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Physiology > 1.1 General principles + Energy Production > Flashcards

1.1 General principles + Energy Production Flashcards

1
Q

What are the major fluid compartments in the body and their relative percentage volumes?

A

In an average young adult male, 60% of body weight is water:
2/3 Intracellular - 40% body wt
1/3 ECF - divided into plasma 5% + interstitial fluid 15% body wt.

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2
Q

What is the mole? (mol)

A

Mole is SI unit for expressing amount of a substance

  • It is the molecular weight of the substance in grams
  • Each mol consists of 6x10^23 molecules - i.e. the gram weight of this number of molecules.
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3
Q

What is the dalton? (Da)

A

The dalton is the molecular weight of a substance, as a ratio of one twelfth the mass of atom of carbon-12.
The kDA=1000 Da, and is useful for expressing weight of proteins.

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4
Q

What is an equivalent? (eq)

A

for measuring electrical equivalence, given many solutes in the body are in form of charged particles.
1 eq = 1 mol of ionized substance / valence
e.g. 1 eq of Na+ = 23g / 1 = 23g.

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5
Q

Why is water an ideal solvent for physiological rxns?

A

H20 has a dipole moment where the oxygen pulls the electrons slightly away from the 2 H+ atoms -

  • creates charge separation that makes it POLAR, so
  • H20 can dissolve a variety of charge molecules
  • H20 molecules interact together via hydrogen bonding, which allows: 1) high surface tension, 2) high heat of vapourisation, 3) optimal conduction of current
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6
Q

What are electrolytes?

A

Electrolytes are molecules that dissociate in water to their cation (e.g Na+) and anion (Cl-) equivalents.
Key electrolytes are Na+, K+, Ca2+, Mg 2+, Cl-, HCO3-
which are distributed differently in the different body compartments (along with phosphates and proteins).

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7
Q

What is the pH?

A

pH is the negative logarithm to base 10 of [H+] -
e.g. for [H+] = 10^-7, pH = 7.
So for each pH unit, the [H+] is increased or decreased 10-fold.

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8
Q

What defines acids vs bases?

A

Acids are molecules that act as H+ donors in solution, bases tend to remove H+ from solutions

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9
Q

What is a strong vs weak acid/base?

A

Strong acids/bases dissociate completely in water (e.g HCL, NaOH) - i.e. cause a great change to the [H+]
Weak acids/bases dissociate partially - this is useful in physiological solutions for buffering.

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10
Q

What is a buffer?

A

A buffer is a substance that can bind or release H+ in solution, hence keeping the pH of a solution relatively constant. The Buffering Capacity of the body fluids is important for normal physiology.

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11
Q

What is the isohydric principle?

A

That all buffer pairs are in equilibrium with the same [H+]

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12
Q

What is an example of a physiological buffer?

A

Carbonic acid -
H2CO3 H+ + HCO3-
If H+ added to solution, equilibrium shifts left to remove H+, if OH- is added (binding H+ and removing it from the solution), the equilibrium shifts right i.e. dissociation to minimise change in [H+].

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13
Q

What is the Henderson Hasselbalch equation?

A

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

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14
Q

What is diffusion?

A

Diffusion is the process by which a gas or substance in solution expands, because of motion of its particles, to fill all of the available volume.

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15
Q

What is osmosis?

A

Osmosis is the diffusion of SOLVENT molecules (e.g. water), into a region where there is higher concentration of SOLUTE, to which the membrane is impermeable

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16
Q

What is the osmotic pressure?

A

The osmotic pressure is the pressure necessary to prevent solvent migration (i.e. applied to the region of greater solute concentration, to prevent osmosis)
In an ideal solution, osmotic pressure is related to temp + volume in same way as pressure of a gas:
P= nRT/V (n= number of particles, R is gas constant)

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17
Q

What is the osmole? (Osm)

A

Osmoles are used to express the concentration of osmotically active particles
1 Osm = gram-molecular weight of substance/number of freely moving particles that each molecule liberates in solution.
(mOsm = 1/1000 of 1 Osm)

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18
Q

What is osmolarity vs osmolality?

A

Osmolarity is number of osmoles / L of solution
Osmolality is number of osmoles / kg of solvent
Therefore osmolarity is affected by volume of various solutes in solution and temperature, but osmolality is not.

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19
Q

What is tonicity?

A

Tonicity is used to describe osmolality of a solution relative to plasma -
solutions with same osmolality are ISOTONIC
greater osmolality HYPERTONIC
lesser osmolality HYPOTONIC

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20
Q

What are the relative contribution of the plasma components to total osmolal concentration of plasma?

A

Plasma osmolarity = 290 mOsm/L
Majority is Na+, Cl- and HCO3- (~270 mOsm)
Other cations and anions make relatively small contribution.
Major non-electrolytes are glucose + urea (usually 5 mOsm each)

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21
Q

What formula can be used to estimate plasma osmolality?

A

Osmolality (mOsm/L) = 2[Na+] (mEq/L) + 0.055 [glucose] (mg/dl) + 0.36[BUN] (mg/dl)
(i.e. the constants convert units to mmol/L)

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22
Q

What is the equilibrium potential?

A

The equilibrium potential for an ion is the membrane potential at which influx and efflux are equal (i.e. balance of concentration gradient and electrical gradient)

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23
Q

How can we calculate equilbrium potential for an ion?

A

Usine a modified Nernst equation at 37 degrees-

E(Cl) = 61.5 log [Cli-]/[Clo-]

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24
Q

What are the intracellular and extracellular concentrations of key electrolytes, and their equilibrium potentials?

A

Na+ : 15 mmol/L inside, (140)150 mmol/L outside, +60mV
K+ : 150 inside, (3-5)5.5 outside, -90mV
Cl- : 9 inside, 125 outside, -70mV

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25
Q

How is the membrane potential generated?

A

The CONCENTRATION gradient of K+ facilitates it’s movement out of the cell via K+ channels, but the ELECTRICAL gradient is in the opposite direction –> an equilibrium is reached, and at that equilibrium there is slight excess of cations on outside and anions inside.
This is maintained by Na+ K+ ATPase, an ELECTROGENIC PUMP that pumps 2 K+ in and 3 Na+ out.

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26
Q

Which are the most prevalent cations and anions intracellularly and extracellularly?

A

Intracellular - K+ and prot-

Extracellular - Na+ and Cl-

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27
Q

ENERGY PRODUCTION

A

-

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28
Q

What are high energy phosphate compounds?

What is the most important of these?

A 
These are organic compounds which contain bonds between phosphoric acid residues - the bonds release high amounts of energy when hydrolysed (10-12 kcal/mol).
Adenosine triphosphate (ATP) - hydrolysis to ADP (and AMP) liberates energy
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29
Q

What is another example of a high energy compound (non-phosphate)?

A

The thioesters - Coenzyme A (CoA), reacts with acetic acid to form Acetyl-CoA which has a very high energy content.

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30
Q

What is oxidation and reduction?

A

Oxidation is combination of a substance with O2, or LOSS of H+ or e-
Reduction is gain of H+ or e-

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31
Q

What is the flavoprotein-cytochrome system?

A

A chain of enzymes that transfer H+ to oxygen, forming water. Each enzyme is reduced and then reoxidised as the H+ is passed down the line.
Occurs in the mitochondria.

32
Q

How is ATP formed?

A

Oxidative phosphorylation -

harnesses energy from proton gradient across the mitochondrial membrane to produce the high energy bond of ATP.

33
Q

What percentage of O2 consumption is mitochondrial?

A

90% in the basal state.

80% of this is coupled to ATP synthesis.

34
Q

MOLECULAR BUILDING BLOCKS

A

-

35
Q

What is the structure of a nucleoside?
How is a nucleotide different?
What do these molecules form?

A

A nucleoside contains a sugar (ribose or 2-deoxyribose) linked to nitrogen base/ring (purine or pyrimadine)
A nucleotide is a nucleoside + inorganic phosphate.
Form -
RNA, DNA, coenzymes + regulatory molecules e.g. NAD+, NADP+ and ATP!

36
Q

Where do the majority of purines + pyrimidines come from?

A

The majority are synthesised from amino acids in the liver.
(small amounts are absorbed from diet)
Those purines + pyrimidines released from nucleotide breakdown may be reused or catabolised.

37
Q

What are the major purines and pyrimidines?

A

Purines:
adenine
guanine
xanthine + hypoxanthine

Pyrimidines:
uracil
thymine
cytosine

38
Q

How are purines and pyrimidines catabolised?

A

Pyrimidines - to B-amino acids (i.e. amino group on the B carbon, not alpha) - then to CO2 + NH3
Purines - uric acid, excreted in urine.

39
Q

Describe the structure of DNA

A

Deoxyribonucleic acid -
two chains of nucleotides (bound with phosphodiester backbone) contain bases adenine, guanine, thymine + cytosine
stable DOUBLE HELIX - hydrogen bonding between AT and GC
The double helix is then compacted by associated with HISTONES, and then further into CHROMOSOMES (46 in diploid cell)

40
Q

What is a gene?

A

A fundamental unit of DNA - defined as the sequence of nucleotides that contains information required for production of an ordered amino acid sequence for a single polypeptide chain

41
Q

What is the typical structure of a gene?

A

5’ start - regulatory region - promoter - transcription start site - exons (translated) + introns (not translated) - polyA addition site - 3’ end

42
Q

What are alleles?

A

Alleles are versions of the same gene, occupying the same position on homologous chromosomes.
In diploid cells there will be 2 alleles for each gene.

43
Q

Briefly describe the cell cycle and somatic cell division.

A

G1 - gap 1 phase - cell growth
S - DNA synthesis phase
G2 - gap 2 - growth
M - mitosis:
- prophase - spindle formation, migration + attachment to chromosome centromeres
- metaphase - chromosome copies line up across equator of cell
- anaphase - centromeres break and chromosome copies are separated to opposite ends of cell
- telophase - chromosomes decondense, nuclear envelope reappears
- Cystokinesis

44
Q

How is the division process different for germ cells?

A

Germ cells undergo reductive division - meiosis
one of each pair of chromosomes goes to each mature germ cell - so each contains half the DNA of somatic cells (i.e. 46 to 23 chromosomes)
(when 2 germ cells unite in reproduction there is now 23+23=46 chromosomes)

45
Q

What is “ploidy”?

A

used to refer to number of chromosomes -
haploid - germ cells
diploid - somatic cells (euploid at rest, tetraploid just before division)
aneuploidy - cell contains other than haploid or exact multiple of it

46
Q

What is RNA? How does it differ from DNA?

A

Ribonucleic acid - single stranded, uracil in place of thiamine, sugar ribose in place of deoxyribose
DNA - Transcription via RNA polymerase - to mRNA, transfer tRNA, ribosomal rRNA, microRNAs other…
Various modifications e.g. splicing of pre-mRNA to mRNA + removal of introns, can produce multiple different mRNAs from single gene

47
Q

What is the main role of RNA in the cell?

A

Translation - protein synthesis.

tRNA delivers specific amino acids to the growing polypeptide chain at ribosome, based on mRNA sequences

48
Q

What are essential vs non-essential amino acids?

A

Essential must be obtained from diet
Non-essential are synthesised in vivo
Conditionally essential - histidine and arginine - must be nutritionally provided in times of rapid growth/recovery

49
Q

What is the amino acid pool?

A

Common amino acid pool supplies needs of body (proteins, creatine, purines/pyrimidines, hormones + neurotransmitters)
Contributed to by dietary proteins (digested into constituent AAs before absorption) + continuous hydrolysis + resynthesis of body proteins (80-100g/day!)

50
Q

Discuss protein structure

A

Proteins - made up of large numbers of AAs linked by peptide bonds (carboxyl-amino groups)
Smaller chains are peptides or polypeptides
Primary structure = order of AAs
Secondary structure = twisting and folding a-helix or B-sheet
Tertiary structure = arrangement of the above into layers, crystals or fibres
Quaternary structure = arrangement of multiple proteins as subunits of the functional structure

51
Q

Briefly explain protein synthesis

A

Protein synthesis = translation
In cytoplasm - AAs are ACTIVATED by combination with enzyme + AMP, then each binds to a specific tRNA
At ribosome -
mRNA attaches to 40S subunit, polypeptide chain is formed on the 60S subunit. tRNAs attach to both.
Codons = base triplets which each correspond to one AA
Start codon -> methionine AA, then one AA is added to the chain at a time –> stop codon.
Proteins then undergo post-translational modifications and transport/direction to functional state + location.

52
Q

Briefly outline protein degradation

A

Abnormal, aged or excess proteins are marked for degradation by UBIQUITINISATION
and are then degraded in PROTEASOMES or LYSOSOMES

53
Q

Briefly outline amino acid catabolism

A

1) Amino acids undergo transamination reactions in the citric acid cycle, where they can contribute to gluconeogenesis.
2) Oxidative deamination occurs in the liver - dehydrogenation:
AA + NAD+ –> Imino acid + NADH + H+
and hydrolysis:
Imino acid + H2O –> keto acid + NH4+

54
Q

What happens to NH4+ from deamination of amino acids?

A

Most NH4+ is converted to urea (the urea cycle) which is then excreted in the urine.
Urea formation occurs in the liver - in severe liver disease BUN falls and NH3 rises

55
Q

Describe the structure of carbohydrates?

A

Organic molecules with equal amount of C + H2O
Monosaccharides (pentoses e.g. ribose, hexoses e.g. glucose, fructose, galactose)
Disaccharides e.g sucrose, lactose
Polysaccharides

56
Q

What are the varied roles of carbohydrates?

A

Structural e.g. nucleotides, other
Functional e.g. signalling glycoproteins/receptors
Energy production and storage

57
Q

What happens to glucose when it enters cells?

A

Glucose is phosphorylated to G-6-phosphate by hexokinase (or glucokinase in liver - upregulated by insulin)
Then, G-6-P either catabolized (GLYCOLYSIS), or polymerised to glycogen (GLYCOGENESIS)

58
Q

What is glycogen?

A

Storage form of glucose, largely in liver and skeletal muscle. Glycogenlysis is term for glycogen breakdown

59
Q

What is gluconeogenesis?

A

Conversion of non-glucose molecules to glucose, via citric acid cycle, and from lactate->pyruvate.

60
Q

What about conversion of glucose to fats?

A

This can occur via conversion through pyruvate and acetyl-CoA, but is irreversible.

61
Q

Briefly describe the citric acid cycle

A

Sequence of reactions in which acetyl-CoA is metabolised to CO2 + H20
Common pathway for oxidation of carbohydrates, fats + some amino acids
multiple entry points especially for amino acids via deamination
Cyclical - regenerates oxaloacetate
Generates energy - GTP

62
Q

How much energy is generated during anaerobic vs aerobic glycolysis?

A

Anaerobic - 2 ATP

Aerobic - 38 ATP

63
Q

What is normal plasma glucose level in peripheral venous blood?

A

3.9-6.1 mmol/L = 70-110 mg/dl

64
Q

What factors determine plasma glucose level?

A

Balance of glucose entering and leaving bloodstream:
dietary intake
rate of entry into myocytes, adipose tissue, brain etc
glucostatic activity of liver

Liver converts 5% ingested glucose to glycogen + 30-40% to fat, remained metabolised in muscle + other tissues.
Fasting - liver breaks down glycogen
Prolonged fasting - gluconeogenesis from AAs + glycerol in liver
HypERglycaemia –> glycosuria when BGL > 10mmol/L (180mg/dl)

65
Q

What are the 4 main groups of lipids?

A

Fatty acids - saturated or unsaturated
Triglycerides - esters of glycerol + 3 FAs
Phospholipids - esters of glycerol + 2 FAs + phosphate +/- other - cell membranes + signalling
Sterols - cholesterol + derivatives - steroid hormones, bile acids, vitamins

66
Q

How are fatty acids broken down in the body?

A

FAs are broken down to acetyl-CoA which enters citric acid cycle
B-oxidation in MITOCHONDRIA = serial removal of 2 CARBON fragments
Short + medium chain FAs enter easily, long-chain FAs require ester bond to carnitine to cross inner mitochondrial membrane
BIG energy production - 44 mol ATP (compared 38 mol ATP / mol glucose)

67
Q

How are ketone bodies formed?

A

Acetoacetate, B-hydroxybutyrate + acetone = ketone bodies

Acetoacetate (B-keto acid) is formed in the liver from condensed acetyl-CoA + another pathway
Converted to B-hydroxybutyrate + acetone - not metabolised well by liver, so diffuse into circulation.

Ketone bodies are metabolised via various pathways, and acetone is discharged in urine and expiration.

68
Q

What is ketoacidosis?

A

Ketone bodies are normally metabolised as rapidly as they are formed.
If there is decreased glucose metabolism –> insufficient supply of products for citric acid cycle + acetyl-CoA acculumulates and forms acetoacetate.

When tissue ability to oxidise ketones is exceeded, they accumulate in bloodstream (ketosis).
Acetoacetate + B-hydroxybutyrate are anions of moderately strong acids which are usually buffered - when buffering capacity is exceeded –> metabolic acidosis.

Results from deficient intracellular glucose - in starvation, DM or HFLC diet.

69
Q

What are the 2 main types of cellular lipids?

A

1) Structural lipids - membranes + cellular signalling molecules - preserved in starvation
2) Neutral fat - stored in adipose cells - metabolised in starvation
( 3) - Brown fat - more abundant in infants - contain an uncoupled proton conductance/ “short-circuit” to generate heat instead of ATP )

70
Q

How are lipids transported in the plasma?

A
  • relatively insoluble in aqueous solution, therefore protein bound:
    Albumin - FFAs
    Lipoprotein - cholesterol, triglycerides, phospholipids
    Lipoproteins travel from intestine to liver via EXogenous pathway / between other tissues via ENDogenous pathway
71
Q

What are the 6 types of lipoprotein?

A

From lowest density (highest lipid content) -
Exogenous system:
chylomicrons
chylomicron remnants

Endogenous system:
VLDL
IDL
LDL - delivers cholesterol to peripheral tissues
HDL - removes cholesterol from peripheral tissues, to liver

72
Q

How are dietary lipids absorbed?

A

Processed by pancreatic enzymes in the SI to form mixed micelles - taken up into intestinal mucosal cells where chylomicrons are formed –> then transported via exogenous pathway in lymphatics to enter circulation.
Lipoprotein lipase breaks down the lipids from the chylomicron, and lipids enter the adipose cells.

73
Q

Describe FFA metabolism

A

In addition to exogenous + endogenous pathways, FFAs are synthesised in fat depots, circulate bound to albumin and are major energy source for many organs, especially the heart.
The above is triggered by hormone-sensitive lipase which catalyzes breakdown of stored triglycerides.
(Lipoprotein lipase is opposite - removes the FFAs from chylomicrons for their conversion to triglycerides)

74
Q

What is cholesterol important for? How is it absorbed and synthesised?

A

precursor of steroid hormones + bile acids + constituent of cell membranes
absorbed in SI into chylomicrons in mucosa
transported via chylomicron remnants to liver.
Liver also synthesises cholesterol from acetyl-CoA -> acetoacetyl-CoA -> HMG-CoA –> mevalonic acid -> squalene -> cholesterol

Statins inhibit HMG Co-A reductase

75
Q

What are eicosanoids?

A 
Substances originating from arachidonic + linoleic acid
prostaglandinds
thromboxanes
prostacyclin
leukotrienes
lipoxins
the "local hormones"

Physiology (9 decks)

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