in complement activation

Question 16

What are the features of innate and acquired immunity?

Answer 16

Innate immunity:
- Triggered by cellular receptors (e.g. toll-like receptors)
- Bind molecular sequences common on microorganisms (not in eukaryotic cells)
- Activate defence mechanisms (e.g. interferons, phagocytosis, production of antibacterial peptides, complement activation, proteolytic cascades)
- Important in early response to infection

Acquired immunity:
1. T-lymphocytes:
- Cell-bound receptors related to antibody molecules
- Encounter cognate antigen, and proliferate and produce cytokines to orchestrate immune response (including activation of B lymphocytes)
2. B lymphocytes:
- Form clones to produce antibodies
3. Memory cells:
- Small number of T and B lymphocytes persist post antigen exposure
- Second exposure to same antigen provokes prompt and magnified immune attack

Question 16

Draw a typical immunoglobulin molecule and label the parts

Answer 16

Needed to pass:
- Light chain
- Heavy chain

Question 17

How do cells communicate to one another?

Answer 17

3/6 to pass:
1. Gap junctions: direct cell-to-cell communication
2. Synaptic: via neurotransmitters in ECF
3. Paracrine: via diffusion of chemical messengers to neighbouring cells
4. Autocrine: via diffusion of chemical messengers that act on the cell itself
5. Endocrine: via hormones in circulating body fluids
6. Juxtacrine: molecules on cell membrane attach to another cell membrane (e.g. TGF repeats on membrane of one cell bind to TGF receptors on neighbouring cell)

Question 18

How do receptors respond to variations in messengers?

Answer 18

Receptors change with physiological variation:
- Receptors downregulated in response to excess messenger
- Upregulated in response to decrease in messenger
- Exception is angiotensin II in adrenal cortex

Question 19

How do chemical messengers act on cells?

Answer 19

Via:
1. Ion channel activation (e.g. ACh, nicotinic, NA)
2. G-protein activation (e.g. adrenaline, NA, dopamine, histamine, AT II):
- May result in increased production of second messengers including cAMP (e.g. NA) or cGMP
3. Direct activation of transcription of mRNA (e.g. steroid hormones, thyroid hormone)
4. Activation of enzyme activity:
- E.g. AT II activates phospholipase C , insulin activates tyrosine kinase, TGF increases activates serine/threonine kinase

Question 20

Name the principal ketone bodies

Answer 20

2/3 to pass:
- Acetoacetate
- B-hydroxybutyrate
- Acetone

Question 21

How are ketone bodies produced and how are they metabolised?

Answer 21

Production:
- Occurs in mitochondria, mainly in hepatocytes
- B oxidation of fatty acids produces acetyl CoA*
- Under normal conditions, acetyl CoA is further oxidised via the citric acid cycle in a high energy yield process
- If the amount of acetyl CoA produced exceeds the capacity of the citric acid cycle, acetyl CoA units condense to form acetoacetyl CoA, which is then metabolised to form ketone bodies

Metabolism:
- In the liver: acetoacetyl CoA -> acetoacetate -> B-hydroxybutyrate and acetone, which are excreted in the urine and with respiratory
- In the tissues: succinyl CoA -> acetoacetate -> CO2 and H2O via citric acid cycle

• needed to pass

Question 22

In which clinical situations do ketones accumulate in the body?

Answer 22

• Diabetic ketoacidosis
• Alcoholic ketoacidosis
• Starvation ketosis
• High fat low carbohydrate diet (ketogenic)

Question 23

Describe the structure of the sodium potassium pump

Answer 23

Has heterogenous transmembrane alpha and beta subunits:
- a subunit has intracellular binding sites for Na+ and ATP, and extracellular binding sites for K+ and ouabain
- a subunit also has intrinsic ATPase activity
- B subunit has no binding sites

When Na+ binds to alpha subunit, ATP also binds and is converted to ADP causing a change in protein configuration which extrudes Na+ out of the cell

K+ then binds extracellularly dephosphorylating the alpha subunit which returns to its original configuration, and releasing K+ into the cytoplasm

Question 24

What is normal serum osmolality?

Answer 24

290 mOsm/L

Question 25

What substances contribute to serum osmolality?

Answer 25

Principally (all but 20 mOsmols) the ions (Na+ *, K+ *, Cl-, HCO3)
Rest is other cations and anions, urea, and glucose
Much less so proteins (due to high molecular weight)
Possibly alcohols or mannitol

• needed to pass + one other

Question 26

How does plasma differ in composition to intracellular fluid?

Answer 26

Intracellular has higher concentration of K+, proteins* and phosphates; and lower concentrations of Na+, Cl- and HCO3-

*needed to pass

Question 27

What is the difference between diffusion and osmosis?

Answer 27

Diffusion:
- Net flux of solute* particles down a concentration gradient (from area of high to low concentration)
- Time to equilibrium is proportional to square of the distance
- Rate of diffusion is proportional to cross-sectional area and gradient (Fick’s law)

Osmosis:
- Net flux of solvent* across a membrane to an area of higher concentration of solute to which the membrane is impermeable
- Osmotic pressure is calculated by nRT/V

• needed to pass

Question 28

Define tonicity

Answer 28

Osmolality of a solution relative to plasma
E.g. 0.9% saline is isotonic (actually slightly hypertonic)

Question 29

What is the genesis of the membrane potential?

Answer 29

Differences in concentration gradient* and electrical gradient* of the major cations (Na+ and K+) across the impermeable cell membrane
Established and maintained by Na+ / K+ ATPase (3 Na+ out for 2 K+ in, so electrogenic)

Question 30

What are the phases of protein synthesis?

Answer 30

1. Transcription of mRNA*
2. Post-transcriptional modification of mRNA
3. Translation of mRNA* to amino acid chain along a ribosome* using tRNA
4. Post-translational modification of the protein in the endoplasmic reticulum (by hydroxylation, carboxylation, glycosylation, phosphorylation, cleavage and folding)

• needed to pass

Question 31

Describe the process of secretion of proteins from cells

Answer 31

Polypeptide sequences are cleaved off (e.g. prohormones to hormones)
Some proteins have leader sequences that target the endoplasmic reticulum and are secreted by exocytosis
Others are secreted from cytoplasm via ATP-dependent membrane transporters