Homeostasis & cell biology

Define physiology.

Branch of biology that deals with the normal functions of living organisms and their parts; the way in which a living organism or bodily part functions.  

Physiology reflects much of conscious perception of internal and external world.  

External: changes in temperature, or senses. 

Internal: increases in heart & breathing rate during exercise, or pounding of heart when scared.  

Define homeostasis.

The maintenance of the internal environment within very tight boundaries. 

Define physiology.

Branch of biology that deals with the normal functions of living organisms and their parts; the way in which a living organism or bodily part functions.  

Physiology reflects much of conscious perception of internal and external world.  

External: changes in temperature, or senses. 

Internal: increases in heart & breathing rate during exercise, or pounding of heart when scared.  

Define homeostasis.

The maintenance of the internal environment within very tight boundaries. 

Describe homeostasis

Negative feedback mechanism. System monitored by sensory detector, disturbance from set point, change detected by sensory detector, action triggered to counteract change and restore to set point. 

Describe what happens if body temperature differs from set point.

Core temperature in body maintained at around 37 °C (alters slightly following circadian rhythm). Body temperature decreases: add clothes (behavioural), vasoconstriction – decrease blood flow to skin, shiver – increase respiration, more heat (physiological). Body temperature increases: remove clothes (behavioural), vasodilation – increase blood flow to skin for heat to transfer off, sweat – more heat transfers off (physiological). 

What happens if body temperature increases too high?

Too hot (body temp above 41 °C) tertiary structures of proteins denature, leaving them unable to function, above 40 °C considered medical emergency.

What happens to body temperature when infected with bacteria or virus?

Hypothalamus monitors core body temperature. Temperature receptors in skin send sensory inputs to neurones within hypothalamus. Neurons within preoptic nucleus of hypothalamus respond directly to change in temperature.  

When infected with bacteria or virus, fever may occur. Fever causes resetting of thermal set point (increases core temperature) in preoptic area of hypothalamus by pyrogens. Pyrogens most commonly come from chemicals in cell walls of bacteria, and from prostaglandins in walls of neutrophils, macrophages & lymphocytes.

Why is fever beneficial? And what may help to reduce fever?

Benefits of fever: reduce rate of replication of some microbes - limits development of infection. Enhance generation of specific lymphocytes that strengthen immune response.

‘Anti-pyretic’ drugs reduce fevers.

Ibuprofen (& other NSAIDs), paracetamol and aspirin.  

NSAIDs & paracetamol work by inhibiting enzyme cyclooxygenase, which prevents prostaglandin production.  

What are different homeostatic variables?

Regulated variables – directly controlled/regulated and contain specific sensors which monitor change. Body temperature monitored by peripheral & central temperature receptors.  

Unregulated variables: contribute to control process but do not have specific sensors. Rate of breathing during exercise – breathing rate increases (unregulated variable) because of carbon dioxide levels rising (regulated variable, monitored by chemoreceptors). Unregulated variable plays important part in control of regulated variable.  

Describe a positive feedback system.

Positive feedback systems – change in on parameter gives rise to further change and causes change to progressively increase. Rare as cause a ‘run-away’ phenomenon.  

MUST have a clear end point. Childbirth – increase of nervous impulse and the maintenance of uterine contractions, end point reached when baby arrives, system switched off, homeostasis restored.  

Describe what the plasma membrane does for a cell.

Plasma membrane encloses the cell, regulates cell function by: controlling what substances enter or leave the cell, controlling communication between the cell and the rest of the body (interaction of hormones/nervous impulses). 

Plasma membrane allows cell to maintain different composition of internal cytoplasm compared to extracellular fluid. Membrane is readily permeable to few substances, either impermeable or shows regulated permeability to other substances.  

Describe the strucutre of the plasma membrane.

phospholipids and proteins. Phospholipids have hydrophilic heads and 2 hydrophobic tails, in aqueous solution the heads face outwards, and the tails gather in two rows to form a bilayer arrangement. Hydrophobic core of lipid bilayer makes the bilayer impermeable to most water soluble, polar molecules and to charged ions like Na+. Bilayer impermeable to large molecules (i.e. amino acids). Permeable to small polar molecules such as O2, CO2 and water, and fat-soluble substances like steroid hormones.

What are the two types of membrane proteins?

Extrinsic proteins – do not pass all the way through membrane, can sit on inner or outer facing side. These may make up the cytoskeleton, membrane – bound enzymes and G-proteins. Interact with either other cytoskeleton proteins or with polar heads of lipids.  

Integral (intrinsic) proteins – embedded in bilayer and may span width of membrane, so are exposed on both intracellular & extracellular surfaces. Perform number of different roles: provide means of transport across membrane (membrane pores), transport of many substances which cannot pass though lipid bilayer because they are too large or are polar molecules.  

Describe passive & active transport.

Passive – only occurs where differences in the concentration or electrical gradients occur across the membrane, this causes a reduction in these gradients (e.g. equalisation of concentration of the substance either side of the membrane).  

Active – requires expenditure of energy to move substances across membrane.  

Define diffusion.

Diffusion – passive process by which molecules move from a region of high concentration to a region of lower concentration down a concentration gradient. End point achieved when molecules evenly distributed. Molecules move due to Brownian motion – random movement of particles suspended in a liquid or gas. Particles constantly colliding with other molecules that are continually moving. Energy of movement increases with temperature. 

What characteristics/properties are associated with the head and tails of phospholipids?

Hydrophilic head and hydrophobic tails

Give an example using oxygen for diffusion.

If a cell is metabolizing and using O2 then the O2 concentrations within the cell will be lower than those in the adjacent capillaries, so O2 will tend to diffuse into the cell, down its concentration gradient, thereby supplying the metabolic needs of the cell. At the same time, the metabolic activity will lead to the production of CO2 inside the cell, such that the concentration of CO2 is higher inside the cell compared with outside, thus the CO2 will tend to move out of the cell, down its concentration gradient.

What factors affect the rate of diffusion?

Temperature - affects the kinetic energy of the molecules; the higher the temperature the higher the kinetic energy. Temperature well regulated in body so unlikely to be significant changes.

Density - higher density or viscosity the slower the rate of diffusion as greater frequency of collisions between particles and medium diffusing through.

Molecular/particle size - greater the size the greater the frequency of collisions between the particles and medium so slower rate.

Concentration gradient - greater the difference in concentration between two regions the more rapid the rate of diffusion is, as moves towards equilibrium this rate slows down.

What is the equation related to the rate of diffusion? Label what each part means and give the units.

J = -DA(Δc/x)

J = the rate of diffusion in molecules per unit time crossing the membrane, mol m−2 s−1​

D = the diffusion coefficient, m2 s−1​

A = the area of the membrane, m2​

Δc = the concentration gradient across the membrane, the difference in the numbers of particles, m−4​

x = the thickness of the membrane, m.​​

The diffusion coefficient (D) in Graham’s and Fick’s laws of diffusion is a characteristic of what? (Please select all that apply.)

A - The substance that is diffusing​

B - The medium that diffusion is occurring in​

C - Temperature​

D - The cross-sectional area over which the substance is diffusing

A, B & C

D is a distinct parameter.

Describe osmosis.

Diffusion solely focused on the movement of water. Water diffuses from an area where solute is relatively dilute to area where it is more concentrated.  

Example: 2 solutions different concentrations of NaCl either side of plasma membrane, sodium and chloride ions cannot pass through the membrane as it is impermeable to ions. Water will flow from the dilute (hypotonic) solution to the more concentrated (hypertonic). Same as diffusion as water is moving from region of high concentration to region of lower concentration. Flow of water across cell membrane plays important part in the regulation of cell volume.  

What are aquaporins?

Aquaporins widely distributed across cell membrane and exclusively regulate the movement of water across the membrane. Specific role in regulating water balance in body via key structures such as collecting ducts in kidneys.  

Describe the different kinds of passive protein mediated transport.

Involves integral proteins, proteins take on role of channels and carrier proteins. 

Channels – protein structures which create a pore which spans the membrane – this makes substance being transported separate from the phospholipid bilayer. Channels selective to substances they allow through based on size & charge of molecule.  

Potassium leakage channel – 4 subunits which form a pore, selectivity filter on extracellular surface of channel & filter ions based on charge and size so thar only K+ ions can pass through. Channel always open, leaks through continuously. Plays key role in maintenance of resting potential of neurones.  

Gated channels – open or closed, nothing in between. Less control as a result. At rest are usually closed but can be opened – e.g. change in electrical gradient across membrane which causes small change in tertiary structure of protein so channel can be opened. Voltage gated channels. Na+ VG channels integral to generating action potential. 

What are carrier proteins? Describe how they work.

Carrier proteins – substances pass through membrane with proteins forming channel. Substance binds to site on surface of protein, binding process leads to conformational change of shape to protein, results in transport of substance across the membrane. Usually highly specific to substance being transported. Because transport depends on binding, process shows same kinetics as enzyme mediated reactions. Number of carriers can limit rate of transport – carriers become saturated; rate of transport can no longer increase past this point irrespective of concentration of substance.  

Example – re-absorption of glucose in tubules of kidneys. Blood glucose level rises too high, glucose carrier proteins saturated so glucose appears in urine as not absorbed.  

Describe the mechanism of primary active transport.

Na+K+ATPase pump: 

1. Three Na+ & 1 ATP bind to membrane – spanning protein. 

2. ATP phosphorylates the pump protein, releasing ADP. 

3. Phosphorylation of pump protein leads to conformational change – releases 3Na+ ions into extracellular space & allows 2 K+ ions to bid.  

4. Pump protein dephosphorylates, reverting to original shape and releases 2 K+ ions into intracellular space.  

What is secondary active transport?

Na+ gradients provide source of potential energy which can be used to drive other processes - termed secondary active transport.

Cotransport (or symport) – substance being transported moves in same direction as Na+. Example: absorption of glucose (& some amino acids) by small intestine: epithelial cells lining small intestine have Na+K+ATPase pumps on basolateral membranes (membranes located sides and base of cells, away from lumen of intestine) which pump Na+ out of cells into extracellular fluid. Pumping maintains low concentration of Na within cells. Apical membrane (portion of cell membrane that faces lumen of organ – characterised by presence of microvilli) have carrier proteins that cotransport sodium and glucose, driven by movement of Na+ down concentration gradient into the cell.  

Exchange (or antiport) – substance moves in opposite direction of Na+ ions. Example: movement of calcium out of the cell in exchange for sodium, as occurs in cardiac muscles (electrochemical signalling – single Ca2+ exported for import of 3Na+, results in depolarisation). 

What happens to glucose absorption if metabolic activity in cells stopped? 

Carrier proteins do not directly use the metabolic energy provided by the Na+K+ATPase pump, but only function in presence of the Na+ gradient created by Na+K+ATPase pump on the basolateral membrane - hence term secondary active transport. In absence of metabolic activity, sodium gradient would decline, and the intestine would no longer be able to absorb glucose.  

Describe endocytosis.

Endocytosis – transport into cell of substances in membrane – bound vesicles. Transports substances through which cannot normally pass through into cell. Substance is engulfed by invagination of membrane, creates a vesicle, internalised within cell.  

Phagocytosis – the immune response, process where macrophages (and similar cells) engulf and break down pathogens. 

Pinocytosis – fluids containing solutes may be taken into cells, e.g. in small intestine to absorb fat droplets.  

Receptor-mediated endocytosis – substance binds to receptors on surface of cell, receptors located in pits in surface of membrane, these are coated in clathrin so named coated pits. Substance binds to receptor which triggers formation of clathrin – coated vesicle of membrane which is then internalised within the cell.  

Example – recycling of membrane – bound receptors: membrane tagged with ubiquitin, clathrin – coated vesicle of membrane forms allowing receptor protein to be internalised into cytoplasm of cell, then transported to lysosomes for recycling.  

Describe exocytosis.

Transported out of cell as reverse process of endocytosis. Vesicles assembled within cell containing substance, vesicles assimilate into membrane and release substance into the extracellular space. Exocytosis is the mechanisms by how neurotransmitters are released from nerve terminals and secretory proteins (e.g. enzymes) can be released (e.g. digestive enzymes into intestine). 

Give a clinical example for malfunctioning of a transport system.

Malfunctioning of transport system – genetic mutation affecting channel proteins.  

Characterised by production of very thick, viscous mucus which blocks narrower air ways in the lungs, affects pancreatic function (blocks ducts – prevents digestive enzymes reaching small intestine, blockage leads to exocrine pancreatic insufficiency which impairs body from digesting fats, proteins & carbohydrates, causes nutritional deficiencies), blocks intestines from thick mucus.  

Respiratory difficulty particularly prominent as airways blocked from mucus and repeated bacterial respiratory tract infections.  

Inherited disorder, mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR). Autosomal – recessive disease, both parents must carry defective gene for offspring to be homozygous and be affected by disease. All babies tested few days after birth by heel prick test.  

Impacts on lung function:  

Healthy lungs – airways lined with fluid – airway surface liquid (ASL). Layer of mucus sits on top of this, purpose is to trap bacteria and particles which enter respiratory system. Cilia which line airways sweep the mucus and its contents up away from the lungs. 

CF lungs – CTFR mutation causes changes in channel proteins of epithelial cells of the airways, affects movement of chloride ions out of the cell. Also leads to failure of regulation of the epithelial sodium channel (EnaC). Increases sodium reabsorption from the airways. In turn causes more water to be drawn from the mucus layer into the cell with the sodium. Causes much thicker, more viscous mucus. 

No cure currently, treatments are towards limiting effects of the disease: e.g. physiotherapy to help move mucus & clear airways, drug treatments to reduce viscosity of mucus – makes it easier to clear airways. Recent developments include drugs that enhance opening of chloride channels, beneficial in patients with mutation that affects rate of production of channel proteins.