Physiology 2 Flashcards
What type of bonds link the individual amino acids in a protein sequence?
Covalent peptide bonds
What are the two most common secondary structures of proteins?
Alpha helix
Beta pleated sheet
What type of bonds produce a protein’s secondary structure?
Hydrogen bonds
What type of bonds produce a protein’s tertiary structure?
Hydrogen bonding
Ionic bonding
Hydrophobic interactions
Covalent disulphide bonding (cysteine)
Contrast the ‘lock and key’ and the ‘induced fit’ models of enzymatic action
Lock and key requires ‘perfect fit’
Induced fit suggests conformational change of the enzyme occurs as a result of the substrate.
Name some metal ion co-factors for enzymatic reactions and their associated enzymes
Mg2+: Hexokinase
Zn2+: Carbonic anhydrase
Fe2+: Cytochrome oxidase
Name some organic co-enzymes and their associated reactions
Co-enzyme A: Acyl group reactions
Co-enzyme B12: Alkyl group reactions
What effect does temp have on rate of enzymatic reaction?
Increased temp -> increased rate until enzyme denatured
What effect does pH have on rate of enzymatic reaction?
Enzymes are pH-specific. H+ ion concentration affects Hydrogen bonding and amino acid charge leading to conformational change.
Michaelis-Menten equation?
V0 = Vmax[S] / Km + [S]
Where V0=initial reaction velocity
Vmax=max velocity
Km=Michaelis constant
[S]=substrate constant
How is the Michaelis constant derived?
k-1 + k2
/ k1
E + S -> ES (k1)
ES -> E + P (k2)
ES -> E + S (k-1)
What happens to the Lineweaver-Burke slope when a competitive inhibitor is added to an enzymatic reaction?
Increase in slope around 1/Vmax (point of crossing y-axis)
What happens to the Lineweaver-Burke slope when a non-competitive inhibitor is added to an enzymatic reaction?
Increase in slope from -1/Km (where meets x-axis)
Define an allosteric enzyme
Enzyme that has multiple subunits and exhibits conformational change (and subsequent effects on substrate binding) in the presence of additional molecules
What effect does allosteric binding have on Michaelis-Menten characteristics?
The hyperbolic curve is replaced by a sigmoid curve.
Outline the fluid compartments of the body
70kg male (standard)
60% water - 42L
2/3 ICF - 28L
1/3 ECF - 14L
In the ECF: Intravascular - 4L (9.5%) Interstitial - 9L (21%) Transcellular - 1L (2%) Bone/connective tissue - 1L (2%)
How much of the intravascular volume is accounted for by plasma?
55%
What is an approximate calculation for total intravascular volume?
70-75ml/Kg
Contrast osmolality and osmolarity
Osmolality: osmol/Kg water
Osmolarity: osmol/L water (temperature dependent)
What is a normal plasma osmolality?
280-305 mOsmol/Kg
How does osmolality relate between body water compartments?
Is is equal across compartments due to free movement of water across membranes
Formula for estimating plasma osmolality?
= Urea + K + 2Na
Where are osmoreceptors found?
Hypothalamus
What features of capillaries make them effective vessels for exchange?
- Low flow velocity (0.05-0.1cm/s)
- Large area for diffusion
- Thin walls (to minimise diffusion distance)
What is the structure of a capillary?
Endothelial tube
Basal lamina
Average diameter 5-9 um
What types of capillary exist?
Continuous
Fenestrated
What are the subtypes of continuous capillary?
- Typical
- Tight junctions (eg. BBB)
- Discontinuous/sinusoidal (liver)
Where are fenestrated capillaries found?
Endocrine organs Choroid plexus Glomerular capillaries GI tract Hypothalamus
Size of molecules filtered by glomerular apparatus?
<4nm freely filtered
>8nm excluded
What are the functions of the capillary and venular pericytes?
- Contractile alteration of luminal diameter
- Production of basement membrane and extracellular matrix
- Release vasoactive agents
- Regulate flow through endothelial cell junctions
Define vasomotion
Vasomotion is the cycling of contraction and relaxation controlled by a smooth muscular response to local metabolites.
What factors affect capillary sphincter tone?
NO low pO2 or high pCO2 Raised temperature Rising [K+] or [H+] Lactic acid Prostocyclin, thromboxane, endothelins
What is the Starling equilibrium equation?
Q (fluid movement) = KA[Pc-Pi0 - s(PIc-PIi)]
Where: K=permeability constant A=area of membrane Pi=interstitial hydro press Pc=capillary hydro press s=albumin reflection coeff. PIi=interstitial oncotic press PIc=capillary oncotic press
Why do alveoli not fill with water?
Hydrostatic pressure in the capillaries of the lung is less than colloid osmotic pressure, hence osmotic pressures prevent water entering the alveolus
What factors may lead to development of oedema?
Excess capillary filtration (increased osmotic gradient)
Protein deficiency
Increased capillary leak
What substances increase capillary permeability?
Substance P Histamine IL1, IL4, IL6 Kinins eg bradykinin, Kallidin Burns Acute lung injury Reperfusion injury
What is meant by the term transcytosis?
The movement of extracellular material through a cell using vesicles, comprising endocytosis on one surface of the cell and exocytosis on another
Which three proteins are important for transcytosis?
Caveolin: Involved in protein endocytosis
Clathrin: stabilises vesicular structure
Dynamin: ‘Pinches off’ the vesicle forming spherical structures
Which electrolyte does exocytosis rely upon?
Calcium
Also requires ATP
Explain the Gibbs-Donnan effect
Proteins exert the effect of binding permeable ions eg. albumin binding Na and Cl, which increases the colloid osmotic pressure.
What is the Nernst equation?
Calculates the equilibrium potential across a membrane
E = RT ln (c1/c2) + Zfv
Where E: electrochemical potential in joules/mol
R: universal gas constant (8.31 J/K/mol)
T: Absolute temp (K)
c1, c2: osmolarity of compartments (c1>c2)
Z: valence of ion
f: Faraday constant (96500 C/mol)
v: volts (J/coulomb)
What is the rearranged Nernst equation?
Eion = 61.5 log [ion1]/[ion2]
at 37 degrees C
What is the Goldman equation?
Calculates the membrane potential taking into account the contributions of multiple diffusible ions.
V = RT/F ln ((Pk[k]o + Pna[na]o + Pcl[cl]i) / Pk[k]i + Pna[na]i + Pcl[cl]o))
Describe the structure of lymphatic vessels
Begin as blind-ended tubes close to capillaries in the interstitial space.
Extremely thin endothelial lining and incomplete or absent basement membrane.
Collagenous anchoring fibrils exert radial traction keeping lumen open in the interstitial space.
Larger lymph vessels resemble venules and veins, with smooth muscle, elastin and collagenous walls.
How is the flow of lymph fluid maintained?
Relies on hydrostatic pressure gradient
Peristalsis of lymph vessels
Large vessels have valves
Aided by:
-Negative intrathoracic pressure during respiration
-Suction effect of high velocity flow at terminal junction with brachiocephalic veins
How long is the thoracic duct in an adult?
~45cm
Into which lymph nodes do the following organs drain? Abdominal wall Intestines Adrenals/gonads/posterior abdo wall Liver Pelvic viscera/perineum/lower limb
Abdominal wall: Axillary, anterior mediastinal, superficial inguinal
Intestines: Preaortic
Adrenals/gonads/post wall: Paraaortic
Liver: Superficial + deep plexi -> anterior and posterior mediastinal
Pelvis/perineum/legs: Iliac -> paraaortic
What is the protein content of hepatic lymph drainage?
6.2 g/dL
Lower than plasma (7g/dL) but higher than other tissues eg. heart (4.4 g/dL), GIT (4.1 g/dL), lung (4 g/dL), skin + skeletal muscle (2 g/dL)
What factors are most important in determining absorption of water-soluble substances in the gut?
Concentration gradient
Diffusion distance
How is fat absorbed in the intestine?
Large molecules emulsified by bile salts + lecithin -> droplets 0.5-1 um
Lipase + colipase + droplets -> FFA + 2-monoglycerides
Micelles formed containing ~20 fat molecules
monoglycerides absorbed passively, FFA may be transported by fatty acid transport proteins (eg. FATP4)