Intracellular Compartments And Trafficking

Question 1

What’s important in intracellular compartments?

Answer 1

It is essential that correct amounts of fluids at correct concentrations are maintained in the different compartments for all biochemical reactions to take place.

Question 2

Substances require water to diffuse through:

Answer 2

> Short distance diffuse through water.

> Longer distance diffuse through the blood.

Question 3

Total body water

Answer 3

60% changes with age and weight

Question 4

2 main compartments are

Answer 4

Extracellular and Intracellular fluid compartments. ECF and ICF respectively
> ICF= 2/3 of Total body water
>ICF = 1/3 of Total body water
e.g a 75kg person, has 45 kg of water [60% of total body weight/water kilos same as litres] ICF is 2/3 of that 60% so ICF= 30 kg AND ECF is 1/3 of that 60% so ECF is = 15 kg.

Question 5

Transcellular compartment contains

Answer 5

synovial, peritoneal, pericardial, and cerebrospinal fluids.

Question 6

Intracellular fluid compartment -ICF

Answer 6

> Found inside 100 trillion cells of the body
Concentration of substances within cells is very similar from cell to cell, therefore the ICF is considered as one large fluid compartment.

Question 7

Extracellular fluid compartment - ECF

Answer 7

> Is ALL fluid outside of cells.
Divided into 2: Interstitial fluid (ISF) and Plasma
ISF = 3/4 of ECF and 15% of Total body water
Interstitial fluid surrounds the cells but is outside of the blood vessels. it contains very litte protein and few cells in suspension.

Question 8

Blood Plasma definition and function.

Answer 8

> It is the fluid inside blood vessels.
It carries components of blood i.e red blood cells and white blood cells and plasma proteins.

Blood plasma forms 1/4 of ECF or 5% of total body water.

Question 9

Fluid movements

Answer 9

• Movement of water is determined by hydrostatic pressure and osmotic pressure
• Hydrostatic pressure from pumping action of the heart
• Osmotic pressure by concentration of solute particles
• Water moves from dilute to concentrated solutions. [from high concentration of water to low concentration of water.][from low concentration of solutes to where there is high concentration of solutes]. Such that the more solutes there are the greater the pull on the water molecules

Question 10

Osmolarity is determined by

Answer 10

• the number of osmotically active particles per litre. Normal body fluid osmolarity is 282 mOsm/L –read up on osmolarity and osmotic pressure and osmotic equilibrium in Guyton pp289-301 very impt!
• Osmolarity is the concentration of a solution expressed as the total number of solute particles per litre.

Question 11

Osmotic pressure

Answer 11

is the minimumpressurewhich needs to be applied to asolutionto prevent the inward flow of its puresolventacross asemipermeable membrane

Question 12

osmotic equilibrium

Answer 12

is a point at which theosmoticpressure of the solutions on each side of the membrane becomes equal. At this point, the net transfer of water across the membrane is zero.

Question 13

Fluid Intake and Output

Answer 13

Amount of water needed varies – climate and activity • Water intake via foods and 10% by metabolism • Water is lost via urine, faeces and sweat, and evaporation via lungs and skin –also varies based on climate and activity • About 300mL of urine needs to be produced to rid body of nitrogenous wastes • Fluid intake is controlled by sensation of thirst –stimulated by increase in osmolarity sensed by hypothalamus in brain or a fall in blood volume • Immediate cessation of thirst occurs after drinking to prevent excessive consumption –this encourages small frequent drinks of water until fluid balance is restored • Salty food stimulate thirst – salty popcorn

Question 14

Water loss in kidneys

Answer 14

> Kidneys filter the plasma to form urine • Hydrostatic pressure of blood drives the process – and blood flow to kidneys • If blood volume is low then less filtrate is formed and if blood volume is high then more filtrate is produced • Large volumes of filtrate is produced - 120ml/min ~to170 L/day • Large amount of water recovered in the tubules by transport processes and urine passes into collecting ducts into the bladder

Question 15

Vasopressin [causes water retention when the body needs it]

Answer 15

> Volume of urine is controlled by hormone vasopressin
• Aka antidiuretic hormone (ADH) released from posterior pituitary
• Stimulated by osmoreceptors in hypothalamus in response to osmolarity of blood
• Also secreted in response to fall in blood pressure –sensed by pressure receptors in heart and large blood vessels
• 75% of water recovered by osmosis in proximal tubules
• Final urine concentration determined by latter part of tubules
– When urine needs to be concentrated vasopressin released and acts on cells in distal tubule and collecting ducts to increase permeability to water
– Tissue surrounding ducts is hyperosmotic compared to dilute urine therefore urine passes back into tissue and blood
– No vasopressin release in high blood pressure or hypo-osmotic blood –dilute urine produced

Question 16

Dehydration

Answer 16

> If water intake does not cover water losses dehydration occurs • Water moves out of cells into isf and cells shrink – Dry mouth, thirst, dry skin and low volume of urine leading to weight loss, fever and confusion – Concentration of blood also increases workload of heart and leads to increased blood viscosity which may lead to blood clots.

Question 17

Excess urine production in diabetes

Answer 17

> In diabetes mellitus excess sugar in urine increases the osmolarity of urine and prevents water reabsorption
In diabetes insipidus < more than 40 L urine /day produced due to failure of vasopressin release or failure of kidney to respond to vasopressin, therefore more urine is produced.

Question 18

Oedema

Answer 18

> Swelling of tissues due to accumulation of fluid is called oedema
• Has many different causes
• Large quantities of fluid exchanged between compartments

• Hydrostatic pressure favours fluid leaving blood vessels over colloid osmotic pressure [colloid osmotic pressure = In thecapillarieshydrostatic pressureincreases filtration by pushing fluid and solute OUT of the capillaries, while capillaryoncotic pressure(also known ascolloid osmotic pressure) pulls fluid into the capillaries and/or prevents fluid from leaving.] so, when oedema occurs, Hydrostatic pressure moves more fluid out of the vessel than colloid osmotic pressure can bring in. so we end with more fluid in the interstitial fluid resulting in oedema.

• Although fluid is returned to the circulation under normal circumstances if there is a small amount retained by the tissues oedema occurs
• Eg feet after a long day in shoes that fit

Question 19

Compartmentalization allows for

Answer 19

• greater size, complexity and efficiency but creates a problem, How do you communicate between the cellular compartments???? [How does stuff within the cell communicate with each other, since everyone is membrane bound?]

Answer to that is: Vesicular Transport!

Question 20

Vesicular Transport

Answer 20

• Major part of communication is vesicular transport
• Cargo loaded vesicles [vesicles with stuff= cargo] form at a donor compartment with the help of specific coat and adaptor proteins (COP I and II, clathrin)
• Vesicles then target appropriate acceptor compartment to which they attach by tethers (SNAREs)
• Vesicular transport enables proteins in membrane bound vesicles to move between cell compartments including the outer cell membrane.

Question 21

The TWO major pathway that Vesicular transport occurs

Answer 21

Both pathways mediated by vesicular transport machinery and there is cross-talk between both pathways.

> Shuttles moving material outward or inward

1. Exocytic pathway
2. Endocytic pathway

Question 22

EXOCYTIC PATHWAY

Answer 22

• Proteins synthesized in the cytoplasm translocated into Endoplasmic reticulum (ER)
• Rough ER is where all secreted proteins are made and all proteins resident in compartments connected by vesicular transport
• ER is where most lipids in cells made
• From ER membranous vesicles shuttle cargo to Golgi apparatus
• ER cargo enters via the cis cisterna and moves through the medial and trans cisternae
• In trans cisternae proteins destined for secretion or for incorporation with the PM are packed into secretory vesicles that fuse with the PM [plasma membrane]
• This occurs either constitutively (to replace used or lost membrane) or regulatory, as a response to an external signal
• Golgi is also a major sorting compartment as cargo is also transported to endosomes and lysosomes and back to ER.

Question 23

ENDOCYTIC PATHWAY

Answer 23

• Proteins and membrane are internalised from the environment via endosomes (early and late) to the lysosome
• Membrane receptors internalised via
• Proteins and viruses are internalised by caviolar or raft dependent routes
• Dependent on GTPase dynamin for fission of the forming PM vesicle
• Fluid phase cargo may also enter via a dynamin independent route
• Popular pathway is clathrin coated vesicles through early and late endosomes to lysosomes
• In the first set of endosomes (sorting) cargo is sorted for recycling back to the PM (or Golgi) via recycling endosomes or to the lysosome via late endosomes
• Lysosome is major degradation site for internalised material and cellular membrane proteins

Question 24

Trafficking between the Golgi and endosomes

Answer 24

• Bidirectional movement between Golgi and endosomes, transport from one side of a polarised cell to the other, and secretion of materials from late endosomes
• All proteins/lipids destined for function in any compartment connected by vesicular transport need to be translocated to ER first, there needs to be a pathway to transport newly synthesized endosomal and lysosomal proteins and lipids to endocytic compartments
• These proteins are labelled with mannose6-phosphate (M6P) in the Golgi.
• M6P cargo then sorted by M6P receptors in the trans Golgi into vesicles that are targeted endocytic compartments
• Lower pH in endosomes causes disassociation of the M6P receptor from the cargo and the receptor is recycled back from endosomes back to Golgi

Question 25

Transcytosis

Answer 25

• Polarisied cells such as epithelial cells and neurons contain distinct functional PM domains: apical and basolateral and somatodentritic and axonal, respectively
• Polarised cells use endocytic pathway to shuttle cargo between distinct PM domains
• Cargo is internalised from PM on one side of the cell eg apical side that faces the lumen of organs
• Cargo first delivered to early endosomes can be shuttled via common set of late endosomes and then through basolateral early endosomes to the PM on the basolateral side
• Thus transcytosis can selectively move material through cells across tissue barriers eg epithelium lining the intestines
• Exocytic machinery like tethering complexes and SNAREs are required for this process.

Question 26

Late Endosome to Plasma Membrane

Answer 26

• Transported macromolecules of late endocytic compartment is redirected to the PM and secreted inside small vesicles – exosomes
• Multivesicular bodies (MVBs) are late endosomes that contain internal membrane surrounded cargo.
• Normally fuse with lysosomes but can fuse with PM and secrete exosomes to external environment.
• Important for communication between cells and used for secretion of components into blood stream and signalling.
• Plays a role in spreading of infectious agents e.g HIV can hijack this route to be released from cells.

Question 27

> The ratio of red blood cells to the volume of whole blood is called *** and is usually between 0.36 and 0.53

Answer 27

*** haematocrit.

Question 28

Total blood volume is?

Answer 28

5.5L if a person is 70kg adult. 3.5 L is plasma the rest is red blood cells.

Question 29

All cell compartments are separated by?

Answer 29

semipermeable membranes