IMMS 2: Cells & metabolic processes Flashcards

Metabolic fuels & diet; Glycolysis, Krebs & oxidative phosphorylation; Fatty acid oxidation & ketones; Living control mechanisms; Membrane ultrastructure & transport; Water & sodium

1
Q

What is metabolism?

A

Sum of chemical reactions taking place within each cell.

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2
Q

Name the four main pathways dietary components are metabolised by.

A
  1. Biosynthetic (creating molecules).
  2. Fuel storage.
  3. Oxidative processes (breaking down molecules to make energy).
  4. Waste disposal.
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3
Q

What is a xenobiotic?

A

A substance that has never come from a living thing e.g. chemicals that have been completely synthesised. Needs to be broken down in the body and excreted.

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4
Q

What is an anabolic process?

A

A process where larger molecules are synthesised from smaller components. Used in constructive metabolism e.g. storage of fats.

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5
Q

What is a catabolic process?

A

A process where larger molecules are broken down into smaller components. Used in oxidative and waste disposal processes.

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6
Q

What is daily energy expenditure (DEE)?

A

Total number of calories burned in 24h period, including for physical activity.

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7
Q

How much protein is needed in the diet per day and why?

A

0.8g/kg/day to gain essential amino acids.

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8
Q

What is the most energy dense: protein, lipids, or carbohydrates?

A

Lipids; 9kcal/g
Protein & carbohydrates are only 4kcal/g

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9
Q

How is excess fuel stored for lipids, carbohydrates, and protein?

A

Lipids: adipose tissue (15% water).
Carbohydrates: glycogen in liver and muscle.
Protein: muscle (80% water).

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10
Q

How much does 10ml of alcohol weigh and how many units of alcohol is this?

A

8mg (less dense than water). One unit of alcohol.

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11
Q

What is the basal metabolic rate?

A

Energy needed to stay alive at complete rest (not including digestion).
1kcal/kg/hour average but depends on a variety of factors.

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12
Q

What lowers basal metabolic rate?

A

Lowers with age
Female (higher BMR in males)
Starvation
Hypothyroidism
Decreased muscle mass
Lower BMI

(infection/chronic disease and low ambient temp raise BMR)

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13
Q

How many kcal/g is alcohol?

A

7kcal/g

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14
Q

What happens during an overnight fast?

A

Insulin secretion reduces, glycogen stored in the liver is broken down using glycogenolysis. Glycogen stores depleted down to 80g remaining.

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15
Q

What happens during a fast lasting longer than four days?

A

Change in metabolism, reduction in BMR. Liver creates ketones from fatty acids. Brain adapts to using ketones.

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16
Q

When does gluconeogenesis occur?

A

When glycogen stores have been depleted. Instead need to create glucose from breaking down fat (lipolysis) or protein (proteolysis).

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17
Q

Define malnutrition.

A

Deficiency, excess, or imbalance of energy, protein, or other nutrients, causing adverse effects.

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18
Q

What are the 9 essential amino acids?

A

Histidine
Isoleucine
Leucine
Lysine
Methionine
Phenylalanine
Threonine
Tryptophan
Valine

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19
Q

What is the main function of retinol and can it be stored?

A

Retinol = Vitamin A
Immune system, vision in dim light, skin and other epithelium.
Excess retinol can be stored in the liver.

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20
Q

Name some important B vitamins and can they be stored in the body?

A

Thiamin (B1)
Riboflavin (B2)
Niacin (B3)
Pantothenic acid (B5)
Pyridoxine (B6)
Biotin (B7)
Folate (folacin/B9) and folic acid (manmade folate)
Cobalamin (B12)

Most B vitamins cannot be stored. Folate and B12 can be stored in the liver.

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21
Q

What happens if you take too much pyridoxine?

A

Too much pyridoxine (B6) can cause peripheral neuropathy.

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22
Q

What do cobalamin, folate, and iron have in common?

A

They are needed for making red blood cells. Deficiencies can cause B12/folate/iron deficiency anaemias.

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23
Q

Which vitamin is needed to prevent scurvy?

A

Ascorbic acid/vitamin C.
Needed for healthy skin/bones/cartilage, wound healing.

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24
Q

What is the main function of calciferol?

A

Vitamin D. Regulating the amount of calcium and phosphate in the body.

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25
Q

Why is vitamin E (tocopherol) important?

A

Maintaining healthy skin and eyes, strengthening the immune system.

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26
Q

Which vitamin, stored in the liver, is vital for clotting and wound healing?

A

Vitamin K

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27
Q

What mineral is needed in diet for making thyroid hormones?

A

Iodine

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28
Q

Which vitamins are fat soluble?

A

A, D, E, K

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29
Q

Which vitamins are water soluble?

A

Vitamin C and most of the B vitamins.

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30
Q

What percentage of daily energy should come from free sugars?

A

No more than 5%

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31
Q

What is the maximum amount of saturated fat for women and men?

A

20g for women. 30g for men.

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32
Q

What is the recommended maximum amount of salt per day?

A

2.4g/day of sodium = 6g of salt

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33
Q

What are the guidelines around alcohol intake?

A

No more than 14 units of alcohol per week, spread over at least 3 days, with some alcohol free days.

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34
Q

What are the substrates and intermediates of the Kreb’s Cycle?

A

“Citrate Is Kreb’s Starting Substrate For Making Oxaloacetate”

Starting substrate = acetyl CoA -> Citrate -> Isocitrate -> alpha Ketoglutarate -> Succinyl-coA -> Succinate -> Fumarate -> Malate -> Oxaloacetate

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35
Q

How many enzymatic reactions are in the Kreb’s Cycle?

A

8

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36
Q

Where does the Kreb’s Cycle occur and in what conditions?

A

Mitochondrial matrix under aerobic conditions.

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37
Q

What are the main purposes of the Kreb’s Cycle?

A
  1. Generates energy for the cell.
  2. Provides final common pathway for oxidation of carbohydrates, fats, protein.
  3. Produces intermediates for synthesis of amino acid, glucose, heme etc.
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38
Q

What is the energy gain from the Kreb’s Cycle?

A

6xNADH + 2xFADH2 + 2xGTP

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39
Q

Where does oxidative phosphorylation occur and in what conditions?

A

Inner mitochondrial membranes under aerobic conditions.

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40
Q

Which generates more energy, Kreb’s Cycle or oxidative phosphorylation?

A

Oxidative phosphorylation, around 30 ish ATP per glucose molecule.

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41
Q

What are the two key parts of oxidative phosphorylation?

A

The Electron Transport Chain (ETC) and chemiosmosis.

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42
Q

How is H2O produced in respiration?

A

The final electron acceptor in ETC is oxygen, which picks up the final electrons and hydrogen = H2O.

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43
Q

What is ATP?

A

Adenosine 5’ triphosphate.
Adenine base + ribose + three phosphate groups which are linked with high energy bonds.

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44
Q

What does hydrolysis of ATP result in?

A

Release of energy from breaking bonds between phosphate groups. ATP = ADP + energy.

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45
Q

What is glycolysis?

A

Metabolic pathway which converts glucose by splitting it into two three-carbon molecules called pyruvates. A small amount of ATP is generated.

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46
Q

Where does glycolysis occur and in what conditions?

A

In cytosol (liquid part of cytoplasm), can occur in anaerobic or aerobic conditions.

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47
Q

Why do RBCs use glycolysis?

A

RBCs don’t have mitochondria, which is where Kreb’s and oxidative phosphorylation occurs, so have to use glycolysis.

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48
Q

What are the two stages of glycolysis?

A
  1. Preparative phase (uses 2x ATP).
  2. ATP generating phase (produces 4x ATP, 2x NADH, 2x pyruvate).
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49
Q

Why is the preparative phase in glycolysis important?

A

The preparative phase involves the phosphorylation of glucose, which makes it more polar, “trapping” it in the cell (can’t pass back through membrane), which commits it to the glycolytic pathway.

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50
Q

Why does vigorous exercise lead to lactic acid build up?

A

In aerobic conditions, pyruvate (product of glycolysis) enters mitochondria and is used in Kreb’s cycle.
In anaerobic conditions, pyruvate (catalysed by lactate dehydrogenase) => 2NAD+ and lactic acid as byproduct.
In vigorous exercise, not time to break down lactate in liver, so builds up in tissue.

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51
Q

What is allosteric regulation?

A

An inhibitor or activator binds to a protein (e.g. enzyme) and alters its activity by changing its shape (e.g. activator binds, active site of enzyme becomes compatible with substrate).

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52
Q

What are the key hormones involved in glycolysis?

A

Insulin, glucagon, and catecholamines.

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53
Q

What is the structure of fatty acids?

A

Carboxylic head group with aliphatic tail. This tail is a hydrocarbon chain which can be saturated or unsaturated.

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54
Q

Are fatty acids and lipids the same thing?

A

No, fatty acids are a class of lipids. Examples of other classes of lipids are glycerides (glycerol-containing lipids), non-glycerides (e.g. steroids), and complex lipids (e.g. lipoproteins).

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55
Q

What is a triglyceride?

A

Glycerol molecule bound to three fatty acid molecules. The hydroxyl and carboxyl groups of a glycerol and fatty acid are esterified together to form a triglyceride.

56
Q

What is esterification?

A

Esterification is a chemical reaction that combines an alcohol and an organic acid to produce an ester and water. For example, glycerol + 3xfatty acids = triglyceride + water.

57
Q

What is the structure of a phospholipid?

A

Polar phosphate head and 2x alcohol molecules, and 2x non-polar fatty acid tails.

58
Q

How does the body process ingested fats?

A
  1. Bile salts emulsify fats
  2. Lipases in intestine break down into fatty acids
  3. Intestinal mucosa takes up fatty acids & convert into triglycerides
  4. Triglycerides are combined with cholesterol & apoproteins into chylomicrons
  5. Chylomicrons travel in bloodstream to cells for fuel or storage.
59
Q

How do fatty acids enter the mitochondria?

A

Fatty acids have to be activated in the cytoplasm, using ATP to process into acyl CoA.
acyl CoA can diffuse through the mitochondrial membrane if <12 carbons. If too long (>14 carbons, most dietary fatty acids) they need to be taken through carnitine shuttle.

60
Q

How do fatty acids produce acetyl-CoA?

A

Through fatty acid beta-oxidation cycle. One acetyl-CoA produced each round of cycle.

61
Q

What are ketones?

A

Molecules produced by the liver from acetyl-CoA. Acetone, acetoacetate, and beta-hydoxybutyrate are all ketones.

62
Q

When does fatty acid oxidation occur?

A

When the demand for energy outweighs the amount of glucose available in cells for glycolysis. For example, during exercise, fasting, febrile illness, hypothermia.

63
Q

Why does fatty acid oxidation produce ketones?

A

During high rates of fatty acid oxidation, large amounts of acetyl-CoA are generated, exceeding capacity of krebs cycle. Excess acetyl-CoA is used in ketogenesis.

64
Q

What affects do glucagon and insulin have on ketogenesis?

A

Glucagon activates ketogenesis. Insulin inhibits ketogenesis.

65
Q

Why might an alcoholic have ketoacidosis?

A

If ETOH dependent, likely not to eat a good diet (depleted protein & carbohydrate stores) and most energy source is alcohol. Alcohol directly increases lipolysis.

66
Q

What is homeostasis?

A

The maintenance of a constant internal environment.

66
Q

What is an osmotic gap?

A

Difference between actual serum osmolality and calculation of what the osmolality should be considering levels of sodium, potassium, urea, and glucose. Suggests large quantity of something is in the blood that shouldn’t be e.g. alcohol or ketones.

67
Q

Describe the homeostasis model.

A

Set point (normal range) monitored by control centre, which triggers effector to alter the regulated variable. Sensors test if have returned to set point or if effectors should continue, feed back to the control centre.

68
Q

Explain the difference between autocrine and paracrine communication.

A

Autocrine: cells communicating within themselves.
Paracrine: cells communicating with neighbouring cells via signal diffusing across gap between cells e.g. interleukins between white blood cells.

69
Q

What is endocrine communication?

A

Endocrine: cells communicating with other cells elsewhere in the body via hormones in the bloodstream.

70
Q

What is a hormone?

A

A molecule which acts as a chemical messenger.

71
Q

What are the different types of hormones?

A

Amine, peptide, and steroid hormones.

72
Q

What are the characteristics of amine hormones?

A

Smallest type of hormone and is hydrophilic, adrenaline & noradrenaline are the main amine hormones.

72
Q

What amino acids are amine hormones derived from?

A

Tyrosine and tryptophan.

73
Q

What do peptide and amine hormones have in common?

A

Both produce a quick reaction. Synthesised in advance and stored in vesicles. Dissolve in blood (both are hydrophilic).

74
Q

What is the structure of peptide hormones?

A

Made of amino acids, varying in size from a few amino acids to small proteins. Some have carbohydrate side chains (glycoproteins).

75
Q

What is the structure of steroid hormones?

A

Made of cholesterol which contain fatty acids with hydrophobic carbon chain; don’t dissolve in water but can dissolve in lipids.

76
Q

How are steroid hormones transported to target cells?

A

Released as made, diffuses through membrane, bound to transport protein in blood e.g. albumin. Diffuse through target cell membrane to receptor inside the cell, causes changes in DNA transcription.

77
Q

What type of hormone is most commonly involved in positive feedback loops?

A

Peptide hormones. E.g. oxytocin in labour.

78
Q

What sort of feedback loop does homeostasis use?

A

Negative feedback loops.

79
Q

What are the main roles of microtubules?

A

Give structure to the cell and allow it to change shape e.g. to engulf something.

80
Q

Where are proteins synthesised?

A

Ribosomes studded on surface of rough endoplasmic reticulum.

81
Q

Where are lipids synthesised and what is another function of this organelle?

A

Smooth endoplasmic reticulum. Site of some drug metabolism.

82
Q

What is the function of the golgi body?

A

Further processes and packages proteins and lipids into vesicles for transport. Reads amino acid codes on proteins which indicates where the protein needs to go.

83
Q

Why are membranes and membrane proteins important?

A

Cell signalling, cell polarisation, compartmentalisation - creates ionic gradients for membrane potential.

84
Q

What is the structure of the cell membrane?

A

Phospholipid bilayer with peripheral proteins (loose attachment, electrostatic) and integral proteins (e.g. channel or receptor) with some cholesterol in between fatty acid tails, on both leaflets.

85
Q

What is the structure of integral proteins in cell membranes?

A

Alpha helix in transmembrane region. Hydrophobic amino acids interfacing with the hydrophobic phospholipid tails in membrane.

86
Q

Why is the specific phosphate group in glycerophospholipids in cell membranes important?

A

Specific phosphate groups are used as signals e.g. PS is usually on cystoplasmic leaflet, flips to exoplasmic leaflet (outer membrane) to signal apoptosis is to occur.

87
Q

What are the different phosphate groups used in cell membranes and on which leaflet do they most commonly occur?

A

Serine (PS: generally cytoplasmic)
Choline (PC: neutral - both sides)
Inositol (PI: generally cytoplasmic)
Ethanolamine (PE: neutral - both sides)
Sphingomyelin (SM: generally exoplasmic)

88
Q

What is a term for a molecule with both hydrophobic and hydrophilic parts?

A

Amphipathic molecule.

89
Q

What is the structure of glycerophospholipids?

A

Phosphate head, glycerol backbone, and two fatty acid tails.

90
Q

What happens to cell membranes in hypothermia?

A

Membranes are temperature sensitive. Hypothermia causes large scale change in properties leading to dysfunction. E.g. less fluid, loss of ionic integrity.

91
Q

Membranes are freely permeable to:

A

Water via aquaporins. Gases e.g. O2. Small uncharged polar molecules e.g. ethanol, urea.

92
Q

Membranes are impermeable to:

A

Ions e.g. K+. Charged polar molecules e.g. ATP. Large uncharged polar molecules e.g. glucose.

93
Q

What affects phospholipid bilayer fluidity?

A

If fatty acids are saturated/unsaturated (C=C bonds). Presence/amount of cholesterol. Temperature.

94
Q

What forces drive membrane transport and basis of membrane potential?

A

Chemical driving force (ion diffusion gradients) and electrical driving force (ions carry a charge).

95
Q

In normal conditions, what is the differences between intracellular levels of K+, Na+, and Cl- to extracellular levels?

A

Intracellular has higher K+ levels and lower Cl- and Na+ levels than extracellular.

96
Q

What are the three main types of membrane protein transporters?

A

Uniport (single substance)
Antiport (two substances in opposite directions)
Symport (two or more substances in same direction)

97
Q

How does water move across cell membranes?

A

Simple diffusion via aquaporins - protein channels across the membrane. Not facilitated diffusion because water doesn’t bind to a protein.

98
Q

How is glucose transported across cell membranes?

A

Facilitated diffusion using carrier proteins.

99
Q

What needs primary active transport to move across cell membranes and why?

A

Ions can need to be moved against gradient, using ATP. Water soluble vitamins also use primary active transport.

100
Q

Where does secondary active transport occur?

A

Mitochondrial membrane to produce ATP. Another example is in renal tubules.

101
Q

What are GPCRs?

A

G-Protein Coupled Receptors. Integral proteins, large family of cell membrane receptors used in cell signalling. >50% of all drugs mimic or inhibit various GPCRs.

102
Q

What is the term for cell membranes of epithelia which face outwards e.g. into intestine?

A

Apical membranes.

103
Q

What is a basolateral membrane?

A

Cell membrane at the base of epithelia next to other cells of the tissue.

104
Q

What is a desmosome?

A

Intracellular junction providing strong adhesion between cells. Particularly important in epithelia.

105
Q

What is the difference between paracellular and transcellular routes?

A

Paracellular is absorption of substances across epithelium by diffusion across intracellular space, controlled by tight junctions (protein complexes).
Transcellular is absorption of substances through cells by active transport or diffusion.

106
Q

What is osmotic drag?

A

Ionic movement causes water to move across with ions via osmosis.

107
Q

Give an example of fenestrated epithelium.

A

Epithelium of glomerulus.

108
Q

Which has an overall negative charge, intracellular cytoplasm or extracellular fluid?

A

Intracellular cytoplasm.

109
Q

What is the name of the equation used to calculate diffusion potential?

A

Nernst Equation.

110
Q

How many litres of water in an average 70kg male?

A

60% of body weight = 42L

111
Q

Where is most of the water in the body stored?

A

Intracellularly: 40% of body weight. 28L in 70kg male.

112
Q

Which extracellular fluid has more water volume, intravascular or interstitial?

A

Interstitial: 11L in 70kg male.
Intravascular only has 3L (and this includes lymph).

113
Q

Is plasma hypertonic, isotonic, or hypotonic, and what does this mean?

A

Isotonic. Means that there is no net flow of water. Solute concentration in plasma is same as inside cells and the solutes cannot cross the cell membrane.

114
Q

What are the main osmotic components of extracellular fluid?

A

Sodium (cation), chloride & bicarbonate (anions), glucose, urea, and proteins e.g. albumin for colloid osmotic pressure.

115
Q

What is the predominant cation in intracellular fluid?

A

Potassium.

116
Q

In normal conditions, what is the difference between intracellular and extracellular osmolality?

A

Zero! Should be equal, osmosis of water across cell membrane should keep osmolality balanced.

117
Q

What does water for injection do to cells?

A

It is hypo-osmolar and hypotonic to cells, so moves into intracellular fluid of RBCs causing haemolysis. Only occurs in vicinity of cannula.

118
Q

What does an increase in extracellular osmolality, e.g. in dehydration, cause?

A
  1. movement of water from intracellular fluid to extracellular.
  2. stimulation of thirst in hypothalamus to increase water intake.
  3. release of ADH from posterior pituitary to increase renal water retention.
119
Q

Which change in extracellular fluid causes a faster homeostatic response: volume or osmolality?

A

Change in osmolality triggers a quicker response.

120
Q

What system maintains homeostasis of extracellular volume?

A

Renin-angiotensin-aldosterone system.

121
Q

What does a raised haematocrit suggest?

A

Haematocrit is proportion of RBCs in blood, raised means not as much water in blood, so RBCs are more concentrated.

122
Q

What processes does reduced extracellular fluid osmolality (water excess) trigger?

A
  1. movement of water into intracellular fluid.
  2. inhibition of ADH from posterior pituitary, causing increased urine volume.
  3. no stimulation of thirst centre in hypothalamus.
123
Q

What are the risks of water intoxication?

A

Hyponatraemia, cerebral overhydration -> headache, confusion, convulsions.

124
Q

What causes reabsorption: capillary hydrostatic or oncotic pressure?

A

Oncotic pressure (difference in protein concentration between plasma and interstitial fluid).
Hydrostatic pressure causes filtration, where water moves into interstitial fluid from plasma.

125
Q

What happens to excess water in interstitial fluid which is not reabsorbed into plasma or diffused into cells?

A

Enters lymphatic system.

126
Q

What is oedema?

A

Excess accumulation of fluid in interstitial space. Caused by disruption of filtration and osmotic forces:
Hypoalbuminaemia.
Obstruction/issue of venous/lymphatic return.
Inflammation (which increases capillary permeability).

127
Q

What type of oedema typically causes swelling of ankles?

A

Venous oedema.

128
Q

What is the difference between exudate and transudate?

A

Transudate is fluid pushed through capillary by high pressure into interstitial space. For example left ventricular failure, pressure increases in capillaries in pleura in lungs, causes pleural effusion (fluid in pleural cavity).
Exudate is caused by capillaries becoming more permeable (e.g. due to infection), allowing fluid including proteins to leak out.

129
Q

Which enzyme catalyses the rate-limiting step of the Krebs’ cycle?

A

Isocitrate dehydrogenase.

130
Q

What enzyme catalyses the rate-limiting step in aerobic glycolysis?

A

PFK1 (phosphofructokinase)

131
Q

Ketones are synthesised from which molecule?

A

Acetyl-CoA

132
Q

By what mode of transport does glucose move into cells?

A

Facilitated diffusion.

133
Q
A