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Flashcards in Physiology. Deck (703):
1

What is the digestive tract?

series of hollow organs, separated by sphincters to control movement.

2

What is the function of the mouth and oropharynx?

to chop and lubricate food and to start carb and fat digestion.

3

What is the function of the oesophagus?

delivery of food to the stomach.

4

What is the function of the stomach?

temporary food storage, continuation of carb and fat digestion, initiates protein digestion. regulates the delivery of chyme to the small intestines.

5

What is the function of the small intestine?

Principal site of digestion and absorption of nutrients.

6

What is the function of the large intestine?

reabsorbs fluid and electrolytes and stores fecal matter, before regulating expulsion.

7

What are the accessory structures of the Gi tract?

salivary glands, pancreas, liver and gall bladder.

8

What does aboral mean?

anal.

9

What are the four main digestive processes?

Motility, secretion, digestion and absorption.

10

What is GI motility?

Mechanical activity mostly involving: propulsive movements, churning movements and tonic contractions.

11

What is GI secretion?

digestive secretions go into the tract in response to hormonal and neural signs.

12

What is GI digestion?

biochemical breakdown of complex food stuffs to smaller absorbable units.

13

What is GI absorption?

transfer of the absorbable products of digestion from the digestive tract to the blood or lymph.

14

What do digestive secretions contain?

water (large volumes extracted from plasma), electrolytes and organic compounds e.g. enzymes, bile salts and mucus.

15

What is the basic principle of fat digestion?

mostly triglyderides converted to monoglycerides and free fatty acids. Mediated by lipases.

16

What is the basic principle of carbohydrate digestion?

Mostly poly and di-, converted to monosaccharides. Mediated by anylases and disaccharidases.

17

What is the basic principle of protein digestion?

protein broken down to amino acids, dipeptides and tripeptides. Mediated by proteases and dipeptidases.

18

Name the layers of the digestive tract starting from the outside and working in?

serosa, longitudinal muscle, myenteric plexus, circular muscle, submucosa, submucosal plexus, muscularis mucosae, mucosa and mesentery.

19

What comprises the digestive mucosa?

epithelial cells (absorption), exocrine cells (enzymes), endocrine gland cells (hormones), lamina proporia (capillaries, neurones and immune cells) and muscularis mucosa.

20

What comprises the digestive submucosa?

connective tissue, larger blood and lymph vessels and the submucous nerve plexus.

21

What comprises the digestive muscularis extrema?

circular muscle layer, nerve network - myenteric plexus and longitudinal muscle layer.

22

What comprises the digestive serosa?

connective tissue.

23

Where is the skeletal muscle in the GI tract?

mouth, pharynx, upper oesophagus and the external anal sphincter.

24

What are the three layers of smooth muscle in the GI tract and what do they do?

circular - lumen becomes narrower and longer.
Longitudinal - intestine becomes shorter and fatter.
Muscularis mucosae - changes the absorptive and secretory area of the smooth muscle.

25

What connects smooth muscle cells to each other?

Gap junctions.

26

What allows electrical currents to move between smooth muscle cells?

the gap junctions for a junctional synctium to allow hundreds of cells to contract and depolarise at the same time.

27

Describe the electrical activity of the stomach and large and small intestines.

spontaneous electrical activity occurs in slow waves via gap junctions, causing rhythmic contraction.

28

How is spontaneous activity modulated in the GI tract?

Intrinsic (enteric) and extrinsic (autonomic) nerves and also numerous hormones.

29

Describe slow wave electrical activity.

it determines the max frequency, direction and velocity of rhythmic contractions. Slow waves are driven by ICC's (interstitial cells of cajal). Contraction only occurs if the slow wave amplitude is sufficient to trigger an action potential. The force is related to the number of action potentials discharged.

30

What are the pacemaker cells of the GI tract?

The interstitial cells of cajal.

31

What channels is the slow wave mediated by?

Upstroke of the wave is Ca channels and the downstroke is K channels.

32

Where are ICC's found?

between the longitudinal and circular muscle layers and in the submucosa. They form gap junctions with each other and the smooth muscle cells.

33

What is the GI basic electrical rhythm?

The electrical rhythm that flows through the tissues, determined by the slow wave. It varies along the length of the GI tract as not all slow waves will trigger a contraction.

34

What determines whether the slow waves will reach the amplitude required to cause contraction?

neuronal stimuli, hormonal and mechanical stimuli etc.

35

What are the BER frequency's of the different part of the GI tract?

stomach - 3 slow per minute.
Duodenum 1-12 waves per min. Tends to drive food in the aboral direction.
Terminal ileum - 8 waves per min.
Proximal colon 8 waves and distal = 16 waves per min. Favours retention of luminal contents facilitating absorption of water and electrolytes.

36

What is the enteric nervous system?

little brain of the gut. cell bodies are found in ganglia largely within the myenteric (Auerbachs) and submucous (Meissner's) plexus. Ganglia are connected by interganglionic fibre tracts. It is located solely in the GI tissues (intrinsic). It forms a closed reflex circuit that can perform independently of the rest of the nervous system. But is strongly modulated by hormones and extrinsic nerve output.

37

What neurones comprise the enteric nervous system?

sensory - mechanoreceptors, chemoreceptors and thermoreceptors.
Interneurones (in the majority) co-ordinate reflexes and motor programs.
Effector neurones - excitory and inhibitory - supplying the smooth muscle, epithelium, endocrine cells and blood vessels.

38

What is the role of parasympathetic innervation of the GI tract?

preganglionic fibres synapse with the ganglion cells within the ENS.
excitory influences - increase pancreatic, gastric and small intestine secretion, increase blood flow and smooth muscle contraction.
Inhibitory - relaxation of some sphincters, receptive relaxation of the stomach.

39

What is the role of the sympathetic innervation of the GI tract?

Postganglionic fibres releasing NA innervate mainly enteric neurones but also other structures. Functionally less important than the parasympathetic division.
Inhibitory - decreased mobility, secretion and blood flow.

40

Describe local long and short reflexes on motor and secretory control in the GI system.

Local sensory, interneurone and effector neurone are all in the myenteric plexus.
Short - sensory neurone goes to the prevertebral ganglion, the interneurone goes back to the myenteric plexus and the effecor neurone goes back to the tissue.
Long is the same but goes all the way to the medulla oblongata.

41

Give an example of local, long and short reflexes.

Local = peristalsis.
Short - intestino-intestinal inhibitory reflex.
Long - gastroileal reflex.

42

Describe peristalsis.

distension of the gut wall activates sensory neurones. This alters the activity of inerneurones, which alter the activity of motoneurones. Longitudinal smooth muscle relaxes behind and contracts in front. Circular muscle contracts behind and relaxes in front.

43

What are the segments in front of and behind a bolus in the intestine called?

The propulsive segment is behind and the receiving segment in front.

44

What is segmentation and how does it occur?

Mixing or churning movements. Rhythmic contractions of the circular muscle mix and divide luminal contents, occurs in the small intestine in the fed state and in the large intestine.

45

What is segmentation in the large intestine called?

Haustration.

46

What are tonic contractions in the GI tract?

sustained contractions found in the sphincters of the tract.

47

Describe the sphincters of the GI tract (excluding the sphincter of oddi).

6 in total. composed of specialised circular mostly smooth muscle. Act as one way valves maintaining a resting positive pressure between the sections. Stimuli usually cause opening and closing.

48

Which sphincters in the GI tract are skeletal muscle?

Upper oesophageal sphincter and the anal sphincter.

49

What does the upper oesophageal sphincter do?

relaxes to allow swallowing and closes during inspiration.

50

What regulates internal (smooth) and external (skeletal) sphincters?

The defecation reflex.

51

What reflexes mediate mastication?

the masseteris and diagastric reflexes.

52

What are the two stages of deglutition? How long do the stages last?

the oropharyngeal (1 second) and the oesophageal (4-10 seconds).

53

Describe the oropharangeal stage of swallowing.

bolus formed in the mouth, the tongue voluntarily forces the bolus into the pharynx. Pressure stimulates the pharyngeal pressure receptors. an involunatary afferent impulse is sent to the swallowing centre in the medulla. efferents initiate an all or nithing reflex sequence of muscle movements. Upper oesophageal sphincter opens and food passes into the oesophagus.

54

Describe the oesophageal stage of swallowing.

medulla oblongata triggers primary peristaltic wave and closure of upper sphincter. peristalsis is controlled by the eneteric nervous system. fibres squeeze the bolus down. Longitudinal fibres in fron shorten the distance. Lower sphincter opens 2-3 seconds before and closes straight after to prevent reflux. If there is sticky food a more forceful second wave is made and increased saliva production is triggered.

55

What is another name for the myenteric plexus?

Auerbachs plexus.

56

What are the 6 main sphincters in the GI tract?

Upper oesophageal.
Lower oesophageal.
Pyloric.
Illeocecal.
Internal and external anal sphincter.

57

What size is the small intestine?

6m long and 3.5cm wide.

58

What are the three parts of the small intestine and what lengths are they?

Duodenum - 25cm
Jejunum - 2.5m
Ileum - 3m.

59

Where does the small intestine receive different fluids from?

Chyme from stomach.
Pancreatic juice from pancreas.
Bile from the gallbladder.

60

What 6 secretions come from the small intestine?

Gastrin, cholecystokinin, secretin, motilin, glucose dependent insulinotropic peptide and glucagon like peptide.

61

where is gastric secreted?

From G cells in the gastric antrum (mainly) and duodenum.

62

where is cholecystokinin (CCK) secreted?

From I cells of the duodenum and the jejunum.

63

where is secretin secreted?

From S cells in the duodenum.

64

where is motilin secreted?

From M cells in the duodenum and jejunum.

65

where is glucose dependent insulinotropic peptide (GIP) secreted?

Is an incretion from K cells of the duodenum and the jejunum.

66

where is glucagon like peptide 1 (GLP-1) secreted?

Is an incretion from L cells of the small and large intestine.

67

What type of receptors do all intestinal secretions act on?

G-protein coupled receptors.

68

What potentiates GIP?

Gliptins e.g. Sitagliptin used in treatment of type two DM.

69

What mimics the activity of GLP-1? And what potentiates the activity?

Potentiated by Gliptins e.g. Sitagliptin used in treatment of type two DM.
Mimicked by extenatide also used for treatment of DM type 2.

70

What is the juice of the intestine called?

Succus entericus.

71

How much intestinal juice is secreted per day roughly?

2 litres.

72

What 5 things increase secretion of intestinal juice?

Distension/irritation.
Gastric.
CCK.
Secretin.
Parasympathetic nerve activity.

73

What decreases secretion of intestinal juice?

Sympathetic nerve activity.

74

What do intestinal secretions contain, what do they do and where do they come from?

Mucus - protection/lubrication - goblet cells.
Aqueous salt - enzymatic digestion - mostly from the crypts.
No digestive enzymes.

75

How is chyme chopped up in the small intestine?

Segmentation. Chops and moves the chyme back and forth. Caused by contraction and relaxation of segments of circular muscle.

76

When is segmentation most vigorous?

After a meal, very little or none in between.

77

What primarily activates segmentation in the duodenum?

Distension by entering chyme.

78

What triggers segmentation in the empty ileum?

Gastric from the stomach (gastoileal reflex).

79

How many segmentation contractions does the duodenum have?

12 per min.

80

How many segmentation contractions does the ileum have?

9 per min.

81

What does the differing number is segmentation contractions in the duodenum and ileum result in?

Aboral movement of contents.

82

How long does movement take through the small intestine and what does this allow?

3-5 hours, allows for absorption.

83

What two types of peristalsis occur in the inter digestive or fasting state?

A few localised contractions and the migrating motor complex (MMC).

84

What is the migrating motor complex and what does it do?

Strong peristaltic contraction of entire length of intestine. Clears digested debris, epithelial cells etc. has a housekeeper function.

85

How often does MMC occur?

90-120 mins.

86

What inhibits MMC?

Feeding and vagal activity.

87

What triggers MMC?

Motilin.

88

What suppresses MMC?

Gastric and CCK.

89

What can macrolide antibiotics mimic and what does this cause?

Mimic the action of motilin and causes unpleasant GI disturbances.

90

What are the endocrine secretions of the pancreas and where do they go?

Insulin and glucagon, go into the bloodstream.

91

What are the exocrine secretions of the pancreas, what cells make them and where do they go?

Digestive enzymes form acinar cells.
Aqueous NaHCO3 solution from duct cells.
Both are secreted to the duodenum as pancreatic juice.

92

What kind of cells do pancreatic ducts and acini contain?

Duct cells.
Alpha, beta and delta cells.
Islets of langerhans.
Acinar cells.
PP cells.

93

What pancreatic enzymes are there?

Proteases - trypsinogen, chymotrypsinogen and procarboxypeptidase.
Pancreatic amylase.
Pancreatic lipase.

94

Where are enzymes stored in pancreatic acinar cells?

Zymogen granules.

95

What happens to the pancreatic proteases once they arrive in the duodenum?

Trypsinogen is turned into trypsin by enterokinase from mucosal cells.
Then chymotrypsinogen is turned into chymotrypsin by trypsin.
Procarboxypeptidase is also turned into carboxypeptidase by trypsin.
Trypsin can also autocatalyse trypsinogen to trypsin.

96

What are the three inactive pancreatic enzymes?

Trypsinogen, chymotrypsinogen and procarboxypeptidase.

97

What are the three active versions of the pancreatic proteases?

Trypsin, chymotrypsin and carboxypeptidase..

98

What do pancreatic duct cells secrete?

1-2 litres of Alkaline HCO3 rich fluid per day. Into the duodenum.

99

What is the function of the alkaline fluid secreted by pancreatic duct cells?

Neutralises chyme.
Provides optimum pH for pancreatic enzymes.
Protects the mucosa from erosion by the acid.

100

What are the three phases of the control of pancreatic secretion?

Cephalic, gastric and intestinal.

101

What is the cephalic phase of the control of pancreatic secretion?

Mediated by the vagal stimulation of mainly acinar cells. Makes up about 20% total secretion.

102

What is the gastric phase of the control of pancreatic secretion?

Gastric distension evokes a vasovagal reflex resulting in parasympathetic stimulation of acinar and duct cells. Makes up a total of 5-10% of the secretion.

103

What is the intestinal phase of the control of pancreatic secretion?

Makes up 70-80% of total secretion.
1. Acid in the duodenal lumen causes increased release from S cells of secretin. The secretin is then carried in the blood to pancreatic duct cells. This causes increased secretion of aqueous NaHCO3 solution into the duodenal lumen which neutralises the acid.
2. Fat and protein in the duodenal lumen causes increased CCK release from I cells. CCK is then carried in the blood towards pancreatic acinar cells which causes increased secretion of digestive enzymes into duodenal lumen, which digests the fat and protein.

104

How much bile is produced per day?

0.6-1.2 litres per day.

105

What sphincter prevents bile form entering the duodenum?

Oddi.

106

What stimulates the gall bladder to release bile and what happens?

Chyme in the duodenum stimulates release, the smooth muscle in the wall of the gallbladder contracts and the sphincter of Oddi opens.

107

What cells add secretions to bile?

Hepatocytes and bile duct cells.

108

Where is secretin carried to by the blood and what does this result in?

To the pancreatic duct cells - causes increased secretion of NaHCO3.
To the hepatocytes - causes increased secretion of NaHCO3 rich bile.
Also causes d creased gastric secretion and decreased gastric emptying.

109

Where all is CCK in the blood carried to and what are the results?

Pancreatic acinar cells - increased secretion of digestive enzymes.
Gall bladder and sphincter of Oddi - causes contraction of the gall bladder and relaxation of the sphincter of Oddi.
Also causes decreased gastric emptying and secretion.

110

What endogenous sources do we get proteins from?

Digestive enzymes and dead cells from the GI tract.

111

What different kinds of carbs do we get from our diet?

Starch, cellulose, glycogen and disaccharides.

112

What two types of digestion occur in the small intestine?

Luminal and membrane digestion.

113

What mediates digestion at the membrane?

Enzymes situated at the brush border of epithelial cells.

114

What two membranes do enterocytes have?

The apical membrane (brush border) and the basolateral membrane (facing the interstitium).

115

What is the name given to the overall process of digestion and absorption?

Assimilation.

116

How is glucose digested and absorbed in the small intestine?

Is doesn't have to be digested, it is just absorbed.

117

How is protein digested and absorbed in the small intestine?

Protein undergoes luminal hydrolysis from the polymer to the monomer e.g. Proteins to amino acids which are then absorbed.

118

How is sucrose digested and absorbed in the small intestine?

Broken down to fructose and glucose by hydrolysis at the brush border and then absorbed.

119

How is peptides digested and absorbed in the small intestine?

They undergo intracellular hydrolysis in the enterocytes, so are absorbed as peptides and cross to the interstitium as amino acids.

120

How is triacylglycerols digested and absorbed in the small intestine?

Broken down to fatty acids and glycerol by luminal hydrolysis. Absorbed into enterocytes and then re synthesised inside the enterocytes to pass into the interstitium as triacylglycerol.

121

What three areas are carbs digested?

Mouth, stomach and the duodenum.

122

What breaks down carbs in the mouth?

Salivary alpha amylase.

123

What breaks down carbs in the stomach?

Salivary alpha amylase within the bolus.

124

What breaks down carbs in the duodenum?

Pancreatic alpha amylase that are free in the lumen.
Oligosaccharidases on the brush border membrane.

125

What are some Oligosaccharidases?

Isomaltase, sucrase, lactase and maltase.

126

What causes lactose intolerance?

Deficiency in lactase.

127

What is amylose?

Straight chain starch with alpha 1,4 linkages.

128

What is amylopectin?

Branched chain starch with alpha 1,4 linkages and alpha 1,6 linkages.

129

What is glycogen?

A branched chain polysaccharide with alpha 1,4 and alpha 1,6 linkages.

130

What is sucrose?

Table sugar made of glucose plus fructose. Contains alpha 1,2 linkages.

131

What is lactose?

Milk sugar comprising of glucose and galactose. Contains beta 1,4 linkages.

132

What are two monosaccharides?

Glucose and fructose.

133

What must carbohydrates by converted to in order to be absorbed?

Monosaccharides.

134

What are the final products of carb digestion?

Glucose, galactose and fructose.

135

Where does absorption of the final products of carb digestion occur?

Duodenum and jejunum.

136

How are the final products of carb digestion absorbed?

Two step process involving exit from the enterocytes via the apical and basolateral membranes.
Glucose and galactose are absorbed by secondary active transport mediated by SGLT1.
Fructose by facilitated diffusion by GLUT5.
Exit for all monos is facilitated diffusion by GLUT2.

137

What is the sequence of carbohydrate digestion?

Starch is broken down to Oligosaccharides by alpha amylase (salivary and pancreatic).
Oligosaccharides are not absorbed but are joined by lactose and sucrose from the diet.
These are then broken down by Oligosaccharides to monosaccharides. And joined by glucose and fructose from the diet and then absorbed.

138

What are some Oligosaccharides?

Lactase, maltase and sucrase-isomaltase.

139

What is alpha amylase and what does it do?

It is an endoenzyme.
It breaks down linear internal alpha1,4 linkages but not terminal alpha 1,4 linkages. Hence no production of glucose.

140

What can alpha amylase not cleave?

Alpha-1,6 linkages at branch points or alpha-1,4 linkages adjacent to branch points.

141

What are the products of alpha-amylase breakdowns?

Linear glucose Oligocene e.g. Maltotriose, maltose.
And also alpha limit dextrins.

142

What are the 6 steps in the mode of operation of SGLT1?

1. 2 na+ binds.
2. Affinity for glucose increases and it binds.
3. Na+ and glucose translocation from extracellular to intracellular.
4. 2 Na+ dissociate and affinity for glucose fails.
5. Glucose dissociates.
6. Cycle is repeated.
This means that sodium is also transported into the cytosol.

143

What is an oligosaccharidease?

An integral membrane protein with a catalytic domain facing the GI lumen.

144

What does lactase do?

Breaks down lactose to glucose and galactose.

145

How are maltose, maltotriose and alpha limit dextrins changed into glucose?

All Oligosaccharidases cleave the terminal alpha-1,4 linkages off.

146

What does maltase do in addition to normal breakdown of substances to glucose?

Can degrade alpha-1,4 linkages in straight chain Oligomers up to one monomers in length.

147

What does sucrase do in addition to normal breakdown of substances to glucose?

Specifically responsible for hydrolysing sucrose to glucose and fructose.

148

Why is isomaltase unique?

Only enzyme that can split branching alpha-1,6 linkages of alpha limit dextrins.

149

What speeds are the hydrolysis reactions of Maltese, sucrose, isomaltase and lactase?

Maltese, sucrose and isomaltase occur at a faster rate than the transport of the released monomers. Lactase the rate of hydrolysis is rate limiting in assimilation.

150

What normally happens to lactase activity post weaning and why?

It is usually lost. But humans have a variable degree of lactase persistence. Partially due to polymorphisms in the MCM6 gene that regulates expression of the lactase gene.

151

What three types of lactase deficiency are there?

Primary, secondary and congenital.

152

What causes primary lactase deficiency? (Hypolactasia)

Due to lack of lactase persistence allele and is the most common form worldwide.

153

What causes secondary lactase deficiency? (Hypolactasia)

Damage to/ infection of the proximal small intestine.

154

What causes congenital lactase deficiency? (Hypolactasia)

Rare autosomal recessive disease. Have no ability to digest lactose from birth.

155

When does hypolactasia cause problems.

If lactose containing food overwhelms the remaining lactase enzyme. This causes lactose to be delivered to the colon.

156

What do colonic microflora produce if exposed to lactose?

SCFA which can be absorbed.
H2 - which can be detected in the breath of lactase deficient individuals following a lactose challenge.
CO2
Methane

157

What do the products formed by the colonic flora of lactose intolerant individuals cause?

Bloating, abdominal pain and flatulence.

158

What does undigested lactose cause?

Acidification of the colon. Increased osmotic load and loose stools and diarrhoea.

159

How many major pathways of protein digestion absorption are there?

4.

160

What are the four pathways of protein breakdown/assimilation?

All have protein to peptides to amino acids to amino acid on enterocytes to amino acid in the blood.
1. Uses luminal enzymes then apical membrane transformers then basolateral membrane transporters.
2. The same except brush border enzymes in between the first two.
3. The same as number 1 but intracellular hydrolysis occurs in between the last two.
4. The peptide is transported out of the enterocyte without intervening intracellular hydrolysis by proteases.

161

What happens to proteins in the stomach?

Hcl begins to denature them. Pepsin cleaves proteins into peptides.

162

What is pepsin and what pH does it like?

Cleaves proteins. Is an endopeptidase with preference for bonds between aromatic and larger neutral amino acids. It's not essential for protein digestion. Likes pH 1.8 to 3.5.

163

What are the two function categories of pancreatic proteases in the duodenum?

Endopeptidase sand exopeptidases.

164

What are the three endopeptidases and what do they do?

Trypsin, chymotrypsin and elastase.
They phreak down peptides into oligopeptides (2-6) amino acids long.

165

What are the two exopeptidases? And what do they do?

Procarboxypeptidase A and B. Break down proteins into single amino acids.

166

What are the final products of protein breakdown?

Amino acids, dipeptides, tripeptides, oligopeptides and some intact proteins.

167

What completes protein digestion?

Additional proteases present at the brush border.

168

What two types of brush border exopeptidases are there?

Aminopeptidases and carboxypeptidases.

169

Why are their numerous brush border peptidases?

Because each attacks a limited number of peptide bonds and the oligopeptides to be digested are very varied in structure.

170

What do brush border peptidases have an affinity for?

Larger oligopeptides. 3-8 amino acids.

171

What are the numbers of cytoplasmic peptidases and what do they do?

Less numerous than those at the brush border. Primarily hydrolyse dipeptides or tripeptides.

172

How many mechanisms of amino acid absorption are present at the brush border and what categories do they fall into?

7.
5 na dependent cotransporters mediating uphill movement.
2 na independent.

173

How many mechanisms of amino acid absorption are present at the basolateral membrane and what categories do they fall into?
What do these categories say about the movement of amino acids?

5.
3 mediate effluent and are na independent.
2 mediate influx and are na dependent.
Net movement is therefore bidirectional.

174

How are di tri and tetra peptides absorbed?

h+ dependent mechanisms at the brush border (co-transport).
Further hydrolysed to amino acids within the enterocyte.
Na + independent systems at the basolateral membrane (facilitated transport).

175

What kinds of lipid do we get from our diets?

Fats/oils (triacylglycerols), phospholipids, cholesterol and cholesterol esters. Fatty acids.

176

What is the solubility of ingested lipids?

Insoluble e.g. Cholesterol esters or poorly soluble.

177

What are the three phases in lipid digestion, how important are they and what do they do?

Mouth (lingual phase) unimportant.
Stomach (gastric phase)- modestly important.
Small intestine. Most important. Fats emulsified by bile and pancreatic lipase which hydrolyse TAGs to mono glycerine and free fatty acids.

178

How are TAGS digested by lipase in the stomach?

Heat and stomach movement mixes fats with gastric lipase forming an emulsion.
Hydrolysis initially slow due to largely separate aqueous/lipid interface.
As hydrolysis proceeds rate increases as produced fatty acids act as surfactants breaking down lipid globules aiding emulsification.
Emulsified fats are ejected from the stomach to the duodenum.

179

What juices assist in TAG breakdown in the duodenum and what do they do?

Pancreatic lipase aided by bile salts. HCO3 in pancreatic juice neutralises stomach acid and provides a suitable pH for optimal enzyme action.

180

Describe breakdown of triglycerides?

Triglyceride to diglyceride and free fatty acids by gastric lipase and water.
Free fatty acids stimulate CCK release from duodenum and secretion of pancreatic lipase.

181

What do bile salts do?

Act as detergents to emulsify large lipid droplets to small ones. They are ampiphatic. They increase the surface area for attack by pancreatic lipase.

182

What two things can failure to secrete bile salts result in?

Lipid malabsorption - streatorrhoea (fat in faeces).
Secondary vitamin deficiency due to failure to absorb lipid vitamins.

183

What is a problem created by bile salts and how is this solved?

Block access of pancreatic lipase to hydrophobic core of small lipid droplets.
Problem solved by colipase which binds to the bile salts and lipase and allows them access to the do and triglycerides.

184

What is colipase?

An amphiphatic polypeptide secreted with lipase by the pancreas.

185

What is the product of pancreatic lipase digestion?

2 mono glycerine sand free fatty acids.

186

What are the final products of lipid digestion stored in and released from?

Mixed micelles.

187

What do mixed micelles contain?

Cholesterol, monoglycerides, fatty acids, phospholipids and bile salts surrounding a hydrophobic core.

188

How are fatty acids and monoglycerides transferred from micelles to enterocyte membranes?

Passive diffusion.

189

How do short chain fatty acids exit enterocytes?

They diffuse through and exit the basolateral membrane to enter villus capillaries.

190

How do long chain fatty acids exit enterocytes?

They are re synthesised to triglycerides in the ER and are then incorporated into chylomicrons.

191

How are chylomicrons formed?

Mono and free fatty acids resynthesised to triglycerides in the enterocyte ER.
Cholesterol esters are added to make phospholipids.
This then makes a nascent cholymicron.
Apolipoprotein are added to make a cholymicron.
They then leave by executors is and are absorbed by the central lacteals.

192

How do cholymicrons enter the systemic circulation?

Into the subclavian vein via the thoracic duct.

193

Where are chylomicrons triglycerides metabolised? And by what?

In the capillaries, particularly muscle and adipose tissue.
By lipoprotein lipase on the surface of endothelial cells.

194

What happens to the free fatty acids and glycerol released initially after chylomicrons triglyceride metabolism?

They are bound to albumen and taken up by the tissues.

195

After metabolism of chylomicron triglycerides and binding to albumen, what is left over?

Chylomicron remnant. Containing phospholipids and cholesterol.

196

What happens to chylomicron remnants?

Undergo endocytosis by hepatocytes. The released cholesterol is either: stored, secreted unaltered in bile or oxidised to bile salts.

197

How is cholesterol absorbed?

Mainly due to transport by endocytosis in Clatherin coated pits by Niemann-Pick like 1 protein. (NPC1L1).

198

How does Ezetimibe work?

Binds to NPC1L1 and prevents internalisation and cholesterol absorption.

199

What are the two types of calcium absorption and where do they occur?

Passive- paracellular - whole length of small intestine.
Active - transcellular - mainly duodenum and upper jejunum.

200

What is active calcium absorption regulated by?

Calcitriol and parathyroid hormones.

201

What is the storage form of iron?

Ferratin.

202

What transforms iron into ferratin?

Apoferratin.

203

What transfers iron into the enterocytes and what inhibits it?

Ferroportin and hormone hepcidin, which is released from the liver when body iron levels are high stops it.

204

What transfers iron out of enterocytes?

Divalent metal transporter. It is coupled to H+ transport.

205

What is another name for vitamin B12?

Cobalamin.

206

Why is efficient vitamin B12 required?

It is only present in tiny amounts in the diet.

207

What are the steps in vitamin B12 absorption?

Vitamin B12 in food.
Salivary glands secrete haptocorin.
Stomach acid releases B12 from food.
Haptocorin binds to it in stomach.
Stomach parietal cells release intrinsic factor.
Haptocorin digested by pancreatic proteases in the SI releasing B12.
Binds to intrinsic factor in SI.
Complex of two absorbed in terminal ileum by endocytosis.

208

What are the fat soluble vitamins and how are they absorbed?

ADEK. Incorporated into micelles.
Passively transported into enterocytes. Incorporated into chylomicrons or VLDL's, then distributed by intestinal lymphatics.

209

How are water soluble vitamins absorbed?

Transport proteins in apical membrane similar to monosaccharides etc.

210

Name some water soluble vitamins?

B9, C and H.

211

What is another name for vitamin B9?

Folic acid.

212

What is another name for vitamin C?

Ascorbate.

213

What is another name for vitamin H?

Biotin.

214

What causes obesity?

We consume more calories than we expend. But it's not a single disorder it has multiple causes.

215

What are the three major components in development of obesity?

Genetics, environment and energy intake/expenditure imbalance.

216

How does the CNS influence energy balance and body weight?

Behaviour - feeding and physical activity.
ANS activity - regulates energy expenditure.
Neurone doctrine system - secretes hormones

217

What centre in the brain integrates feeding behaviour?

The hypothalamus.

218

What do lesions in different areas of the hypothalamus cause in relation to weight?

Ventromedial hypothalamus lesions cause obesity.
Lateral lesions cause leanness.

219

What three basic concepts underlie the weight control system?

Satiety signalling, adiposity negative feedback signalling and food reward.

220

What is satiation?

Sensation of fullness generated after a meal.

221

What is satiety?

Period of time between the termination of one meal and the initiation of the next.

222

What is adiposity?

The state of being obese.

223

What are 5 satiation signals?

Cholecystokinin.
Peptide YY.
Glucagon like peptide 1 GLP-1
Oxyntomodulin OXM
Obestatin.

224

What is CCK in relation to satiation signalling?

Secreted by enteroendocrine cells in the duodenum and jejunum.
It is released in proportion to the lipids and proteins in a meal.it sends signals to the hindbrain and stimulates it directly.

225

What is peptide YY?
.

Secreted by endocrine mucosal L cells of GI tract. Levels increase rapidly after eating. It slows emptying and reduces food intake

226

What is GLP1 and what does it do?

It is product of the proglucagon gene. From GI L cells in response to eating. Also inhibits gastric emptying and reduces food intake.

227

What is oxytomodulin and what does it do?

From proglucagon gene and released from oxyntic cells of SI after a meal. It suppresses appetite.

228

What is obestatin and what does it do?

Peptide produced from a gene that encodes gherlin. Released from cells lining the stomach/small intestine. Reduces food intake by possibly antagonising the actions of gherlin.

229

What is gherlin?

A octanolyated peptide hunger signal.

230

What secretes gherlin?

Oxyntic cells in the stomach.

231

What increase or decreases gherlin levels?

Increases - before meals, fasting and hypoglycaemia.
Decreased after meals.

232

What does gherlin do?

Peripheral gherlin stimulates food intake and decreases fat utilisation.

233

What substances increase food intake when injected into hypothalamic centres?
How long do they last?

Glutamate, gaba and opioids. Effects are modest and shortlasting.

234

What substances decrease food intake when injected into hypothalamic centres?

Monoamines.

235

What two adiposity signal hormones act on the hypothalamus?

Leptin which is made by and released from fat cells.
Insulin.

236

How do the adiposity signal hormones work?

Levels in blood increase as fat is stored. They inform the brain to alter the energy balance. Eat less and increase energy burn. This malfunctions in the obese state?

237

What does reduced leptin mimic?

Starvation causing unrestrained appetite.

238

What is leptin and what seven biological roles does it have?

It is a pleiotropic hormones.
Influences food intake and energy burn.
Influence peripheral glucose homeostasis and insulin sensitivity.
Helps maintain the immune system.
Maintains the reproductive system.
Angiogenesis.
Tumourigenesis.
Bone formation.

239

What is the role of insulin in relation to adiposity?

Circulates in proportion to body adiposity. There is a transport system for insulin to enter the brain and lots of receptors in the hypothalamus. Intercerebroventricular insulin inhibits food intake and decreases body weight in rodents. There are neurone specific deflections of insulin receptors in obesity.

240

What pathway plays an important role in food reward?

Dopamine pathways.

241

What areas of the brain are implicated in substance abuse and drug addiction?

The ventral tegmental area. Composed of : nucleus accumbens, striatum and the substantia nigra.

242

What are the functions of dopamine?

Reward, pleasure and euphoria, motor function, compulsion and preservation.

243

What are the functions of serotonin?

Mood, memory processing, sleep and cognition.

244

What limits the use of therapeutical leptin?

Severe leptin resistance, especially in diet induced obesity.

245

What are the two main theories for leptin resistance?

Defective leptin transport in brain.
Altered signal transduction following leptin binding to its receptor.

246

What are other names for orlistat? What does it do?

Xenical or Alli.
Inhibits pancreatic lipase and so inhibits triglyceride absorption.
Reduces efficacy of fat absorption in the small intestine.
Side effects include cramping and severe diarrhoea
Need vitamin supplements.
Not long term efficient
Rebound weight.

247

What are three new anti obesity drugs coming on the market?

Lorcaserin, qysmia and contrave.

248

What does bariatric surgery result in?

Frequently Complete resolution of type 2 diabetes.
May affect secretion of GLP1, PYY and Gherlin.

249

Where is brown adipose tissue in adults? (BAT)

Neck, clavicle and spinal cord.

250

What is adaptive thermogenesis?

Inducible browning of white adipose tissue (WAT).

251

What is another name for Liraglutide? What does it do?

Saxenda.
Type 2 DM treatment also causes weight loss.
GLP-1 receptor agonist, therefore a satiety peptide.
Higher doses for weight loss than for DM.
Has to be injected, mechanism for weight loss unclear.
Some concerns over thyroid and pancreatic cancer.

252

What is a tissue?

Group of cells with similar structure and a specialised function.

253

What is an organ?

Two or more tissues working together to carry out a specialised function.

254

What is a body system?

Group of organs that perform related functions and work together to achieve a common goal.

255

Where do many pharmacological agents act?

At the level of the cell membrane.

256

What are the two categories of homeostatic control systems?

Intrinsic - local controls inherent to an organ.
Extrinsic - regulatory mechanisms initiated outside an organ, accompanied by nervous and endocrine systems.

257

What is a feedforward system?

Term used for responses made in anticipation of a change.

258

What is feedback?

Response made after change is detected.

259

What are the two types of feedback systems?

Negative and positive.

260

What is negative feedback?

Primary system. Opposes initial change.
Promotes stability by regulation of a controlled variable through flow of information along a closed loop.

261

What is the plasmalemma?

Fluid lipid bilayer embedded with proteins - cell membrane.
It has a tri laminar appearance under the microscope.

262

What are the different parts of a phospholipid?

Negatively charged phosphate head and uncharged charged lipid tails. One is bent.
Head is polar and hydrophilic.
Tail is non polar and hydrophobic.

263

What are carrier or transport proteins?

Span the membrane.
Exhibit substrate specificity - accept only a particular ion or closely associated group.

264

What are docking marker acceptors?

Located on the inner membrane surface. Interact with secretory vehicle to allow exocytosis.

265

How does a vehicle from the Golgi apparatus leave the cell?

Secretory vesicle is formed from membrane of outer most Golgi sack.
Budding breaks the vesicle off.
It is then up coated in the cytosol.
It then docks at a docking marker acceptor and is discharged.

266

Where are receptors most commonly found and what do they do?

Commonly on outer surface. Bind to molecules in a specific manner.

267

What are CAMS?

Cell adhesion molecules.
Proteins like Cadherin and integrity hold cells together.
Also act as a link between internal and external environment.

268

What are self identity markers made out of?

Short carbohydrate chains.

269

What are the three types of specialised cell junctions?

Desmosomes, tight junctions and gap junctions.

270

What are desmosomes?

Adhering junctions that anchor cells together especially in tissues subject to stretching e.g. Skin, heart etc.

271

What is a tight junction?

Join the lateral edges of epithelial cells near their luminal (apical), Membranes.
Can be wither tight or leaky.

272

What is a gap junction?

Communicating junctions that allows the movement of charge carrying ions and small molecules between two adjacent cells.

273

What is an electrochemical gradient?

Both electrical and chemical acting on a molecule at the same time.

274

What two types of driving forces do we have?

Passive or active.

275

What are two forms of passive movement?

Diffusion down either a concentration or an electrical gradient.

276

What are the five factors of Ficks law of diffusion?

Magnitude of the concentration gradient.
Surface area of the membrane that diffusion is occurring across.
Lipid solubility of the substance.
Molecular weight of the substance.
Distance through which diffusion can take place.

277

What is a name for a membrane water channel?

Aquaporin.

278

What is osmolarity?

The concentration of osmotically active particles in a substance.

279

What is tonicity?

The effect a solution has on a cell e.g. Hypo ISO or hyper.

280

What is carrier mediated transport?

Substance binds to a carrier which undergoes a conformational shape to transport the substance.

281

What three characteristics determine the kind and amount of material that can be transported across the membrane by carrier mediated transport?

Specificity.
Saturation - the transport maximum.
Competitions - e.g. Amino acids.

282

What are the two forms of carrier mediated transport?

Facilitated diffusion and active transport.

283

What is facilitated diffusion?

Uses a carrier to transport the substance across the membrane downhill. E.g. With is concentration gradient.
Does not require energy.

284

What is active transport?

Carrier expends energy to move the substance uphill against its concentration gradient.

285

What two types of active transport are there?

Primary and secondary.

286

What is primary active transport?

Energy is directly required to move a substance against its concentration gradient.

287

What is secondary active transport?

Energy is required but not used directly to produce uphill movement. Carrier doesn't use ATP it moves a molecule uphill by using secondhand energy stored in the form of an ion concentration gradient.
The transfer of the solute is always coupled with the transfer of an ion.

288

What is the sodium potassium pump and what numbers do they move?

Primary active transporter in all plasma membranes. 3 Na out for every 2 K in.

289

What are three important roles for the sodium potassium pump?

Helps establish sodium potassium gradient.
Helps regulate cell volume by controlling salutes inside and outside the cell.
Energy used to drive the pump is indirectly used for secondary transport.

290

What are the two mechanisms of secondary transport?

Symport - co-transport.
Antiport - exchange or counter transport.

291

What is symport?

Solute and ion move in the same direction.

292

What is antiport?

Solute and ion move in opposite direction.

293

What is the ion officially called in active transport?

The driving ion.

294

Is vesicular transport active or passive?

Active.

295

What is endocytosis?

Pinching off of membrane to engulf substances.

296

What is exocytosis?

Vesicle fuses with membrane and discharges its contents to the ECF.

297

What is membrane potential?

The difference between the opposite charges at either side of the membrane. It is the charge of the thin layers of fluid on either side of the membrane.

298

What particles cause the membrane potential and why?

The differences in concentration and permeability of key ions. The unequal distribution and permeability on either side make the potential.

299

How is membrane potential written?

Em.

300

When is resting membrane potential constant?

In non-excitable cells and in resting excitable cells.

301

What direction is the concentration gradient for sodium?
What is its relative permeability?

Inward.
1.

302

What direction is the concentration gradient for potassium?
What is its relative permeability?

Outward.
100.

303

What ions is the plasma membrane impermeable to?

Large negatively charged intracellular proteins.

304

Describe the equilibrium potential for potassium.

Concentration gradient is outwards.
The electrical gradient is inwards.
The membrane potential at Ek is -90mv.

305

What is equilibrium potential and how is it written?

When both the electrical and concentration gradients are at equilibrium.
Ek.

306

What does the +/- sign mean in Ek?

Is the polarity of the excess charge on the inside of the membrane.

307

What equation do we use to calculate the equilibrium potential?

The Nernst equation.

Eion = 61log10 times (the concentration of the ion on the outside of the cell divided by the concentration of the ion on the inside).

308

What is the charge inside all cells at rest?

Negative.

309

What is the resting membrane potential for sodium and potassium combined?

-83mv.

310

What equation can be used to calculate the Em for more than one ion?

Goldman Hodgkin Katz.

311

Why is the combined membrane potential of sodium and potassium closer to the Ek of potassium than sodium?

Because potassium is a lot more permeable. As the greater the permeability of an ion the greater the tendency it has to drive the Em towards the ions on equilibrium potential.

312

Describe the equilibrium potential for sodium?

The electrical gradient is inwards.
The concentration gradient is inwards.
The Ek is +61.

313

What is the importance of Em?

Nerve and muscle cells can rapidly change it in response to stimulation allowing action potentials.

314

What is the optimal core body temperature?

37.8 deg.

315

What is the normal range of tympanic temperature?

35.5-37.8 degrees.

316

When can normal body temperature vary?

Different in different people.
Varies during the day - lowest in the morning.
Exercise emotions stress etc.
Highest after ovulation in women

317

How do we gain heat from the internal environment?

Metabolic heat.

318

How categories of heat gain do we have from the external environment?

Radiation, convection and conduction.

319

What categories of heat loss can we have?

Convection, conduction, radiation and evaporation.

320

What is metabolic heat?

Duration of metabolic fuel derived from food in the body.

321

What is the basal metabolic rate?

Minimum amount of energy required to maintain bodily functions. It leads to a basic level of heat production.

322

What hormones can increase the basal metabolic rate?

Adrenaline, NORAD and thyroxine.

323

What is non shivering thermogenesis?

Metabolism of brown fat giving heat.

324

What is radiation?

Emission of heat by electromagnetic waves. They are transformed into heat upon striking another surface.

325

Does the human body emit or absorb radiant heat? What affects its net transfer?

Both. Transfer dependent on relative temperature of body and surroundings including the sun.

326

What is the human body's greatest category of heat loss?

Radiation, about 50%.

327

What is conduction?

Transfer of heat between objects in contact?

328

What does heat conduction depend on?

Temperature gradient and thermal conductivity.

329

What is convection?

Transfer of heat by currents e.g. Air or water.

330

How does convection carry heat away from the body?

Combines with conduction.
Air next to body warmed by conduction.
Warmed air becomes less dense and rises.
Cooler air moves in and the same happens.

331

What is the wind chill factor?

Forced air movement increasing heat loss by convection conduction method. Air trapping clothing lowers convection loss.

332

What is evaporation in humans?

Energy is required to change water on surfaces into vapour e.g. In airways. This energy comes from the body and so results in evaporative heat loss.
It is continuous and passive.
We can have active evaporative heat loss e.g. Sweating.

333

What affects the amount of heat loss through evaporation?

Relative humidity of the atmosphere.

334

Where are our central thermoreceptors?

Hypothalamus and abdominal organs etc.

335

Where is the control centre?

Hypothalamus.

336

Where are peripheral thermoreceptors?

In the skin.

337

Where are our thermal effectors?

Skeletal muscle, skin arterioles and sweat glands.

338

What kind of inputs and outputs does the hypothalamus have?

Neural and hormonal.

339

What kind of neural inputs does the hypothalamus receive?

Ones from negative feedback receptors for temperature regulation.

340

What does the hypothalamus do?

Acts as the body's thermostat maintaining the body at a temperature set point.

341

What parts of the hypothalamus are stimulated by heat and cold?

Heat = anterior hypothalmic centre.
Cold = posterior.

342

What does the hypothalamus have neural connections with?

Lambic system, cerebral cortex, motor neurone and the sympathetic nervous system.

343

What does the posterior hypothalamus cause?

Shivering, vasoconstriction, postural changes etc.

344

What does the anterior hypothalamus cause?

Sweating, vasodilation etc.

345

What temperatures are described as fever?

38-40 degrees.

346

What temperature is thought of as hyperthermia?

More than 40 deg.

347

What temperature is thought of a hypothermia?

Under 35deg.

348

How does the hypothalamus react to infection?
What are the different steps?

Macrophages release chemicals in response to infection/inflammation that act as endogenous pyrogens.
Endogenous pyrogen stimulate prostaglandin release in hypothalamus.
Prostaglandins cause thermoregulatory centre to reset at a higher temperature.
The hypothalamus initiates a cold response to heat the body.
Body temp increases to new set point resulting in fever.
Pyrogen release or cessation lowers the set point again.
Hypothalamus initiates hot response to cool body again.

349

What is blood pressure?

The outward hydrostatic pressure exerted by the blood on the vessel walls.

350

What is MAP and how do we calculate it?

Mean arterial blood pressure.
The average arterial blood pressure during one cardiac cycle.
MAP = ((2x diastolic) + systolic) divided by 3.
MAP = diastolic + 1/3 of pulse pressure.

351

What is pulse pressure?

SBP - DBP.

352

What is the normal range of MAP?

70-105.

353

What is the minimum MAP we need to perfume the coronary arteries, brain and kidneys.

60 mmHg.

354

Why is MAP not just an average of SBP and DBP?

Because diastole is twice as long as systole.

355

Why do we hear korotkoff sounds?

Can't hear normal laminar flow.
When cuff pressure exceeds blood pressure, no sound is heard as there is no blood flow.
When we decrease the cuff pressure, blood flow is turbulent and can be heard.
When I'd falls below diastole we can't hear anything again.

356

What is the minimum systolic needed to feel a radial pulse?

Over 80 mmHg.

357

What sound do we record diastolic blood pressure at when taking bp?

The 5th korotkoff sound.
When sound disappears.

358

Where are baroreceptors situated?

In the arch of the aorta and the carotid sinus.

359

What are baroreceptors?

Mechanoreceptors that are sensitive to stress.

360

How do baroreceptors communicate a change in blood pressure?

Firing rate in the baroreceptors affront neurones increases with increased blood pressure (MAP) and vice versa.

361

Where are baroreceptor signals received?

The cardiovascular control centre in the medulla of the brainstem.

362

What is the 1st synapse for all CVS afferents in the medulla?

The nucleus tractus solitarus. NTS.

363

What does the NTS do?

Relays info to other regions of the brain e.g. Medulla, hypothalamus etc. it generates a vagal outflow to the heart and regulates spinal sympathetic neurones.

364

What is MAP in relation to TPR etc.

MAP = cardiac output x total peripheral resistance.

365

What is cardiac output and how do we calculate it?

The volume of blood pumped by each ventricle of the heart per minute.
CO = stroke volume x heart rate.

366

What is the stroke volume?

Volume of blood pumped by each ventricle per minute.

367

What is total peripheral resistance?

Sum resistance of all peripheral vasculature in the systemic circulation.

368

What can the body change to alter MAP?

Heart rate, stroke volume or TPR.

369

What are the major resistance vessels?

The arterioles.

370

What is MAP like in the small blood vessels?

Very low in capillaries and practically 0 in venules and veins.

371

What is the ability of the heart to control its own rate called?

Autorhythmicity.

372

What is the nervous supply of the heart? What transmitters does it use? What receptors are activated?

Sympathetic - increases HR - noradrenaline acts on beta 1 receptors.
Parasympathetic - vagus nerve slows HR. Acetylcholine on muscarininc receptors.

373

What anatomical parts of the heart does sympathetic nerves innervate and what is the result of stimulation on stroke volume?

Ventricular myocardium. Stimulation increases the force of contraction and increases stroke volume. Also supplies the SA and AV nodes.

374

How does the parasympathetic nervous system decrease MAP through the heart?

Decreases HR which decreases CO which decreases MAP.

375

How does the sympathetic nervous system decrease MAP through the heart?

Increases HR which increases CO and therefore MAP.
plus it increases ventricular myocardium contractile strength which increases stroke volume, which increases CO and therefore MAP.

376

What does the sympathetic nervous system do to the arterioles to increase MAP?

Causes vasoconstriction in the arterioles, which increases TPR and therefore MAP.

377

How does sympathetic stimulation of the veins alter MAP?

Causes vasoconstriction, which increases venous return, which increases stroke volume, which increases CO and therefore MAP.

378

What nerves supplies vascular smooth muscle, what is the neurotransmitter and what is the receptor?

Sympathetic nerve fibres. Transmitter is norad. Receptors are alpha receptors.

379

What is vasomotor tone?

Vascular smooth muscle is partially constricted at rest. Caused by tonic discharge of sympathetic nerves resulting in continuous release of norad.

380

What two areas have significant parasympathetic innervation of smooth muscle?

The penis and clitoris.

381

What is the baroreceptor reflex?

Short term control of MAP.

382

What kind of feedback does the baroreceptor reflex use?

Negative feedback.

383

What is the baroreceptor reflex response to a drop in BP?

Decreased baroreceptor discharge is communicated to medulla.
Medulla coordinates decreased vagal activity, increased cardiac sympathetic activity and increased sympathetic vascular constrictor tone.
These all increase TPR and CO and therefore increase ABP.

384

What is the baroreceptor reflex response to an increase in BP?

Increased baroreceptor discharge is communicated to medulla.
Medulla coordinates increased vagal activity, decreased cardiac sympathetic activity and decreased sympathetic vascular constrictor tone.
These all decrease TPR and CO and therefore decrease ABP.

385

What happens to baroreceptor firing with sustained high BP?

It decreases. They are reset and only continue to fire again if it goes above the new set point.

386

How is MAP controlled in the longer term?

Largely by control of blood volume by hormones.

387

What happens to venous return when a person stands up from lying?

It decreases due to gravity.

388

What happens to MAP when a person stands up from lying position?
What mechanisms counteract this?

It transiently decreases.
Causes decreased firing of baroreceptors. Causes vagal tone to the heart to decrease and sympathetic tone to increase. Causes increases TPR and CO and so increases BP.
This causes rapid correction of the transient fall.
Causes a slight increase in DBP when healthy people stand from lying.

389

What causes postural hypotension?

Failure of baroreceptor responses to gravitational shifts in blood pressure.

390

What percentage of body weight is normally made up of water?

60%.

391

What are the different fluid compartments and there ratio of the water?

Intracellular 2/3rds and extracellular 1/3.

392

What volumes comprise the ECF?

Plasma volume and interstitial fluid volume.

393

What happens to the fluid compartments if plasma volumes fall?

Fluid is shifted from the interstitial compartment to the plasma compartment.

394

What two main factors affect extracellular fluid volume?

Water excess or deficit and salt excess or deficit.

395

What three hormones regulate extracellular fluid volume?

Rennin angiotensin aldosterone system RAAS.
Atrial natriuretic peptide ANP.
Antidiuretic hormone ADH.

396

What does RAAS play an important role in?

Regulation of plasma volume and TPR and therefore MAP.

397

What are the steps between rennin release and angiotensin II?

Rennin released from kidneys, stimulates the formation of angiotensin 1 in the blood from angiotensinogen which is produced in the liver.
Then angiotensin converting enzyme (ACE) convert angiotensin 1 to 2.

398

What does angiotensin 2 do?

Stimulates release of aldosterone from the adrenal cortex.
Also causes vasoconstriction (increased TPR),
Stimulates thirst,
Stimulates ADH release.

399

What does aldosterone do?

Increases blood pressure, increases plasma volume and increases sodium and water reabsorption in the kidneys by decreasing sodium and water excretion.

400

What is the rate limiting step for RAAS?

Regulated by mechanisms which stimulates rennin release from the juxtaloglomerular apparatus in the kidney.

401

What three mechanisms stimulate rennin release from the juxtaloglomerular apparatus in the kidney?

Renal artery hypotension caused by systemic hypotension.
Stimulation of renal sympathetic nerves.
Decreased sodium in renal tubular fluid.

402

What senses decreased sodium in the renal tubular fluid?

Macula densa, which are specialised cells of the kidney tubules.

403

What is the juxtaglomerular apparatus?

Region in the kidney comprised of macula densa extraglomerular mesangial cells and granular cells.

404

What cells release rennin?

Granular cells in the kidney.

405

What is ANP, where is it synthesised and stored and what does release cause?

A 28 amino acid peptide, made by atrial myocytes. Released in response to atrial distension (hypervolaemic states). Cause excretion of water and salt from the kidneys. It also acts as a vasodilator decreasing BP and renin release. Therefore is counter regulates the RAAS system.

406

What is another name for ADH?

Vasopressin.

407

What is ADH?

Peptide hormone synthesised by the hypothalamus and stored in the posterior pituitary.

408

What stimulates release of ADH?

Reduced extracellular fluid volume and increased extracellular fluid osmolarity.

409

What monitors plasma osmolarity?

Osmoreceptors, that are mainly located in the brain close to the hypothalamus.

410

What does ADH do?

Acts on the kidney tubules to increase reabsorption of water. This increases extracellular and plasma volume and cardiac output and therefore Bp.
Also causes vasoconstriction increasing TPR and BP.

411

What is a glucose obligate organ and what can it use in times of starvation?

The brain.
Ketone bodies.

412

What is the brain glucose obligate?

It stores little glycogen and the blood brain barrier prevents plasma fatty acids crossing it.

413

What is hypoglycaemia a blood sugar of?

Under 2.5

414

What minimum blood sugar do we want?

4 is the floor.

415

What do the different pancreatic islet of langerhans cells release?

Alpha cells release glucagon.
Beta cells release insulin.
Gamma cells release somatostatin.

416

What happens to glucose and pancreatic hormones in the absorptive (fed) state?

Glucose rises. Insulin rises and glycogen falls.

417

What does insulin do?

Favours anabolism. Stimulates conversion of glucose to glycogen, fatty acids to triglycerides and amino acids to proteins.
Insulin is the hormone of the fed state.

418

What does glucagon do?

Favours catabolism. Stimulates conversion of glycogen into glucose and triglycerides into fatty acids. Glucagon is the hormone of the hungry state.

419

How does insulin lower glucose?

Stimulates the uptake of glucose from blood to muscle and fat cells.
Activates the enzymes in the liver and muscles to make glucose into glycogen.

420

How does insulin promote glucose uptake into muscle and fat?

Causes glucose transporter proteins GLUT 4 to be inserted into plasmalemma of muscle and fat cells from intracellular stores.

421

What factors promote secretion of insulin?

Increased glucose, increased amino acids, increased parasympathetic activity and increased glucagon and GIP.

422

What factors inhibit the secretion of insulin?

Decreased glucose and increased sympathetic activity e.g. Exercise.

423

How can we test for DM?

We can do a oral glucose tolerance test.

424

What does a glucose tolerance test show?

Normally at an hour the amount of glucose in the blood decreases rapidly and is returned to normal more quickly than 2 hours.
In diabetes return to normal can take more than three hours.

425

What are some symptoms of DM?

Very high glucose, glycosuria, increased urinary volume, dehydration and consequently thirst.

426

How does diabetic ketoacidosis come about?

Inability of cells to utilise glucose causes a compensatory increase in lipolysis to generate fatty acids as an energy source.
Metabolism of fatty acids creates acetyl CoA.
Liver unable to process extra acetyl CoA through citric acid cycle and so ketone bodies are formed.

427

What does DKA result in?

Decreased pH and compensatory hyperventilation. Pear drop breath.

428

What stimulates glucagon release?

Decreased blood glucose.
Amino acids.
Sympathetic nerve activity.

429

What inhibits glucagon release?

Raised blood glucose and insulin.

430

How does glucagon raise blood glucose?

Increases liver glycogenesis.
Inhibits liver glycogen synthesis.
Promotes liver gluconeigenesis.
Promotes lipolysis in liver and adipose tissues.

431

What hormones controls glucose in the absorptive and post absorptive phases?

Insulin and glucagon.

432

What hormones controls glucose in emergencies?

Adrenaline from the adrenal gland.

433

What hormones controls glucose during starvation?

Cortisol from the adrenal gland and growth hormone from the pituitary gland.

434

How does glucagon prevent hypoglycaemia after a protein rich meal?

Insulin is released in response to amino acids which can result in hypoglycaemia by increasing glucose uptake by cells and reducing hepatic glucose output. But the meal has no glucose to replace the blood glucose lost.
Glucagon is released and it increases hepatic glucose output which causes hyperglycaemia and counteracts the insulin hypo.

435

How long can glycogen provide glucose for in the average adult?

Enough to provide glucose for 8 hours of starvation.

436

What happens if we still dont eat after glycogen runs out?

Fats are metabolised and proteins are catabolised.

437

In what part of the adrenal gland is aldosterone manufactured?

Zona glomerulosa.

438

In what part of the adrenal gland is cortisol manufactured?

Zone fasciculata.

439

In what part of the adrenal gland are the sex hormones manufactured?

Zone reticularis?

440

In what part of the adrenal gland is adrenaline manufactured?

In the storage granules of the medulla.

441

What kind of rhythm does cortisol secretion exhibit?

Diurnal rhythm. Higher while it's dark and lower in light.

442

What stimulates the adrenal gland to release adrenaline and cortisol?

Stress.

443

What does adrenaline do in relation to glucose?

Raises blood sugar.
Stimulates glycogenolysis.
Stimulates gluconeogenesis.
Released during short term emergencies.

444

What does cortisol do in relation to glucose?

Raises blood glucose.
Stimulates protein catabolism.
Stimulates gluconeogenesis.
Also stimulates lipolysis.
Isn't important for rapid mobilisation of fuel.

445

When does growth hormone become important in glucose control and what does it do? Where is it released from?

Released from anterior pituitary, becomes important in response to starvation.
Decreases glucose uptake by muscle.
Mobilises glucose from the liver.
Also promotes lipolysis in fat cells.

446

Where does excitation initiate in the heart?

The SA node.

447

What is sinus rhythm?

When the heart is being driven/controlled by the SA node.

448

What is the membrane potential of the SA node? What does this cause?

Have no stable resting membrane potential. This means they exhibit spontaneous pacemaker potential, which takes the membrane potential to a threshold that can generate an action potential in the SA node.

449

Where is the pacemaker potential seen on a graph of myocyte membrane potential?

It is the initial upstroke before the steep upstroke of action potential.

450

What is the permeability to potassium of pacemaker cells?

It is variable between action potentials.

451

What is the cardiac pacemaker potential?

The slow depolarisation of membrane potential to a threshold.

452

What causes cardiac pacemaker potential?

Decrease in potassium efflux superimposed on a slow sodium influx.

453

What are the two phases of cardiac action potential?

The rising phase and the falling phase.

454

What causes the rising phase (depolarisation) of action potential in the atria?

Activation of voltage gated calcium channels resulting in calcium influx.

455

What causes the falling phase (re polarisation) of action potential in the atria?

Activation of potassium channels resulting in potassium efflux.

456

What attaches cardiac cells to each other allowing spread of excitation?

Gap junctions and desmosomes with an intercalated disc in between.

457

Where is the AV node located?

At the base of the right atrium.

458

What delays conduction in the AV node?

AV node cells are small and have slow conduction velocity.

459

What is the resting membrane potential of the ventricular myocytes?

Is tire mains at a steady -90mv until the cell is excited.

460

What causes the rising phase of action potential in the ventricles?

Fast sodium influx, which rapidly reverses the membrane potential to +30mv.

461

What are the phases of ventricular muscle action potential numbered and what are they?

Phase 0 - fast na influx.
Phase 1 - closure or Na channels and transient K efflux.
2 - mainly ca influx.
3 - closure of ca channels and K efflux.
4 - resting membrane potential.

462

What is the plateau phase of ventricular action potential?

The membrane potential is maintained near peak for a very short time. It correlates to phase 2.
It is unique to cardiac contractile cells and is mainly due to calcium influx.

463

What causes the falling phase of action potential in the ventricles?

Inactivation of calcium channels and activation of k channels resulting in K efflux.

464

What is the relationship of the vagus nerve and the heart?

Exerts a continuous influence on the SA node under resting conditions. Vagal tone dominates under resting conditions. Slows the intrinsic HR from 100 to 70.

465

What should a normal resting HR be?

Between 60 and 100.

466

What anatomical sites in the heart does the vagus nerve supply?

The SA and AV nodes.

467

What does the vagal nerve do?

Slows HR and increases AV node delay.

468

What is the vagal nerves neurotransmitter and what receptor does it act on?

Acetylcholine and M2 receptors.

469

What is a competitive inhibitor of acetylcholine used for bradycardia?

Atropine.

470

What happens if the slope of pacemaker potential decreases?

HR slows as it takes longer to generate an action potential.

471

What does sympathetic stimulation of the heart do?
What is its transmitter?
What receptors does it work on?

Increase HR and decreases AV node delay.
Transmitter is norad.
Works on beta adrenoreceptors.

472

What does vagus stimulation do to the pacemaker potential slope?

Decreases the slope or makes it less steep.

473

What does norad stimulation do to the pacemaker potential slope?

Increases it or makes it steeper.

474

What is a chonotropic effect?

Frequency of action potential increases.

475

What do the gap junction in cardiac cells do in relation to the electrical current?

Form low electrical resistance electrical communication pathways.

476

What is the all or none law of the heart?

Gap junctions ensuring that electrical excitation reaches all the cardiac myocytes.

477

What do the desmosomes in heart cells do?

Provide mechanical adhesion between adjacent cells. They ensure that tension developed by one cell is transmitted to the next.

478

How thick are actin and myosin and what appearance do they have?

Actin are thin filaments, have lighter appearance.
Myosin are thick and cause the dark stripes.

479

What is it called when actin slides over myosin?

Sliding filament theory.

480

How does actin slide over myosin?

ATP dependent movement of cross bridges between the actin and myosin. The end of the cross bridge from the myosin is like a triangle at an angle, the triangle swings along binding sites on the actin moving it.

481

When is ATP required for movement of actin and myosin?

In both contraction and relaxation.

482

What do actin filaments look like?

Spirals of actin, wrapped in spirals of tropomyosin and troponin that the myosin cross bridges link to.

483

What ion is required to switch on cross bridging formation of actin and myosin?

Calcium.

484

Where is the sarcoplasmic reticulum in heart cells?

Is surround the muscle fibres.

485

Where is calcium released from and what is release dependent on during excitation contraction?

The sarcoplasmic reticulum. Release is dependent on presence of extracellular calcium.

486

What happens to the ions during the different phases ventricular muscle action potential?

Na influx during phase 0.
Calcium influx during phases 1 and two.
K efflux during 3 and 4.

487

What happens to calcium after cardiac action potential has ceased in the ventricles?

Calcium influx ceases and calcium is resequestered by SR. The heart muscle relaxes.

488

What happens to actin troponin during relaxation?

Cross bridge binding with myosin is not present as tropomyosin is covering the troponin.

489

What happens to actin troponin when the muscle is excited?

Calcium binds with it pulling it away from troponin- tropomyosin complex apart allowing cross bridging with myosin.

490

What is the cardiac refractory period?

Period following action potential when it's not possible to produce another action potential.

491

Why do we have a long refractory period?

It protects the heart as it means titanic contraction cannot take place.

492

What causes the cardiac refractory period?

During the plateau phase of ventricular systole the sodium channels are in the depolarised state and cannot be reopened. During the descending phase of action potential the potassium channels are open and the membrane cannot be depolarised.

493

What equation do we use to calculate stroke volume?

End diastolic volume - end systolic volume.

494

What is the intrinsic control of stroke volume?

Changes are brought about by changes in the diastolic length of myocardial fibres.

495

What determines the diastolic length of fibres in the heart?

The volume of blood in each ventricle at the end of diastole, otherwise known as end diastolic volume.

496

What determines the cardiac preload?

The end diastolic volume.

497

What determines the end diastolic volume?

Venous return to the heart.

498

What is the frank starling mechanism?

The relationship between venous return, end diastolic volume and stroke volume. It states...
The more the ventricle is filled with blood during diastole (EDV), the greater the volume of blood that will be ejected during the resulting systolic contraction (SV).

499

What does ventricular stretching do to calcium?

Increases the affinity of troponin for calcium.

500

How is optimal length in cardiac muscle achieved?

By stretching the muscle. Frank starling.

501

How does starlings law match the stroke volume of the right and left ventricles?

If venous return to RA increases Ventricular EDV increases, this causes an increased stroke volume to enter the pulmonary artery, causing increased preload from pulmonary vein on left side of heart. Hence increased SV or left side.

502

How does starlings law relate to the aorta?

It causes increased Stoke volume into it.

503

What can compensate for decreased SV due to increased afterload?

Frank starling mechanism.

504

What is the male for the effect that causes increased force of contraction in the heart?

Isotopic effect.

505

What is a chonotropic effect on the heart?

Increase of HR.

506

How does the sympathetic nervous system alter ventricular contraction?

Increases calcium influx by acting on the channels.causes a rise in the peak ventricular pressure. EDV rises and frank starling is more forceful.

507

What way does the frank starling curve shift in a, sympathetic stimulation and b, heart failure?

A to the left
B to the right.

508

What effect does vagus stimulation have on the force of contraction?

Very little. It controls rate more.

509

What hormones have chonotropic and intotropic effects on the heart?

Adrenaline and noradrenaline.

510

What is the volume of the resting cardiac output in a healthy adult?

Around 5l per min.

511

What is the volume of the resting stroke volume in a healthy adult?

70ml.

512

What are the 5 events during the cardiac cycle?

Passive filling,
atrial contraction,
isovolumetric ventricular contraction,
Ventricular ejection,
Isovolumetric ventricular relaxation.

513

What is the pressure in the atria and the ventricles?

Close to 0.

514

What is aortic pressure?

Around 80 mmHg.

515

How do the atria fill?

Passive filling.

516

How do the ventricles fill?

80% by passive filling. Then an average of another 130 ml form atrial contraction.

517

What is isovolumetric ventricular contraction?

The ventricles contract after QRS causing the ventricle pressure to rise. When ventricular pressure exceeds atrial the AV valve slams shut but the aortic valve is still shut. The tension around the closed volume is isovolumetric contraction. Cause a steep rise in ventricular pressure.

518

What causes the ESV and how much is it normally?

Stroke volume ejected from each ventricle when ventricular pressure exceed aortic and valve opens. What is left is the ESV. Usually 70 ml.

519

What causes the dicrotic notch in an aortic pressure curve?

The valve vibration of the aortic valve slamming shut.

520

What is isovolumetric ventricular relaxation?

Closure of aortic and pulmonary valves mean ventricles are closed boxes again. The tension falls around a closed volume = isovolumetric ventricular relaxation.

521

What are the normal heart sounds and what causes them?

S1 - closure of mitral and tricuspid.
S2 - closure of aortic and pulmonary valves.

522

What does S2 signify?

The end of systole and beginning of diastole.

523

What are the different parts of the jugular venous pressure wave?

First bump = atrial contraction.
Second bump = bulging of tricuspid into atria during ventricular systole.
Third bump = is the rise of atrial pressure during atrial filling.

524

What are the veins otherwise called and why?

Capitance vessels, as they contain most of the blood volume during rest.

525

What is resistance to blood flow directly proportional to?

The blood viscosity and the length of the blood vessel.

526

What is resistance to blood flow indirectly proportional to?

The radius of the blood vessel to the power of 4.

527

How is resistance to blood flow mainly controlled?

By vascular smooth muscle changing the radius of the arterioles.

528

What is the extrinsic control of vascular smooth muscle?
The neurotransmitter used?
What receptors does it act on?

Sympathetic nerve fibres.
Norad.
Alpha receptors.

529

What is vasomotor tone?

Blood vessel partially constricted at rest by sympathetic release of norad on alpha cells.

530

What is the effect of adrenaline on vascular smooth muscle?

Depends on predominant receptor type.
Alpha causes vasoconstriction.
Beta causes vasodilation.

531

Where are smooth muscle alpha receptors predominant?

Skin, gut and kidney arterioles.

532

Where are vascular smooth muscle beat cells predominant?

Cardiac and skeletal muscle.

533

What is intrinsic control of vascular smooth muscle?

Match the blood flow of different tissues to its metabolic needs. Can over ride extrinsic controls.
Include chemical and physical factors.

534

What local chemical metabolites cause intrinsic vasodilation?

Decreased local PO2 and increased PCO2.
Increased local H+ and increased extra cellular potassium.
Increased osmolarity of ECF.
Adenosine release for ATP.

535

What is NO, what releases it?

Nitric oxide, continuously released by arteries and arterioles em the,ail cells.

536

What is the effect of NO?

Potent vasodilator with a short life of a few seconds.

537

What can cause release of NO?

Always released from endothelial cells but shear flow causes release of calcium from endothelial cells and subsequent release of NO. Many vasoactive substances also cause it's release.

538

Where does NO diffuse to and what does this cause?

Adjacent smooth muscle cells, where it activates cGMP which also signals smooth muscle relaxation.

539

What is NO made from and what enzyme governs it?

L-arganine amino acid and nitric oxide synthase.

540

What is endothelin, what does it do and what stimulates its production?

A potent vasoconstrictor released from endothelial cells. Production stimulated by angiotensin II APand vasopressin.

541

What physical factors cause intrinsic control of vascular smooth muscles?
What do they cause?

Temp - heat = dilation. Cold = constriction.
Myotonic response to stress - when map rises resistance vessels automatically constrict to limit flow and vice versa.
Sheer stress - when vessels dilate the vessels downstream experience sheer stress and this makes them dilate. This increases blood flow to metabolically active tissues.

542

What is the result of increased venomotor tone?

Increased TPR, venous return, SV and MAP.

543

What blood pressure response do we have post exercise?

Hypotensive response due to increase in BP during exercise.

544

What are the 6 proposed CVS benefits of regular aerobic exercise?

Reduction in sympathetic tone and norad.
Increased parasympathetic tone to the heart.
Cardiac remodelling.
Reduction to plasma rennin levels.
Improved endothelial function.
Reduced arterial stiffening.

545

What is shock?

Abnormality of the circulatory system resulting in inadequate tissue perfusion and oxygenation.

546

What is the sequence of events going from shock to cellular failure?

Shock
Inadequate tissue perfusion
Inadequate tissue oxygenation
Anaerobic metabolism.
Accumulation of metabolic waste.
Cellular failure.

547

What is cardiogenic shock?

Sustained hypotension caused by decreased cardiac contractility.
Decreased contractility results in decreased stroke volume, resulting in decreased cardiac output, decreased Bp and inadequate tissue perfusion.

548

What are the steps in pneumothorax obstructive shock?

Increased intrathoracic pressure, causing decreased venous return, decreased EDV, decreased stroke volume, decreased CO and BPand therefore inadequate tissue perfusion.

549

What are the steps of neurogenic shock?

Loss of sympathetic tone, leading to massive venous and atrial dilatation, leads to decreased venous return and TPR, decreased CO and BP and inadequate perfusion.

550

What are the steps in vasoactive shock?

Release of vasoactive mediators, massive venous and atrial dilatation. Also increased capillary permeability, decreased venous return and TPR, decreased CO and BP and inadequate perfusion.

551

What is the treatment of shock?

ABCDE approach.
High flow oxygen and volume replacement.
Intotropes for cardiogenic shock
Chest drain for tension pneumo.
Adrenaline for anaphylaxis.
Vasopressors for septic shock.

552

What are the two main causes of hypovolamic shock?

Bleeding and water loss e.g. Vomiting, diarrhoea or excessive sweating.

553

What amount of blood can we lose and still have compensatory mechanisms maintain BP?

Up to 30%

554

How many classes of haemorrhagic shock do we have?

4. Divided by different blood loss volumes, HR, RR etc.

555

Where does the coronary sinus empty?

Into the right atrium.

556

What are the 3 special adaptations of the coronary circulation?

High capillary density.
High basal blood flow.
High O2 extraction 75%

557

What are the consequences of the high O2 extraction by coronary blood vessels?

Extra O2 cannot be supplied by increasing extraction. Need to increase coronary blood flow.

558

What intrinsic mechanisms control coronary artery blood flow?

Decreased PO2 causes vasodilation of coronary arteries.
Metabolic hyperaemia matches flow to demand.

559

What extrinsic mechanisms control coronary artery blood flow?

Coronary arteries are supplied by vasoconstrictor nerves but this is over ridden by metabolic hyperaemia cause by increased workload. This means sympathetic stimulation can cause vasodilation despite vasoconstrictor effect (functional sympatholysis)
Circulating adrenaline also activate beta adrenergic receptors which cause vasodilation.

560

What blood vessels supply the brain?

Internal carotids and vertebral arteries.

561

What is a special adaptation of the cerebral arteries that helps protect against hypoxia?

The circle of Willis. The arrangement means that if one of the main arteries or one carotid artery gets blocked, blood will still flow around the rest.

562

What are the two main types of stroke and how do they differ?

Haemorrhagic and ischaemia.
H- blood leaks out of a damaged artery.
I- blockage of artery causes decreased blood flow and tissue damage.

563

What is a special adaptation of cerebral blood flow which protects against loss of blood flow if map falls/rises?

Autoregulation. Disrespect sympathetic stimulation has very little affect on brain and do it doesn't vasoconstrict or dilate with the rest of the body.

564

What range of map can cerebral Autoregulation protect against?

60-160 mmHg

565

What happens to cerebral vessels when MAP rises?

Resistance vessels automatically constrict to limit blood flow.

566

What happens to cerebral vessels when MAP falls?

Cerebral arteries automatically dilate to maintain blood flow.

567

What gasses affect cerebral blood flow?

Increased PCO2 automatically causes cerebral vasodilation. Decreased PCO2 causes vasoconstriction which is why hyperventilation can lead to fainting.

568

What is normal ICP?

8-13 mmHg.

569

What is cerebral perfusion pressure, how do we calculate it?

CPP = MAP - ICP.

570

What can rising ICP do to cerebral blood flow?

decreases CPP and blood flow and can lead to failure of Autoregulation of cerebral blood flow.

571

What forms the blood brain barrier?

Cerebral capillaries have very tight intercellular junctions. O2 and CO2 are highly permeable, glucose transferred by facilitated diffusion. It is impermeable to hydrophilic substances such as ions and proteins etc. helps protect from fluctuating ion levels in the brain.

572

What is a typical pulmonary artery BP?

Usually 10% of systemic circulation.

573

What is pulmonary capillary BP?

Usually around 8-11mmhg.

574

What is systemic capillary pressure?

Roughly 17-25mmHg.

575

What does hypoxia do to pulmonary arterioles?

Causes vasoconstriction. This is opposite from the rest of the body. It allows blood to be diverted from poorly ventilated areas of the lung.

576

What causes vasodilation on skeletal muscles?

Adrenaline working on beta 2 adrenergic receptors.

577

Why don't varicose veins lead to a reaction of cardiac output?

Because of chronic compensatory increase in blood volume.

578

What regulates blood flow to capillary beds other than sphincters?

Terminal arterioles in most tissues. Precapillary sphincters only regulates blood flow in a few tissues like the mesentery.

579

How do gasses, fluid, lipophilic, hydrophilic and large molecules cross the capillary wall?

Fluid - pressure gradient for bulk flow.
Gasses - Ficks law of diffusion.
Lipophilic - go through endothelial cells.
Hydrophilic - water filled pores.
Large molecules - do not generally pass across the wall.

580

What is net filtration pressure?

Made up of forces favouring filtration and forces opposing filtration. A filtration coefficient also effects net fluid filtration.

581

What two forces favour filtration?

Capillary hydrostatic pressure and interstitial fluid osmotic pressure.

582

What two forces oppose filtration?

Capillary osmotic pressure and interstitial fluid hydrostatic pressure.

583

What are the forces involved in transcapillary flow called?

Starling forces.

584

What ends of venules do starling forces favour filtration and reabsorption at?

Filtration at the arteriolar end as NFP = +10.
Reabsorption at venular end as NFP = -8.
This example is of skeletal muscle.

585

What is greater during an average day, capillary fed filtration and reabsorption?

Filtration by about 2-4 litres. Excess drained by lymphatics.

586

What is oedema and what is its consequence on gas exchange?

Fluid in the interstitial space. Diffusion distance causes impaired gas exchange.

587

What four categories of change can cause oedema?

Raised capillary pressure, reduced plasma osmotic pressure, lymphatic insufficency and changes in capillary permeability.

588

What can cause raised capillary pressure?

Anterior dilatation or raised venous pressure.

589

What are three causes of raised venous pressure and what kind of oedema do they cause?

LVF - pulmonary oedema.
RVF peripheral oedema - ankle or sacral.
Prolonged standing - swollen ankles.

590

What is normal plasma protein levels?

65-80g/L

591

What plasma protein level can cause oedema?

Under 30 g/L.

592

What can cause reduced plasma osmotic pressure leading to oedema?

Malnutrition, protein malabsorption, excessive renal excretion of protein and hepatic failure.

593

What is internal respiration?

Intracellular mechanisms that consume O2 and release CO2.

594

What is external respiration?

Sequence of steps that lead to exchange of gasses in the environment and the body cells.

595

What are the four steps of external respiration?

Ventilation - gas exchange between the atmosphere and the air sacs.
Exchange of gasses between alveoli and the blood.
Transport in the blood between the lungs and the tissues.
Gas exchange at the tissue level. Between blood and body cells.

596

What is Bowles law?

At a constant temperature, the pressure exerted by a gas varies inversely with the volume of the gas.

597

How does lung ventilation work?

Air flowing down a pressure gradient due to intrathoracic pressure changes.

598

What three pressures are important in ventilation?

Atmospheric, intra alveolar and intrapleural.

599

What is the normal environmental and intra alveolar pressure?
What is the normal intrapleural pressure?

760
756.

600

What two forces hold the lungs and thoracic wall in close opposition?

The intrapleural fluid cohesiveness - water molecules are attracted to each other and resist being pulled apart.
The negative intrapleural pressure - causes a transmittal pressure gradient across the lung wall, forcing lung to expand out while chest squeezes inwards.

601

What is inspiration?

Active process depending on muscle contraction of inspiratory muscles. Chest wall and lungs stretch causing gas to rush in due to boyles law.

602

What do intra alveolar and intrapleural pressures fall to during inspiration?

759 and 754.

603

What do intra alveolar and intrapleural pressures rise to during expiration?

761 and 756

604

What nerves cause the diaphragm to move during respiration?

Phrenic nerves from cervical 3,4 and 5.

605

What muscles lift the ribs during inspiration?

The external intercostal.

606

What happens to the sternum during inspiration?

It is forced to move upwards and outwards by the ribs causing increased depth of thoracic cavity.

607

What causes lungs to recoil during expiration?

Elastic lung recoil and alveolar surface tension.

608

What is the alveolar surface tension?

Attraction between water molecules at liquid air interface. Produces a force that prevents stretching of the lung.surfactant reduces the surface tension, as water alone would have too much attraction and the alveoli would collapse.

609

What is the law of Laplace?

Smaller alveoli have a higher tendency to collapse. Surfactant lowers the surface tension of smaller alveoli more than large alveoli. This prevents the smaller ones collapsing and dispersing contents into big ones.

610

What is pulmonary surfactant a mix of?

Lipids and proteins amongst the water.

611

What secretes pulmonary surfactant?

Type 2 alveoli.

612

What is respiratory distress of the new born?

Lungs can't make surfactant until later in pregnancy so when born the baby has to make strenuous effort to inflate alveoli.

613

What is alveolar interdependence?

If alveoli start to collapse the the surrounding ones are stretched and recoil, exerting expanding forces on the one collapsing.

614

What three forces keep alveoli open? Start with the most important.

Transmural pressure gradient, pulmonary surfactant and alveolar interdependence.

615

What three forces promote alveolar collapse? Start with the most important.

Elasticity of stretched pulmonary connective tissue fibres.
Alveolar surface tension.

616

What are the accessory muscles of inspiration?

Sternocleidomastoid and scalenus.

617

What are the major muscles of inspiration?

External intercostal muscles and the diaphragm.

618

What are the muscles of active/forced expiration?

Internal intercostal muscles and the abdominal muscles.

619

What can cause a variation in predicted normal spirometry values?

Age, height, sex etc.

620

What is spirometry and what can it show us?

Test used to find dynamic lung volumes.
We can determine:
FVC - the max forced from the lungs after maximum inspiration.
FEV1 and the FEV p1 percentage e.g. The FeV1: FVC ration

621

What is tidal volume?

Volume entering and leaving in one breath. Usually 500 ml.

622

What is the inspiratory reserve volume?

Extra volume of air that can be forcefully inspired over normal TV e.g. Normal expiration. Is usually 3000mls.

623

What is the inspiratory capacity?

Maximum volume of air that can be inspired after a normal quiet inspiration e.g. IRV + TV. Normally 3500.

624

What is the expiratory reserve volume?

Extra volume that can be maximally expired beyond the normal air after a resting tidal volume. E.g. Breath out normally and then blow. Usually about 1000mls.

625

What is residual volume?

Minimum volume of air left in the lungs after a maximal expiration. Usually 1200mls.

626

What is the functional residual capacity?

Volume of air in the lungs after normal passive expiration. ERV + RV. Normally 2200mls.

627

What is the vital capacity?

Max volume of air that can be moved out with a single breath following maximal inspiration. Is IRV + TV + ERV. Usually 4500mls.

628

What is the total lung capacity?

Max volume of air that the lungs can hold. Is VC + RV. Usually around 5700mls.

629

What is forced expiratory volume is 1 second?

FEV1 volume of air expired during the first second of expiration in an FVC determination.

630

What is a normal FEV1 percentage?

Greater than 75%

631

What is the FVC, the FEV1 and the FEV1/FVC% in an airway obstruction?

FVC - low or normal.
FEV1 - low
FEV1/FVC% - low.

632

What is the FVC, the FEV1 and the FEV1/FVC% in an airway restriction?

FVC - low
FEV1 - low
FEV1/FVC% - normal.

633

What is the FVC, the FEV1 and the FEV1/FVC% in an airway obstruction/restriction?

FVC - low
FEV1 - low
FEV1/FVC% - low

634

What is the primary determinant of airway resistance?

Radius of the conducting airway.

635

What happens to the airways during inspiration?

They are pulled open by thorax expansion.

636

What happens to the airways during expiration?

Dynamic airway compression due to rising pleural pressure. Rising pressure compresses the alveoli and helps push the air out. Pressure applied to the airway can compress it and is fine in healthy people but can cause problems in sick people. The increased airway pressure means the alveoli are more likely to stay open as there is increased pressure downstream from the airway.

637

What happens to airway driving pressure if there is an obstruction?

Driving pressure is lost over obstructed segment, causing loss in airway pressure downstream. Means airways are more likely to collapse during expiration.

638

What is pulmonary compliance?

Is the measure of the effort that has to be put into stretching or dispensing the lungs during inspiration.

639

What are some examples of diseases causing decreased pulmonary compliance?

Pulmonary fibrosis, oedema, pneumonia and absence of surfactant.

640

What does decreased pulmonary compliance mean for respiratory rate?

Greater pressure is needed to produce a volume change. Causes shortness of breath.

641

What can decreased pulmonary compliance look like on spirometry?

May look like a restrictive pattern.

642

What is and what can cause increased pulmonary compliance?

Elastic recoil of the lung is lost. Emphysema can cause it. Causes hyperinflation of the lungs and more work is required to get air out the lungs. Age also increases compliance.

643

How full are lungs normally?

About half full.

644

What situations can increase the work of breathing?

Decreased pulmonary compliance.
Increased airway resistance.
Decreased elastic recoil.
Need for increased ventilation.

645

What is anatomical dead space and how much is it usually?

Air remaining in the airways where it is not available for gas exchange. Usually about 150mls.

646

What is pulmonary ventilation and how is it calculated?

The amount of air going in and out in a minute. Calculated by RR x TV.

647

What is alveolar ventilation like compared to pulmonary ventilation? How do we calculate it?

Less due to anatomical dead space. It is the volume of air exchanged between the air and alveoli per minute.
= tidal volume- dead space multiplied by respiratory rate.

648

What two ways can we increase pulmonary ventilation during exercise and which is more effective?

Increase depth- TV and RR.
TV more effective due to anatomical dead space.

649

What is VQ and what do they mean?

Ventilation - the rate at which gas is passing through the lungs.
Perfusion - the rate at which blood is passing through the lungs.

650

What happens to VQ in different areas of the lung?

They vary from top to bottom.

651

What is alveolar dead space?

The match between air in alveoli and blood in capillaries isn't always equal. Therefore alveoli that are not perfumed are considered dead space.

652

What is the physiological dead space?

Anatomical dead space plus the alveolar dead space.

653

How is VQ matched in the lungs?

Local control of the smooth muscle in airways and arterioles try and match them.
Accumulation of CO2 in the alveoli due to increased perfusion causes decreased airway resistance and so increased airflow.
Increase in alveolar O2 causes vasodilation allowing increased blood flow.

654

What four factors influence the rate of gas exchange across the alveolar membrane?

Partial pressure gradients of gasses.
Diffusion coefficient of gasses.
Surface area of alveolar membranes.
Thickness of alveolar membrane.

655

What is Dalton's law?

The total pressure exerted by a gas mixture is equal to the sum of partial pressures of each gas.

656

How can we work out the partial pressure for a gas?

Gasses exert the same pressure as part of a mixture of gasses as they would if it were only that gas present. Therefore if half a mixture is made of a gas the partial pressure of the gas is 50kPa.

657

What is the partial pressure of O2?

160mmhg.

658

What is the alveolar gas equation and what do the parts mean?

PAO2 = PiO2 - (PaO2/0.8)
PAO2 is the partial pressure of O2 in alveolar air.
PiO2 is the partial pressure of O2 in inspired air.
PaCO2 is the partial pressure of CO2 in arterial blood.

659

What is the respiratory exchange ration and what is it for CO2 and O2.

The ratio of CO2 produced /O2 consumed for someone that is eating a normal diet.

660

How do we convert mmHg to kPa?

Divide mmHg by 7.5

661

What is the O2 pressure gradient from alveoli to blood and from blood to tissue cells?

60 mmHg or 8 kPa. The same

662

What is the CO2 pressure gradient from blood to alveoli and from tissue cells to blood?

6mmhg or 0.8 kPa.

663

What is the diffusion coefficient of a gas?

The solubility of a gas in a membrane.

664

What does a big gradient between alveolar PO2 and arterial Po2 indicate?

Problems with gas exchange in the lungs or right to left shunt in the heart.

665

What is shortened simplified way to say Ficks law of diffusion?

The amount of gas that moves across a sheet of tissue is proportional to the are of the sheet but inversely proportional to its thickness.

666

What structure is between the bronchioles and the alveolar sacs?

The alveolar ducts.

667

What is Henry's law?

The amount of gas dissolved in a given type and volume of liquid, at a given temperature is proportional to the partial pressure of the gas in equilibrium with the liquid.
This means that if the partial pressure of a gas is increased, the gas in the liquid would increase proportionately.

668

What is normal concentration of O2 in the blood?

Around 20% e.g. 200ml per litre.

669

How much O2 in the blood is carried by Hb?

Around 98.5% the rest is dissolved in the blood.

670

What is the primary factor affecting the percentage saturation of Hb O2?

The PO2.

671

What is Hb cooperativity?

Binding of one O2 increases the affinity of Hb for O2.

672

What shape is the oxygen dissociation curve?

Sigmoid.

673

What is a Hb molecule comprised of?

An alpha chain, a beta chain and four haem groups.

674

Where is myoglobin and how many haem does it contain?

In skeletal muscle and cardiac muscles. Contains 1 haem group.

675

What shape is the myoglobin dissociation curve? What is the significance of this?

Hyperbolic. It means myoglobin only releases O2 at very low PO2 levels and so provides a small store of O2 for anaerobic conditions.

676

What does presence of myoglobin in the blood indicate?

Muscle damage.

677

How is CO2 transported in the blood?

10% in solution, 60% as bicarbonate and 30% as carbamino compounds.

678

How much more soluble is CO2 than O2?

20 times.

679

What is the equation for transport of CO2 in the blood?

CO2 + H2O H2CO3 H+ + HCO-3.

680

What are carbamino compounds?

Combination of CO2 with terminal amine groups of blood proteins.

681

What is the Hakodate effect in relation to CO2?

Removing O2 from Hb increases the ability of Hb to pick up Co2 and H+. This works to allow respiration at tissue levels.

682

What is the major rhythm generator for respiration?

The medulla.

683

What group of cells regulate breathing rhythm and where are they?

Pre-botzinger complex in the upper end of the medulla respiratory centre. They exhibit pacemaker activity.

684

What do the dorsal respiratory neurones in the medulla do?

Fire in burst, leading to contraction of inspiratory muscles. When firing stops passive expiration happens.

685

What does increased firing of dorsal respiratory neurones lead to?

Excites the ventral group neurones. These excite the internal intercostals and abdominals etc. causing forced expiration. E.g. During hyperventilation.

686

What can alter the respiratory rhythm generated in the medulla?

The pneumotaxic centre in the pons.

687

What happens when the pneumotaxic centre is stimulated? What stimulates it?

It terminates inspiration. Stimulated when the dorsal respiratory neurones fire.

688

What would happen to breathing without the pneumotaxic centre?

Breathing is prolonged inspiratory gasps with only brief expiration.

689

What does the apneustic centre do when it is stimulated?

It excites the inspiratory area of the medulla causing prolonged inspiration.

690

What stimuli can influence the respiratory centres in the brain?

Hering bruer reflex, baroreceptors, chemoreceptors, juxtapulmonary (j) receptors and higher brain centres.

691

What is the juxtapulmonary receptors stimulated by?

Pulmonary capillary congestion, pulmonary emboli and pulmonary oedema.

692

What is the hering-bruer reflex?

When pulmonary stretch receptors are activated during inspiration, afferents discharges inhibit inspiration. Only activated at large e.g. Over a litre tidal volumes. May prevent over inflation of the lungs during exercise.

693

How do joint receptors alter breathing?

Impulses from moving limbs reflex ell increase breathing.

694

What exercise factors alter breathing?

Joint movement, adrenaline release, increase in temp and accumulation of CO2 and H+ generated by active muscles.

695

How does the cough reflex effect breathing?

Irritation of airways causes a short intake of breath followed by closure of the larynx, then contraction of the abdominal muscles and finally opening of the larynx and expulsion of air at high speeds.

696

What is chemical control of breathing and what sensors are used?

Negative feedback of gas levels in blood, especially CO2. Sensed by chemoreceptors.

697

Where are central chemoreceptors situated? What triggers them?

Near the surface of the medulla in the brainstem. H+ content of csf.

698

Why is CSF less buffered than blood?

It contains less proteins.

699

What is the hypoxia drive of respiration?

Chemoreceptors are stimulated when PO2 falls below 8kPa. Not important in normal respiration but may be in COPD patients with CO2 retention.

700

What do we get hypoxia at high altitudes?

The pO2 is low.

701

What are some symptoms of mountain sickness?

Headache, fatigue, nausea, tachycardia, dizziness etc.

702

What are some adaptations to chronic hypoxia?

Polycythaemia (RbC) formation.
O2 offloaded more easily into tissues.
Increased capillary number.
Differing number of mitochondria.
Kidneys conserve acid, lowering arterial pH.

703

What is the H+ drive of respiration?

Via peripheral chemoreceptors, stimulation causes hyperventilation and increases CO2 elimination.