GB lectures Flashcards
1
Q
Site of production of gastrin
A
g cells in antrum of the stomach
2
Q
what receptor does gastrin bind to
A
CCK2 in the stomach but can also bind to CCK1 in the gallbladder
3
Q
effect of gastrin binding to its receptor
A
binding with CCK2 increases acid production and mucosa thickening
4
Q
what stimulates gastrin release
A
cephalic and gastric phase - vagovagal stimulation and distension caused by bolus of food
intestinal phase - by digested amino acids
5
Q
what are the overall effects of gastrin release
A
stimulates mucosa proliferation increases gastric acid release increased growth of stomach mucosa increased splanchnic blood flow causes the release of histamine
6
Q
what hormone causes the release of histamine
A
gastrin
7
Q
where is histamine released from
A
enterochromaffin- like cells
8
Q
what stimulates the release of histamine
A
gastrin
9
Q
effects of histamine
A
vasodilation
increased acid secretion
10
Q
Site of production of CCK
A
I cells in the upper intestine (duodenum and jej.)
11
Q
what receptor does CCK bind to
A
CCK1 in the gallbladder but can also bind to CCK2 in the stomach
12
Q
effect of CCK binding to its receptor
A
causes the release of somatostatin from Delta cells
13
Q
what stimulates CCK release
A
triggered by amino acids and peptides and monoglycerides and fatty acids
it is also activated by sensory afferents or by itself
14
Q
what are the overall effects of CCK release
A
bind to CCK1 to inhibit acid secretion
bind to CCK2 to increase acid secretion
increases splanchnic blood flow
15
Q
Site of production of secretin
A
S cells in the duodenum
16
Q
Secretin has a similar structure to what other substances?
A
secretin is a peptide similar to VIP and glucagon
17
Q
what stimulates secretin release
A
in response to acidic chyme of the stomach entering the duodenum
trigger - low pH and fatty acids
secretin- releasing- peptide activated by sensory afferents
18
Q
what are the overall effects of secretin release
A
induces exocrine secretions from gallbladder and pancreas
stimulates insulin release form pancreas
decreases acid secretion via the release of somatostatin
decreases gastric motility via vagal reflex
increases blood flow
19
Q
Site of production of somatostatin
A
produced by delta cells in the pancreas and stomach
20
Q
what stimulates somatostatin release
A
triggered by CCK , ACh
increased blood glucose and amino acids (after eating)
21
Q
what are the overall effects of somatostatin release
A
inhibitory effects
decreases acid production
decreases motility
decreases blood flow
22
Q
motilin release
A
released every 90 minutes
23
Q
what inhibits motilin release?
A
food in the stomach
24
Q
Site of motilin release
A
mucosa of upper GI
25
what are the overall effects of motilin release
migrating motor complex (rumbling) which clears foreign bodies from GI tract
26
importance of migrating motor complex
clears foreign bodies from GI tract
27
Site of gastric inhibitory peptide release
k cells in the duodenum and jejunum
28
what stimulates gastric inhibitory peptide release
presence of food in the upper small intestine
29
what are the overall effects of gastric inhibitory peptide release
inhibits gastric secretions and motility
| induces insulin secretion
30
Site of serotonin release
enterochromaffin cells
31
what stimulates serotonin release
vomitting
32
what is the role of antiemetics
antiemetics block 5-HT3 (serotonin receptor) on sensory afferent fibres (ondansetron)
33
what is the serotonin receptor
5-HT3
34
g cells in antrum of the stomach produce...
gastrin
35
why can gastrin and CCK bind to the same receptors
gastrin and CCK are structurally related peptides that share the same C terminal
36
what hormone binds with CCK2 and increases acid production and mucosa thickening
gastrin
37
```
what hormone(s) do the following action:
increased splanchnic blood flow
```
gastrin
CCK
secretin
38
what hormone does the following action:
| stimulates mucosa proliferation
gastrin
39
what hormone causes the release of histamine
gastrin
40
what hormone does the following action:
| increased growth of stomach mucosa
gastrin
41
```
what hormone(s) or substance(s) do the following action:
increase gastric acid secretions
```
gastrin
| histamine
42
what hormone does the following action:
| inhibit acid secretion
secretin
CCK
GIP
43
what hormones do the following action:
| decreases motility
```
secretin
GIP (no effect on intestinal motility)
```
44
what hormone does the following action:
| decreases blood flow
somatostatin
45
what hormones do the following action:
| increase motility
gastrin
CCK
motilin
46
what hormones cause insulin release in the GI tract
gastrin
CCK
secretin
GIP
47
the binding of hormones to CCK1 and CCK2 induce different effects. what are the effects per receptor
bind to CCK1 to inhibit acid secretion
| bind to CCK2 to increase acid secretion
48
I cells in the upper tract produce...
CCK
49
S cells in the duodenum produce
secretin
50
delta cells in the pancreas produce
somatostatin
51
mucosa cells in the upper GI tract release...
motilin
52
k cells in the duodenum and jejunum produce
GIP - gastric inhibitory peptide
53
enterochromaffin cells release
serotonin
54
enterochromaffin-like cells release
histamine
55
Ondansetron
anti-emetic
56
what hormones induce pancreatic secretions
gastrin
CCK
secretin
GIP
57
which hormones are triggered by acid release
CCK
secretin
motilin
58
which hormone is triggered by carbohydrate release
GIP
59
which hormone is triggered by fat release
CCK
secretin
GIP
motilin
60
which hormone is triggered by protein release
gastrin
CCK
GIP
61
which hormones have a nervous stimuli
gastrin
| motilin
62
which hormones are stimulated by distension
gastrin
63
what releases GIT peptides?
enteroendocrine cells distributed throughout mucosa (NOT IN GLANDS)
64
major site for GI peptide release
duodenum
| jejunum
65
what are the conditionally essential amino acids
arginine
glutamine
tyrosine
66
what is a conditionally essential amino acid
aa that cannot be synthesised in sufficient quantities during growth and recovery
67
macrominerals intake value per day and examples
Ca and P
| 100mg/day
68
microminerals intake value per day and examples
Fe and Zn
| < 100mg/day
69
how is a micromineral deficiency altered?
reversible by ingestion
70
BMR value
24kcal/day
71
what factors cause an increase in BMR
increased in males, children, hyperthyroidism and fever
72
what factors cause a decrease in BMR
decreased in females, hypothyroidism and in starvation
73
DIT
diet induced thermogenesis
thermic effect of food
10% of BMR
74
10% of BMR
DIT
75
thermic effect of food
DIT
76
Estimated average requirement
intake at which inadequacy is 50%
77
Recommended Dietary Allowance
intake at which risk is 2-3%
78
Adequate intake
range of healthy intake
79
upper limit
excessive amounts above this lead to excessive risk
80
intake at which inadequacy is 50%
Estimated average requirement
81
intake at which risk is 2-3%
Recommended Dietary Allowance
82
range of healthy intake
Adequate intake
83
excessive amounts above this lead to excessive risk
upper limit
84
total parenteral nutrition
IV --> H2O, glucose, AA, vitamins, salts
85
what is secondary malnutrition. give examples
this is a condition that prevents proper digestion/ absorption (loss of appetite, fever, infection, diarrhea, parasites)
86
what is micronutrient malnutrition
deficiency or too much of a vitamin/mineral
87
what is protein energy metabolism. give examples
underconsumption of calories or protein
marasmus - calorie deficiency
kwashiorkor - protein deficiency
88
marasmus
calorie deficiency
89
kwashiorkor
protein deficiency
90
calorie deficiency
marasmus
91
protein deficiency
kwashiorkor
92
dysphagia
difficulty swallowing
93
difficulty swallowing
dysphagia
94
name the salivary glands and describe their secretions
parotid - watery, serous, contains amylase
sublingual - mucous
submandibular - mixed serous and mucous, mucin, amylose
95
what gland(s) produce(s) mucous secretions?
sublingual
| ** submandibular - mixed
96
mucin
glycoprotein that maintains homeostasis of epithelia
97
contents of saliva
```
mucins
alpha amylase
lingual lipase
Ig A
lysozymes
```
98
compare saliva to ECF
saliva
less Na Cl
more K HCO3-
99
saliva production per day
1 L
100
compare and contrast the sympathetic and parasympathetic innervation of the salivary glands
both increase secretion
sympathetics constrict the vessels --> less blood flow --> less secretions
** they both allow for secretion but the parasympathetics allow for more
101
Xerostomia
dry mouth induced by stress
102
what are the layers of gut tube
lamina - mucosa - submucosa - meissner's plexus - inner circular muscle - auerbach's plexus - outer longitudinal muscle - serosa
103
submucosal plexus
meissner's plexus
104
myenteric plexus
meissner's plexus
| auerbach's plexus
105
muscularis externa
inner circular muscle
| outer longitudinal muscle
106
where do the afferents of the intrinsic regulation of the gut go to
both the CNS for ANS regulation
| Intramural plexus for intrinsic regulation
107
explain the phases of swallowing
```
oral phase (voluntary)
Pharyngeal phase (reflex) - soft palate rises, epiglottis covers larynx, relaxation of the UES, constriction of the superior pharyngeal constrictor
esophageal phase (reflex) - primary peristaltic waves move food down and secondary waves clear the esophagus
```
108
name of reflex in swallowing
vagovagal reflex
109
nerves involved in pharyngeal phase of swallowing
CN V, VII, IX, X XII
110
nerves involved in secretion of saliva
CN VII, IX
111
describe the structure of the esophagus
divided into thirds
first - striated muscle
middle - striated and smooth muscle
last - smooth muscle
112
LES description, innervation and activity
physiological sphincter
always active
maintained by parasympathetics of X
vagal cholinergic activity
113
action of LES
relaxes ahead of peristalsis due to vagal stimulation through the release of VIP and NO
114
what is the effect of ACh, VIP and NO on the LES
active - contracts - ACh
| inactive - relaxes - VIP and NO (INHIBITS CONTRACTION)
115
explain the process of vomiting
afferent X --> medulla (vomiting centre) --> V, VII, IX, X, XII efferents
116
where does the stimuli of vomiting enter the medulla and give examples of stimuli
enter medulla through the chemoreceptor trigger zone (bypassing the BBB)
eg. drugs, opioids, anesthesia
117
Muller's Manoeuvre
forced inspiration against a closed glottis
118
Intrinsic control of the GI tract is done by the...
Enteric NS
119
How many neuron types are in the ENS and what are they?
```
3
sensory (from mucosa) --> interneurons- --> motor neurons (control motility and secretions of smooth muscle and endo/exocrine cells)
```
120
function of motor neurons of the ENS
control motility and secretions of smooth muscle and endo/exocrine cells
121
plexuses of the ENS and their fxns
meissner's plexus - secretion of mucosa
| auerbach's plexus - motor function of smooth muscle
122
what do excitatory fibres of the ENS release?
ACh
123
what do inhibitory fibres of the ENS release?
VIP and NO
124
Extrinsic control of the GI tract is done by the...
ANS
125
describe the sympathetic and parasympathetic innervation in the ANS
symp - arise from prevertebral ganglion --> releases noradrenaline
parasympathetics - arise from vagus nerve (upper GI) and the pelvic nerve (lower GI) - release Ach
126
what triggers the waves of smooth muscle contraction
cells of cajal
127
where are the cells of cajal located
between the circular and longitudinal muscles
128
describe the waves of smooth muscle contraction
initied cycles of EPSPs that do not reach the threshold of the AP
occurs along length of GI tract
fastest - duodenum
slowest - colon
129
regions of the stomach
secretory - fundus, body, antrum
motility - orad (proximal), caudad (distal)
the pacemaker region is divided in the 2 part
130
receptive relaxation
it is the vagovagal reflex of the lower esophagus and proximal stomach (orad) when swallowing
this reflex allows for an increase in volume without increasing pressure
131
Mixing in the stomach
controlled by mechanical stimuli
stomach distention --> gastric release
Ach release by vagus
gastrin is inhibited by secretin
132
describe the gastric phases
1) Cephalic
triggered by sight, smell or thought of food
release of gastrin, mucus, HCl and pepsinogen
stimulated by vagovagal and GRP (gastric releasing peptide)
2) gastric
stretch or distension of the stomach leads to an increase in the release of gastrin
stimulates mixing and emptying as well as HCO3- buffering
3) intestinal
release of CCK and secretin as receptors of the duodenum activate
amino acids entering stimulate the release of gastrin§
133
gastric glands and what they produce
1) surface epithelial cells - secrete thick mucus with mucin and HCO3- ; lubricates and protects against lower pH and enzymes
2) pyloric glands - located in antrum; g cells release gastrin; d cells release somatostatin (endocrine and paracrine)
3) oxyntic/ parietal cells secrete Hcl and intrinsic factor for B12 absorption
4) peptic or chief cells - secrete pepsinogen
5) enterochromaffin-like cells - secrete histamine (paracrine secretion)
6) mucous neck cells - thin mucus
134
what inhibits gastrin release
low pH through negative feedback
135
relationship of acid secretion and blood flow
acid secretion is proportional blood flow
136
process of acid secretion by oxyntic/ parietal cells
1) carbonic anhydrase : CO2 + H2O --> H2CO3 --> HCO3- + H+
2) Cl-/HCO3- exchanger releases HCO3- into the blood and Cl- into the stomach lumen
3) H+/K+ ATPase brings K+ into the cell and releases H+ into lumen --> H+ + Cl- --> HCl
137
what stimulates acid secretion
histamine
138
what inhibits acid secretion
somatostatin and PGE2
139
in acid secretion, Histamine uses a _____ receptor with the second messenger ____ which boosts _____ activity.
GPCR
cAMP
H+/K+ ATPase
140
Inhibitors such as somatostatin and PGE2 work by...
inhibiting the cyclisation of cAMP
| H+/K+ ATPase stops working and there is no release of H+ into the lumen
141
in acid secretion, Ach and gastrin uses _____ which boosts _____ activity.
PLA and IP3
142
which pathway in acid secretion of the oxyntic cell is not inhibited by somatostatin and PGE2?
Ach and gastrin
143
CO2 + H2O --> H2CO3 enzyme
carbonic anhydrase
144
Cl-/HCO3- exchanger releases HCO3- into the _____ and Cl- into the _____.
blood
| stomach lumen
145
H+/K+ ATPase brings __ into the cell and releases __ into lumen
K+
| H+
146
too much acid secretion can cause ----
gastritis or inflammation of gastric mucosa
147
gastritis or inflammation of gastric mucosa caused by...
too much acid secretion
| too little mucus secretion
148
_(bacteria)__ causes infiltration of leukocytes causing inflammation and increases acid secretion
helicobacter pylori
149
what do anti inflammatory medications act on inthe acid secretion pathway. example of drug
eg aspirin, ibuprofen
| decreases the prostaglandins and increase acid secretion
150
structural adaptations of the stomach
- tight junctions
- lack of villi
only lipid soluble substances and alcohol are absorbed here
151
composition of exocrine secretions of pancreas
1) aqueous component - mainly Na+ and HCO3- secreted by ductal epithelial cells
2) enzymatic component - mainly inactive precursors secreted by acinar cells
152
what pancreatic secretions are stimulated by the cephalic and gastric phases
vagal Ach stimulates both Acinar and ductal secretions
153
what hormones are involved in the intestinal phase and what is their action
1) secretin - stimulated by acid in duodenum and stimulates ductal cells to secrete HCO3- to buffer acids and Na+
2) CCK - stimulated by fat and AA in duodenum and stimulates acinar cells indirectly through vagal afferents
154
aqueous component of pancreatic secretions
mainly Na+ and HCO3- secreted by ductal epithelial cells
155
what do ductal epithelial cells secrete
Na+ and HCO3-
156
enzymatic component of pancreatic secretions
mainly inactive precursors secreted by acinar cells
157
what do acinar cells secrete
inactive precursors
158
what hormone stimulates ductal epithelial cells
secretin in the intestinal phase
159
what hormone stimulates acinar cells
CCK in the intestinal phase
160
bile is secreted by ....
hepatocytes
161
bile is stored in the...
gall bladder
162
bile is composed of
bilirubin, cholesterol, bile salts, other fats
163
how does CCK affect the gallbladder
CCK acts on CCK1 to constrict the gallbladder and secrete bile through the sphincter of oddi
164
brunner's gland
located in the early duodenum and secrete mucus and HCO3- to protect af=against acidic secretion.
165
what stimulates the brunner's gland
distention and PNS
166
regulation of food intake is done by the ...
hypothalamus
167
inhibitory pathway of regulation of food intake
POMC (pro-opiomelanocortin pathway)
POMC containing neurons release alpha melanocyte-stimulating hormone (alpha MSH) which stimulates metabolism
the vagus nerve (X) or PNS induces satiety --> inhibits feeding
168
stimulatory pathway of regulation of food intake
orexigenic pathway involves neuropeptide Y which stimulates food intake and inhibits metabolism --> induces hunger
169
insulin site of production
beta cells of the pancreas
170
how does insulin affect the regulation of food intake?
induces feeling of satiety following a meal
171
orexigenic pathway
inhibits metabolism --> induces hunger
172
POMC (pro-opiomelanocortin pathway)
induces satiety --> inhibits feeding
173
inhibitory pathway of regulation of food intake -POMC containing neurons release _______ which stimulates metabolism
alpha melanocyte-stimulating hormone (alpha MSH)
174
stimulatory pathway of regulation of food intake -
| orexigenic pathway involves ____ which stimulates food ____ and inhibits metabolism --> induces hunger
neuropeptide Y
| intake
175
where is leptin released
from adipocytes
176
how does leptin affect the regulation of food intake?
stimulates the POMC and inhibits the NPY pathway --> induces satiety
177
what hormone inhibits the stimulatory pathway of regulation of food intake
leptin
178
how do gastric stimuli affect the regulation of food intake?
distention of stomach inhibits feeding --> satiety
CCK stimulates insulin release --> satiety
peptide YY released by enteroendocrine cells and inhibit NPY pathway --> satiety
179
how do dopaminergic neurons affect the regulation of food intake?
from the ventral tegmental areas of the midbrain
| stimulates food intake through the reward pathway --> induces hunger
180
where do dopaminergic neurons come from?
from the ventral tegmental areas of the midbrain
181
enzymes and their enzymatic reactions in the digestion of proteins
endopeptidases (serine-protease mechanism):
trypsinogen --> trypsin (by enteropeptidase)
chymotrypsinogen --> chymotrypsin (by trypsin)
proelastase --> elastase (by trypsin)
pepsin - cleaves at N-terminal of hydrophobic AA
carboxypeptidase (metallo protease Zn2+ mechanism):
procarboxypeptidase --> carboxypeptidase (by trypsin)--> 1 of the 2 products below
1. A-C terminus of hydrophobic AAs
2. B-C terminus of basic AAs
182
trypsinogen --> trypsin (by ... )
enteropeptidase
183
chymotrypsinogen --> chymotrypsin (by ... )
trypsin
184
proelastase --> elastase (by ...)
trypsin
185
carboxypeptidase (metallo protease Zn2+ mechanism):
| procarboxypeptidase --> carboxypeptidase (by ...)
trypsin
186
products of breakdown of carboxypeptidase
1. A-C terminus of hydrophobic AAs
| 2. B-C terminus of basic AAs
187
products of protein digestion
tri and tetra peptides which are later cleaved by peptidases
amino acids
188
where does carbohydrate digestion occur and what is the major enzyme involved
mouth and intestine by salivary amylase and pancreatic amylase
189
enzymes involved in carbohydrate breakdown and their enzymatic reactions where applicable.
brush border enzymes of the intestine then complete digestion of disaccharides and oligosaccharides.
disaccharidases - sucrase (sucrose --> glucose) , lactase (glucose and galactose), trehalase (glucose and glucose)
oligosaccharides - glucoamylase and maltase (glucose and glucose) which digests maltose and maltotriose
190
where are brush border enzymes found
small intestine
191
disaccharidases
sucrase (sucrose --> glucose) , lactase (glucose and galactose), trehalase (glucose and glucose)
192
oligosaccharides
glucoamylase and maltase (glucose and glucose) which digests maltose and maltotriose
193
products of carbohydrate digestion
```
glucose
fructose
galactose
maltose
maltotriose
alpha limit dextrins
```
194
villi of the small intestine are covered with ______ cells
columnar epithelial
195
most chyme is absorbed before getting to what area of the GI tract
jejunum
196
explain the absorption of proteins
absorption of peptides is much faster than amino acids
1) Na/H+ exchanger maintains H+ gradient which allows peptides to enter by cotransport
2) once inside, peptides are metabolised into free AAs. they enter the blood by facilitated diffusion
3) glutamate and aspartate are utilised as energy --> not transported
197
absorption of proteins -
| _____ maintains H+ gradient which allows peptides to enter by ___
Na/H+ exchanger
| cotransport
198
absorption of proteins -
| absorption of ____ is much faster than ____
peptides
| amino acids
199
absorption of proteins - once inside, peptides are metabolised into ____ . they enter the blood by ____
free AAs
| facilitated diffusion
200
absorption of proteins -
| ______ are utilised as energy --> not transported
glutamate and aspartate
201
explain the absorption of monosaccharides
occurs either by passive diffusion (very very slow) or facilitated diffusion
APICAL
1) SGLT1 -
cotransport of glucose along with 2Na+
maintained by na/k ATPase pump (secondary active transport)
2) GLUT5 -
facilitated diffusion of fructose into the enterocyte
BASAL
1) GLUT2 -
facilitated diffusion of fructose, glucose, and galactose across basal membrane into blood (one way transport)
2) GLUT1 -
2-way transport of glucose (facilitated) across basal membrane
202
site of protein digestion
stomach (pH2) and intestines
203
action of SGLT1
cotransport of glucose along with 2Na+
| maintained by na/k ATPase pump (secondary active transport)
204
action of GLUT5
facilitated diffusion of fructose into the enterocyte
205
action of GLUT2
facilitated diffusion of fructose, glucose, and galactose across basal membrane into blood (one way transport)
206
action of GLUT1
2-way transport of glucose (facilitated) across basal membrane
207
mechanism of transport by SGLT1
secondary active transport
208
mechanism of transport by GLUT proteins
facilitated diffusion
209
what transport proteins involved in the absorption of monosaccharides are found on the apical border?
SGLT1
| GLUT5
210
what transport proteins involved in the absorption of monosaccharides are found on the basal membrane?
GLUT2
| GLUT1
211
what is the site of lipid digestion and what enzymes are involved
starts in the mouth with lingual lipase and continues into the stomach (gastric lipase) and the small intestine (bile emulsification and pancreatic enzymes)
212
action of lingual lipase and gastric lipase
they are both acid-stable and work in the stomach
| they act on triglycerides with short-medium fatty acid chains (<12)
213
how do bile salts affect lipid digestion
emulsification of lipids by bile salts increases SA for enzymes to work effectively
214
what substance emulsifies lipids
bile salts
215
explain the breakdown of lipids by pancreatic enzymes
pancreatic enzymes are hormonally controlled
1) pancreatic lipase - binds to lipid droplets only in the presence of pancreatic colipase
2) cholesterol esterase - hydrolyses cholesterol esters into cholesterol FAs
3) phospholipase A2 -
activated by trypsin; digests phospholipids --> lysophospholipids by removing 1 FA
4) lysophospholipase - removes the remaining FA at C1, leaving glyceryl phosphoryl
216
action of pancreatic lipase
binds to lipid droplets only in the presence of pancreatic colipase
217
action of cholesterol esterase
hydrolyses cholesterol esters into cholesterol FAs
218
action of phospholipase A2
activated by trypsin; digests phospholipids --> lysophospholipids by removing 1 FA
219
action of lysophospholipase
removes the remaining FA at C1, leaving glyceryl phosphoryl
220
what enzyme binds to lipid droplets only in the presence of pancreatic colipase
pancreatic lipase
221
what enzyme hydrolyses cholesterol esters into cholesterol FAs
cholesterol esterase
222
what enzyme is activated by trypsin; digests phospholipids --> lysophospholipids by removing 1 FA
phospholipase A2
223
what enzyme removes the remaining FA at C1, leaving glyceryl phosphoryl
lysophospholipase
224
what are the primary products of lipid digestion
fatty acids
cholesterol
2-monoacylglycerol
225
explain the process of lipid absorption
1) the products of lipid digestion (fatty acids, cholesterol, 2-monoacylglycerol) are combined with bile salts and phospholipids to form mixed micelles which have a hydrophobic surface
2) the brush border of enterocytes have a water layer through which the micelle cells can pass and are then absorbed into the enterocyte
* short and medium chain FA do not require micelles for absorption)
3) FAs and monoglycerides are transported into the ER to re-synthesize TGs
4) TGs are then grouped with cholesterol, phospholipids, vitamins and apolipoprotein B48 to form chylomicrons and are then excreted into the lymph.
226
formation of a mixed micelle
the products of lipid digestion (fatty acids, cholesterol, 2-monoacylglycerol) are combined with bile salts and phospholipids to form mixed micelles which have a hydrophobic surface
227
formation of a chylomicron
TGs are then grouped with cholesterol, phospholipids, vitamins and apolipoprotein B48 to form chylomicrons and are then excreted into the lymph.
228
digestion of iron
iron can be divided into heme and non-heme (food) iron.
| both are digested by proteases in the stomach and intestine aided by HCl and vitamin C in order to release the iron.
229
in the stomach most non-heme iron is ____.
Fe3+
230
site of digestion of iron
stomach and small intestine
231
enzyme involved in digestion of iron
proteases (aided by HCl and vitamin C for iron release)
232
Explain the absorption of iren
1) HEME IRON
heme is absorbed entirely by the HCP1 (heme carrier protein) and Fe2+ is released from heme by heme-oxidase
2) NON-HEME IRON
Fe3+ (from stomach) is reduced by reductase D cyt B (duodenal cytochrome B) into Fe2+ and is then transported into the enterocyte via the DMT1 (divalent metal transporter)
3) Fe2+ from both the heme and non-heme iron in the enterocyte, are either stored as ferritin (protein) or converted back into Fe3+ by Hephestin where it binds to transferrin for transport around the body. it leave the basolateral membrane via FPN (ferroportin)
4) transferrin-bound iron (Fe3+) is carried to stores and bone marrow where it is absorbed via receptor-mediated endocytosis
5) A CURL (compartment of uncoupling of receptor and ligand) is then formed which releases Fe3+ from transferrin where it is stored as ferritin. Apotransferrin (transferrin without Fe3+) is recycled at the cell surface)
233
describe the breakdown of heme iron
heme absorbed by HCP1
| Fe2+ is released from heme by heme-oxidase
234
what enzyme releases Fe2+ from heme iron
heme-oxidase
235
what protein absorbs heme iron
HCP1
236
describe the breakdown of non-heme iron
Fe3+ is broken down by reductaseD cytB --> Fe2+
| transported into the enterocyte via DMT1
237
what transporter allows for the entry of Fe2+ from the stomach into the enterocyte
DMT1
238
what enzyme is responsible for the breakdown of Fe3+ in the stomach
reductase D cyt B
239
discuss the what happens to Fe2+ as it moves into the enterocyte
either stored as ferritin
| converted back to fe3+ by hephestin which then binds to transferrin and leaves the basolateral membrane via ferroportin
240
what enzyme converts Fe2+ into Fe3+ in the enterocyte
Hephestin
241
what can Fe2+ be stored as
ferritin
242
to leave the enterocyte, Fe3+ must bind to what transport protein?
transferrin
243
what receptor does Fe3+ use to exit the basolateral membrane?
ferroportin
244
transferrin-bound iron (Fe3+) is carried to stores and bone marrow where it is absorbed via _____
receptor-mediated endocytosis
245
what is the function of the formation of a CURL
releases Fe3+ from transferrin where it is stored as ferritin
246
what is ferritin
protein containing ferric oxide hydroxide crystals (FcOOH)
247
what hinders the absorption of iron
```
tanins
oxalate
phytate
inorganic phosphates
antacids
```
248
deficiency of iron
anemia
249
hepcidin
peptide hormone secreted by liver to regulate the entry of iron into circulation
it regulates iron absorption, plasma iron concentration and iron distribution.
250
peptide hormone secreted by liver to regulate the entry of iron into circulation
it regulates iron absorption, plasma iron concentration and iron distribution.
hepcidin
251
what receptor does hepcidin act on?
ferroportin
252
significance of increased hepcidin levels
during infection and inflammation to restrict iron access to pathogens
253
when iron levels drop, storage iron is mobilized first and then haemoglobin synthesis is impaired which leads to ...
microcytic hypochromic anemia
254
microcytic hypochromic anemia
when iron levels drop, storage iron is mobilized first and then haemoglobin synthesis is impaired
255
hemosiderosis
accumulation of ferritin and hemosiderin which leads to free radical generation
256
progression of hemosiderosis
organ damage - hemochromatosis
257
accumulation of ferritin and hemosiderin which leads to free radical generation
hemosiderosis
258
hemochromatosis
organ damage by progression of hemosiderosis
259
precursors of heme
glycine and succinyl coA
260
what determines the half life of a protein
N terminus residues
261
degradation of a protein is done by...
ubiquitination (proteasomal system) or the lysosomal system
262
n terminus of rapidly degraded proteins
```
PEST
proline
glutamine
serine
threonine
```
263
what happens to amino acids in the body - protein turnover
Not stored. reused or broken down by the removal of NH3 group
NH3 goes to the urea cycle and the carbon skeleton is broken down to water and CO2
264
main organs involved in amino acid level regulation and what processes occur in the organs
muscles (aa generation)
| liver (gluconeogenesis, utilization and excretion)
265
function of Glucose - Alanine Cycle
regulates the aa level
266
Glucose - Alanine Cycle
```
(in liver)
Alanine-->pyruvate + NH2
NH2--> urea
Pyruvate --> glucose (transported to muscles)
glucose --> pyruvate
pyruvate lactate
pyruvate alanine (aaalpha keto acid)
(transported to liver)
```
267
how is alanine synthesized
from glucose by the transamination from an amino acid into and alpha keto acid in the muscle.
268
what does the liver convert alanine to
glucose via pyruvate through gluconeogenesis
269
what reaction occurs with the following:
| pyruvate alanine
aaalpha keto acid
270
what class of aa yield TCA intermediates
glucogenic
271
the breakdown of what class of aa yields acetoacetate or acetyl coA. give an example
ketogenic
| leucine and lysine (all essential)
272
examples of aa which are both ketogenic and glucogenic
isoleucine
phenylalanine
tryptophan
(essential)
tyrosine (nonessential)
273
what aa can be made from phenylalanine
tyrosine
274
what aa can be made from
| glycine
serine
275
what aa can be made from
| serine
glycine
276
serine can be further broken to what intermediate in the glycolysis pathway
pyruvate
277
what reaction occurs with the following:
alaninepyruvate
what enzyme is used?
alpha ketoglutarate glutamate
| alanine aminotransferase
278
describe transamination and oxidative deamination
transamination is the transfer of the amino group from an amino acid to an alpha ketoglutarate to form glutamate and an alpha keto acid. vitamin B is used as a coenzyme. the enzyme involved is known as a transaminase.
oxidative deamination is the conversion of glutamate to alpha ketoglutarate by the removal of the NH4+ group .
279
how is glutamine made from glutamate
by the addition of a NH3 group
glutamate --> glutamine
NH3 +ATP --> ADP + Pi
280
how is glutamate made from glutamine
removal of a NH3 group
glutamine --> glutamate
H2O --> NH3
281
transamination of alanine
alanine pyruvate
Alpha ketoglutarate glutamate
enzyme - alanine aminotransferase
282
transamination of aspartate
aspartate oxaloacetate
Alpha ketoglutarate glutamate
enzyme - aspartate aminotransferase
283
what reaction is catalysed by glutamate dehydrogenase
Glutamate --> Alpha ketoglutarate
NAD+ --> NADH
NH3 removed
Alpha ketoglutarate --> glutamate
NADPH --> NAD+
NH3 added
284
describe oxidative and reductive amination
reductive - amino group added to the Alpha ketoglutarate and NADPH oxidized to NAD+ to form glutamate
oxidative - amino group is removed from glutamate and NAD+ is reduced to NADH to form Alpha ketoglutarate
285
significance of the pathway catalysed by glutamate dehydrogenase
synthesis of amino acids§
286
how are amino acids synthesized?
reductive amination followed by transamination
287
how are amino acids disposed
transamination followed by oxidative deamination
288
when the amino group is removed from an aa, they can be degraded into ...
1) intermediate of TCA (glucogenic)
| 2) acetoacetate/ acetyl CoA (ketogenic)
289
Urea Cycle
1) transamination (goes to liver) - amino group removed from aa and added to the alpha ketoglutarate to form glutamate
2) transamination 2 (goes to liver) - aspartate aminotransferase transfers an amino group from glutamate
3) oxidative deamination (in liver) - glutamate is oxidised by glutamate dehydrogenase into Alpha ketoglutarate, releasing NH3
4) NH3 combines with CO2 to form Carbamoyl phosphate using 2ATP
5) carbamoyl phosphate combines with ornithine to form citrulline
6) citrulline combines with aspartate to form argininosuccinate using 1ATP
7) argininosuccinate is then broken down into fumarate and arginine where fumarate can join the TCA cycle to form oxaloacetate with malate.
8) arginine is then hydrated (+ H2O) releasing urea with 2NH4 molecules and hence leaving with ornithine
290
total energy used in urea cycle
3
2 for NH3 to combine with CO2
1 for citrulline to combine with aspartate to form argininosuccinate
291
how many NH4 molecules are formed from 1 urea cycle and what molecules do they arise from
2
1st - glutamate
2nd - aspartate
292
end product of the urea cycle
2 NH4 molecules
293
aspartate is added to what step in the urea cycle and what molecule does it leave as
citrulline --> argininosuccinate
| fumarate
294
what enzyme catalyses the following reaction:
| NH3 combines with CO2 to form Carbamoyl phosphate using 2ATP
carbamoyl phosphate synthetase 1
295
what enzyme catalyses the following reaction:
| carbamoyl phosphate combines with ornithine to form citrulline
ornithine transcarbamylase (OTC)
296
what enzyme catalyses the following reaction:
| citrulline combines with aspartate to form argininosuccinate using 1ATP
argininosuccinate synthase
297
what enzyme catalyses the following reaction:
| argininosuccinate is then broken down into fumarate and arginine
argininosuccinate lyase
298
what enzyme catalyses the following reaction:
| arginine is then hydrated (+ H2O) releasing urea with 2NH4 molecules and hence leaving with ornithine
arginase
299
which molecules involved in the urea cycle are found in the mitochondrial matrix
ornithine
| citrulline
300
what is the significance of the formation of glutamate and aspartate
safely transport NH3 into the liver
301
what occurs if free ammonia levels exceed the capacity of the urea cycle
plasma levels begin to rise causing toxicity to the CNS.
302
cause of hyperammonemia
acquired - liver disease such as OTC deficiency
| inherited - x linked
303
liver disease such as OTC deficiency is a cause of
acquired hyperammonemia
304
explain the body's response to being in the fed state
```
inc insulin
anabolism
liver increases the production of glycogen, proteins, VLDL
adipose cells make triglycerides
muscle - makes protein
```
305
explain the body's response to being in the fasting state
increased glucagon
catabolism
liver - gluconeogenesis, glycogenolysis, Beta oxidation of fatty acids
adipose - lipolysis
muscle - uses FAs and ketone bodies as fuel
brain - uses glucose and ketone bodies
306
ketone bodies are a product of _____
| they are transported to tissues to be converted to ______.
Beta oxidation of fatty acids
| acetyl coA
307
where does gluconeogenesis occur
90% liver
| 10% kidney
308
liver can support blood glucose levels for how long?
10-18 hours
309
substrates for gluconeogenesis
lactate
glycerol
amino acids
310
gluconeogenesis reaction
1) pyruvate carboxylase: pyruvate --> oxaloacetate (cofactor - biotin)
2) PEP carboxykinase: oxaloacetate --> PEP
3) Fructose-1,6-bisphosphatase: fructose-1,6-bisphosphate --> glucose-6-phosphate
4) glucose-6-phosphatase: glucose-6-phosphate --> glucose (glucose-6-phosphate translocase)
311
what enzyme catalyses the following reaction:
| pyruvate --> oxaloacetate
pyruvate carboxylase
| cofactor - biotin
312
what enzyme catalyses the following reaction:
| oxaloacetate --> PEP
PEP carboxykinase
313
what enzyme catalyses the following reaction:
| fructose-1,6-bisphosphate --> glucose-6-phosphate
Fructose-1,6-bisphosphatase
314
what enzyme catalyses the following reaction:
| glucose-6-phosphate --> glucose
glucose-6-phosphatase
| glucose-6-phosphate translocase
315
bonds in glycogen
alpha 1,4 and alpha 1,6 glycosidic bonds
316
where is glycogen stored? function?
liver to maintain blood glucose and muscle as fuel release
317
explain glycogen synthesis
Glycogen synthase adds glucose units to non-reducing ends of an existing glycogen molecule. If there is not glycogen present, glycogenin acts as in new primer to accept glucose units to form in new chain.
318
Building block of glycogen
UDP glucose
319
Describe the structure of glycogenin and its importance in binding with glucose.
Glycogenin has a last residue of tyrosine which joins OH for binding
320
Function of glycogenin
Remains attached to the growing chain and serves as a primer
321
What are the branches of glycogen from by
Branching enzyme - amylo alpha(1,4)-->alpha(1,6) transglucosidase
322
Glycogen synthesis
G-6-P UTP + G-1-P (phosphoglucomutase) [isomerisation]
UTP + G-1-P --> UDP glucose + PPi
(UDP glucose pyrophosphorylase)
[dephosphorylation]
UDP glucose --> glycogenin-G-G-G
(glycogen synthase) glycogenin is incorporated at this step and UDP is removed
323
What are the branches of glycogen removed by
debranching enzyme
324
TGs are resynthesized by what enzyme and from what
acyl coA and 2-monoacylglycerol
| enzyme - acyl coA synthase
325
acyl coA is made up of
FA + coA
326
when fat is in the lymph, where does it enter the blood stream
thoracic duct
327
glycogen phosphorylase
cleaves alpha 1-4 glycosidic bonds succeeding at the non-reducing ends, releasing them as glucose-1-phosphate
this enzyme stops at 4 residues before each branch, leaving a structure called limit dextrin which is removed by a debranching enzyme
328
glycogen break down
1) glycogen phosphorylase: cleaves alpha 1-4 glycosidic bonds succeeding at the non-reducing ends, releasing them as glucose-1-phosphate
2) this enzyme stops at 4 residues before each branch, leaving a structure called limit dextrin which is removed by a debranching enzyme
3) G-1-P is then converted to G-6-P by phosphoglucomutase (same enzyme used in glycogen synthesis)
4) in the liver, G-6-P is changed into glucose by glucose-6-phosphorylase as it enters the blood
329
glycogen breakdown - glycogen phosphorylase stops at 4 residues before each branch, leaving a structure called _____ which is removed by a _____
limit dextrin
| debranching enzyme
330
phosphoglucomutase
G-1-P is then converted to G-6-P
331
G-6-P is changed into glucose by
glucose-6-phosphorylase
332
G-1-P is then converted to G-6-P by
phosphoglucomutase
333
glycogen phosphorylase cleaves ____ and releases them as _____
alpha 1-4 glycosidic bonds
| glucose-1-phosphate
334
regulation of glycogen
glycogen synthase and glycogen phosphorylase respond to:
1. allosteric regulation -
G-6-P allosterically activates glycogen synthase and inhibits glycogen phosphorylase
in the muscle, Ca2+ and AMP activate glycogen phosphorylase as they indicate the need for energy
2. hormonal regulation -
glucose synthase is activated when it is unphosphorylated
glucose phosphorylase is active when it is phosphorylated
glycogen (non - fed) and adrenaline (need for energy) activate cAMP dependant PKA which promotes phosphorylation
--> promotes glycogen phosphorylase --> increases glycogen breakdown --> increases glucose
--> inhibits glycogen synthase
335
adipose tissue lipase
hormone sensitive enzyme that is responsible for breakdown of fat --> active when phosphorylated (activated by glucagon and adrenaline)
336
hormone sensitive enzyme that is responsible for breakdown of fat
adipose tissue lipase
337
activation of adipose tissue lipase
active when phosphorylated (activated by glucagon and adrenaline)
338
allosteric regulation of glycogen
G-6-P allosterically activates glycogen synthase and inhibits glycogen phosphorylase
in the muscle, Ca2+ and AMP activate glycogen phosphorylase as they indicate the need for energy
339
G-6-P allosterically activates ____ and inhibits _____
glycogen synthase
| glycogen phosphorylase
340
in the muscle, ____ activate glycogen phosphorylase
Ca2+ and AMP
341
hormonal regulation of glycogen
glucose synthase is activated when it is unphosphorylated
glucose phosphorylase is active when it is phosphorylated
glycogen (non - fed) and adrenaline (need for energy) activate cAMP dependant PKA which promotes phosphorylation
--> promotes glycogen phosphorylase --> increases glycogen breakdown --> increases glucose
--> inhibits glycogen synthase
342
hormonal regulation of glycogen - _____ is activated when it is unphosphorylated
glucose synthase
343
hormonal regulation of glycogen - _____ is active when it is phosphorylated
glucose phosphorylase
344
hormonal regulation of glycogen. - glucose synthase is activated when it is ______
unphosphorylated
345
hormonal regulation of glycogen - glucose phosphorylase is active when it is _____
phosphorylated
346
hormonal regulation of glycogen - ______ activate cAMP dependant PKA which promotes phosphorylation
glycogen (non - fed) and adrenaline (need for energy)
347
hormonal regulation of glycogen -
| glycogen (non - fed) and adrenaline (need for energy) activate _____ which promotes ______
cAMP dependant PKA
| phosphorylation
348
comment on the promotion and inhibition of hormones in the hormonal regulation of glycogen
- -> promotes glycogen phosphorylase --> increases glycogen breakdown --> increases glucose
- -> inhibits glycogen synthase
349
GSDs
glycogen storage disorders
| abnormal synthesis or breakdown of glycogen
350
GSD1
von gierke's disease - G-6- phosphatase deficiency
inability to produce glucose by gluconeogenesis
inability to maintain glucose levels (hypoglycemia)
351
inability to produce glucose by gluconeogenesis
| inability to maintain glucose levels (hypoglycemia)
von gierke's disease - G-6- phosphatase deficiency
| GSD1
352
von gierke's disease
G-6- phosphatase deficiency
GSD1
inability to produce glucose by gluconeogenesis
inability to maintain glucose levels (hypoglycemia)
353
GSD V
McArdle Disease
muscle glycogen phosphorylase deficiency
muscle cannot breakdown glycogen
muscle fatigue
354
McArdle Disease
GSD V
muscle glycogen phosphorylase deficiency
muscle cannot breakdown glycogen
muscle fatigue
355
muscle glycogen phosphorylase deficiency
muscle cannot breakdown glycogen
muscle fatigue
McArdle Disease
| GSD V
356
G-6- phosphatase deficiency
von gierke's disease
| GSD1
357
muscle glycogen phosphorylase deficiency
McArdle Disease
| GSD V
358
conversion of aa in lipid absorption
apolipoprotein b48
359
conversion of monoacylglycerol in lipid absorption
TG by acyl coA synthase
360
conversion of cholesterol in lipid absorption
cholesterol ester
361
path of components in lipid absorption
apolipoprotein b48, TG, cholesterol ester, fat soluble vitamins, phospholipids ---> chylomicron ---> lymphatics ---> thoracic duct
362
where are Lipoprotein lipases found
most tissue except for brain and liver
363
the adipose LPL os attached to _________ on the surface of the capillary epithelium
heparan sulphate glycoproteins
364
what occurs when chylomicrons bind to LPL
hydrolyse TGs directly
365
the binding of ___ and ____ hydrolyse TGs directly
chylomicrons and LPL
366
after a meal, where do the fatty acids involved in TG synthesis come from
chylomicrons
367
what does adipose tissue release
unesterified FA
| free FA
368
where does TG synthesis occur
adipose but also in liver and ammary glands
369
FAs participate in TG synthesis in the form of ____ and ___ as G-3-P (biproduct of glycolysis)
what enzyme is uses?
** this is the rate limiting step
thioesters
glycerol
enzyme - glycerol phosphate-acyltransferase
370
glycerol phosphate-acyltransferase
used in the synthesis of TG
371
what stimulates TG synthesis
insulin which:
increase glycolysis --> increase G-3-P
increased LPL activity
induces glycerol phosphate-acyltransferase
372
TG breakdown is catalysed by ____ and occurs by the stepwise removal of _____
lipase
| each of the 3FA
373
rate limiting step of TG breakdown
first cleavage
374
how is lipase activated in TG breakdown
similar to glycogen breakdown, lipase is activated through phosphorylation by PKA as well as SNS innervation
adrenaline and glucagon also stimulates it
375
what induces lipid breakdown
glucocorticoids, GH, TH
376
Beta oxidation
this is a 2 step process which occurs in all cell types that have a mitochondria
1. transport - shorter FAs can enter the mitochondrial membrane by passive diffusion whilst long chain FA require carriers eg. carnitine shuttle (CPT1 and CPT2)
a. FAs are converted into their coA thioesters --> FA coA which then crosses the outer membrane
b. CPT1 on the outer membrane replace the coA with carnitine --> FA carnitine goes through the inner membrane with translocase
c. CPT2 on the inner membrane removes carnitive and adds back acetyl coA --> FAcoA. carnitine is then sent back into the intermembrane space through a translocase again
2. beta oxidation
cyclic reaction where 2Cs --> 1 NADH and 1 FADH2 --> 5ATP
acetyl coA is not a substance for gluconeogenesis but stimulates pyruvate carboxylase ( pyruvate --> oxaloacetate)
goal - generate ATP/energy from FA oxidation
377
what cell type can beta oxidation not occur
RBC (not with mitochondria)
378
transport of long chain FA
a. FAs are converted into their coA thioesters --> FA coA which then crosses the outer membrane
b. CPT1 on the outer membrane replace the coA with carnitine --> FA carnitine goes through the inner membrane with translocase
c. CPT2 on the inner membrane removes carnitive and adds back acetyl coA --> FAcoA. carnitine is then sent back into the intermembrane space through a translocase again
379
what provides FAs for ketone production and in what form are they released?
adipose tissue
| released as thioesters
380
what transporters are found on the outer membrane of the mitochondria?
CPT1
381
what transporters are found on the inner membrane of the mitochondria?
CPT2
| translocase
382
beta oxidation
| cyclic reaction
removal of 2Cs (from FA coA) --> 1 NADH and 1 FADH2 --> 5ATP
acetyl coA is not a substance for gluconeogenesis but stimulates pyruvate carboxylase ( pyruvate --> oxaloacetate)
goal - generate ATP/energy from FA oxidation
383
what enzyme involved in gluconeogenesis is stimulated by acetyl coA. what does it do?
pyruvate carboxylase ( pyruvate --> oxaloacetate)
384
regulation of beta oxidation
malonyl coA is the first intermediate in FA synthesis and inhibits CPT1 --> FA synthesis and beta oxidation cannot occur at the same time
beta oxidation is dependant on the supply of free FA --> proportional to activity of adipose tissue
385
what does CPT1 do
replace the coA with carnitine --> FA carnitine
386
what does CPT2 do
removes carnitive and adds back acetyl coA --> FAcoA.
387
FA synthesis and beta oxidation cannot occur at the same time. why?
malonyl coA is the first intermediate in FA synthesis and inhibits CPT1
388
malonyl coA
first intermediate in FA synthesis and inhibits CPT1
| FA synthesis and beta oxidation cannot occur at the same time.
389
what enzyme inhibits CPT1?
malonyl coA
390
beta oxidation is dependant on the _______ which is proportional to ______
supply of free FA
| activity of adipose tissue
391
ketogenesis - acetoacetate and beta hydroxybutyrate
ketone bodies, namely acetoacetate and beta hydroxybutyrate, are formed from acetyl coA in the liver mitochondrial cells ONLY.
They can also join the TCA cycle via acetyl coA
392
ketone bodies
acetoacetate
beta hydroxybutyrate
acetone
393
ketogenesis - acetone
formed by spontaneous decarboxylation of acetoacetate
394
acetone is formed from the decarboxylation of
acetoacetate
395
decarboxylation of acetoacetate forms
acetone
396
the ketogenesis of acetone is a what type of rxn
decarboxylation
397
acetyl coA can contribute to
TCA cycle
ketone bodies
oxaloacetate
398
importance of ketone bodies
ketone bodies are important as they are transported to the heart, adrenal glands and renal cortex to be reconverted back to acetyl coA to be used in the TCA cycle. this represents the main energy source for these organs
399
use of brown adipose
| characterised by
```
heat metabolism (instead of ATP)
it is characterised by good blood supply, mitochondria and cytochromes but low ATP synthase
```
400
MCADD
deficiency of medium chain acyl coA dehydrogenase which represents the first rate limiting step of beta oxidation.
it leads to the intolerance to fasting, impaired ketogenesis and hypoglycemia.
401
deficiency of medium chain acyl coA dehydrogenase
MCADD
| leads to the intolerance to fasting, impaired ketogenesis and hypoglycemia.
402
circulating levels of ketone bodies are normally very low but increases during
fasting, diabetes, when fat breakdown is more than carb breakdown
403
electrical impedance uses
higher resistance of fat that water to take measurements
404
most accurate way to measure body fat
dual z-ray absorption
405
relationship of BMI and mortality
v or J shaped relationship curve but waist circumference is a better tool
406
metabolically healthy obese individuals have
normotension
normal lipid profile
normal liver function
low visceral/ ectopic fat
407
what is visceral/ectopic fat
dangerous kind of fat since it is hormonally active
408
obesity paradox
obese patients are more likely to suffer a heart attack but less likely to die from it
409
____ is a better indication to mortality than ____
fitness
| weight
410
when fitness is involved, ___________ has no effect on mortality
BMI
| pattern of exercise
411
for people with high muscle mass or for adolescents, BMI should be measured by
kg/m^3 instead of kg/m^2
412
eating hormones
1. ghrelin - produced in the stomach - triggers desire to eat by binding to the secretagogue
receptor in the arcuate nucleus in the brain, associated with dopamine response pathway
2. leptin - produced by adipose tissue - triggers satiety. increases POMC secretion
receptor also in arcuate nucleus in the brain
413
ghrelin produced by
stomach
414
ghrelin
triggers desire to eat by binding to the secretagogue
| receptor in the arcuate nucleus in the brain, associated with dopamine response pathway
415
ghrelin bind to
secretagogue
| receptor in the arcuate nucleus in the brain
416
leptin produced by
adipose tissue
417
leptin
triggers satiety. increases POMC secretion
| receptor also in arcuate nucleus in the brain
418
leptin receptor
receptor also in arcuate nucleus in the brain
419
POMC secretion is increased by
leptin
420
enzyme that triggers desire to eat
ghrelin
421
enzyme that triggers satiety
leptin
422
weight loss in people with obesity causes changes in
appetite hormones (leptin and ghrelin) that can increase hunger for up to 1 year
423
_____ is used in patients who failed to lose weight through dietary eg. ____
pharmacotherapy
| orlistat
424
liposuction reduces ______ not _____. comment on its efficiency.
subcutaneous fat
visceral fat
therefore has no benefit
425
Bariatric surgery
reduces the consumption and absorption of food
426
reduces the consumption and absorption of food
Bariatric surgery
427
Bariatric surgery is recommended for
people with a BMI above 40
hyperlipidemia
hypertension
diabetes
428
stages of weight complications
0 - no complications - if overweight - lifestyle therapy, if obese - pharmacotherapy and weight loss medication
1 - mild/ moderate complications - weight loss medication
2 - severe complications - bariatric surgery
429
kwashiorkor
inadequate protein intake - edema, peeling skin, pigmented hair
430
malnutrition is graded on a
graded on a z-scale
wasting is -2 to -3 based on weight/height
stunting is -2 to -3 based on height
431
treating malnutrtion
phase 1 -
rehydration - resomal (reduced Na and increased K)
feeding - RTUF (ready to use therapeutic food) with high energy or
F-75 = 75 kcal/day if the child cannot tolerate RUTF
phase 2 -
rehabilitation - switched to F-100 - slowly increase to 150-220 kcal/day until wt/ht z scale is greater than -1
also include vitamin supplements
switch to RUTF asap
432
cachexia
loss of muscle with/ without loss of fat
433
loss of muscle with/ without loss of fat
cachexia
434
refeeding syndrome
when someone with severe anorexia suddenly starts eating normally
435
when someone with severe anorexia suddenly starts eating normally
refeeding syndrome
436
fluoxetine
serotonin reuptake inhibitor to reduce binge eating
437
serotonin reuptake inhibitor to reduce binge eating
fluoxetine
438
effect of glucocorticoids and progesterone
stimulate appetite
439
treatment of cancer cachexia
thalidomide
440
thalidomide
treatment of cancer cachexia
441
what stimulates appetite
effect of glucocorticoids and progesterone
| ghrelin
442
structure function of the zones of the liver
perivenous -
O2 poor region around the central hepatic vein
glutamine synthase
periportal -
O2 rich region around the portal vein
urea cycle takes place here.
443
perivenous zone
O2 poor region around the central hepatic vein
| glutamine synthase
444
in what zone is glutamine synthase found
perivenous zone
445
what is the O2 poor region of the liver
perivenous zone
446
periportal zone
O2 rich region around the portal vein
| urea cycle takes place here.
447
in what zone does the urea cycle take place
periportal zone
448
what is the O2 rich region of the liver
periportal zone
449
main vessel in the periportal zone
portal vein
450
main vessel in the perivenous zone
central hepatic vein
451
explain blood flow in the zones of the liver
periportal zone --> midzone --> perivenous zone
452
biosynthetic function of the liver
FATS
1. TG - converts excess carbs and proteins into FA and TGs for adipose tissue
2. cholesterol and phospholipids - some packaged into lipoproteins and exported to the rest of the body. others are secreted in bile
3. lipoproteins - most synthesised in the liver
CARBOHYDRATES
Glucose from gluconeogenesis
PROTEINS made by the liver
1. non-essential aas
2. plasma proteins (albumin)
3. clotting factors (fibrinogen)
4. acute phase proteins (alpha and beta globulins)
* * structural proteins and enzymes are exported proteins
```
OTHERS
ketone bodies
bile acids
urea
nucleotide precursors (purine and pyrimidine)
```
453
biosynthetic function of the liver - FATS
1. TG - converts excess carbs and proteins into FA and TGs for adipose tissue
2. cholesterol and phospholipids - some packaged into lipoproteins and exported to the rest of the body. others are secreted in bile
3. lipoproteins - most synthesised in the liver
454
cholesterol and phospholipids are packed into
lipoproteins
455
what fat is most synthesised in the liver
lipoproteins
456
biosynthetic function of the liver - CARBOHYDRATES
Glucose from gluconeogenesis
457
biosynthetic function of the liver - proteins
1. non-essential aas
2. plasma proteins (albumin)
3. clotting factors (fibrinogen)
4. acute phase proteins (alpha and beta globulins)
* * structural proteins and enzymes are exported proteins
458
biosynthetic function of the liver - OTHERS
ketone bodies
bile acids
urea
nucleotide precursors (purine and pyrimidine)
459
where is albumin synthesised
albumin is only synthesised in the liver by hepatic cells
| it is regulated by stress
460
what regulates albumin synthesis
stress
461
albumin synthesis
1. synthesised as pre proalbumin with aa extension at the N- terminal
2. aa extension inserted into the ER membrane
3. majority of extension cleaves in lumen leaving proalbumin
4. proalbumin exported to golgi where extension is removed --> albumin
5. albumin excreted directly --> not stored
462
comment of the production and storage of albumin
only produced when needed
not stored (based on plasma concentration of colloid in hepatic interstitium)
**applies to periods without stress
463
trace the path of albumin when it leaves
passes directly into the hepatic sinusoids until reaching the space of disse (parasinusoidal space) and enters the lymphatic system where it finally ends back into circulation at the thoracic duct
464
albumin synthesis - synthesised as ___ with aa extension at the ____
pre proalbumin
| N- terminal
465
albumin synthesis -
| aa extension inserted into the _____
ER membrane
466
albumin synthesis -
| majority of extension cleaves in lumen leaving _____
proalbumin
467
albumin synthesis -
| proalbumin exported to ____ where extension is removed and ____ is produced
golgi
| albumin
468
path of albumin when it leaves-
passes directly into the _______ until reaching the ______ and enters the _______ where it finally ends back into circulation at the _____
hepatic sinusoids
space of disse (parasinusoidal space)
lymphatic system
thoracic duct
469
what do alpha and beta globulins indicate
they are acute phase proteins that indicate disease or malnutrition of the acute phase response
470
what are alpha and beta globulins cleared by
asia glycoproteins on the surface of the hepatocyte
471
asia glycoproteins
clears alpha and beta globulins
472
where are asia glycoproteins found
surface of the hepatocyte
473
describe the structure of haem
ferrous iron surrounded by a porphyrin ring
474
where is Hb synthesised?
bone marrow
475
where is heme synthesized?
liver
476
myoglobin is synthesised by
muscle
477
cytochrome p450 and catalase are synthesised by the
liver
478
how many enzymes are involved in heme synthesis and where are they found
8
4 in mitochondria
4 in cytosol
479
heme synthesis
1. succinyl coA + glycine --> ALA (ALA synthase - mitochondria)
**RLS
inhibited by non-protein bound heme (free heme) by negative feedback. heme also stimulates globin synthesis to ensure low levels of free heme. (protein-bound heme does not inhibit ALA synthase)
2. 2ALA --> PBG (ALA dehydrogenase - cytoplasm)
*this enzyme has sulphurdural group which is inhibited by heavy metal (Pb2+)
ALA is transported into the cytoplasm
3. 4PBG --> hydroxymethylbilane (PBG deaminase and UP-cosynthase)
hydroxymethylbilane --> UP1 (UP synthase 1)
UP1 --> UP3
* enzymes in cytoplasm
4. decarboxylation of UP3 --> 5CO2H (UP decarboxylase)
this allows for the transfer back into the mitochondria.
5. decarboxylation into the mitochondria involves changing the side groups
acetate --> methyl
propionate --> vinyl
6. chelation (insertion) of iron forms the free heme which inhibits ALA synthase
480
production of ALA
succinyl coA + glycine --> ALA (ALA synthase - mitochondria)
**RLS
inhibited by non-protein bound heme (free heme) by negative feedback. heme also stimulates globin synthesis to ensure low levels of free heme. (protein-bound heme does not inhibit ALA synthase)
481
what enzyme produces ALA
ALA synthase
482
where is ALA synthase found
mitochondria
483
inhibitors of ALA production
inhibited by non-protein bound heme (free heme) by negative feedback
484
what does heme stimulate to ensure low levels of free heme
globin synthesis
485
what is the importance of gloin synthesis by heme
to ensure low levels of free heme
486
_____ heme does not inhibit ALA synthase
protein-bound
487
2ALA --> ____
what is the enzyme involved
where does this take place
PBG
ALA dehydrogenase
cytoplasm
488
explain the inhibition of ALA dehydrogenase
*this enzyme has sulphurdural group which is inhibited by heavy metal (Pb2+)
489
in heme synthesis, heavy metals inhibit ...
ALA dehydrogenase
490
in heme synthesis, after the formation of PBG, where is ALA transported
into the cytoplasm
491
4PBG --> ______
what enzyme is involved
where does this take place
hydroxymethylbilane
PBG deaminase and UP-cosynthase
cytoplasm
492
____ --> hydroxymethylbilane
4PBG
493
hydroxymethylbilane --> _____
enzyme involved
location
UP1
UP synthase 1
cytoplasm
494
_____ --> UP1
hydroxymethylbilane
495
UP1 --> ____
UP3
496
____ --> UP3
UP1
497
____ --> PBG
2ALA
498
UP3 --> ____
what type of reaction is this
enzyme involved?
importance of step?
5CO2H
decarboxylation
UP decarboxylase
allows for the transfer back into the mitochondria.
499
heme synthesis - decarboxylation into the mitochondria involves
changing the side groups
acetate --> methyl
propionate --> vinyl
500
decarboxylation into the mitochondria involves changing the side groups
____ --> methyl
acetate
501
decarboxylation into the mitochondria involves changing the side groups
acetate --> ____
methyl
502
decarboxylation into the mitochondria involves changing the side groups
____ --> vinyl
propionate
503
decarboxylation into the mitochondria involves changing the side groups
propionate --> ____
vinyl
504
____ of iron forms the free heme which inhibits _____
chelation (insertion)
| ALA synthase
505
what inhibits ALA synthase
chelation (insertion) of iron forms the free heme which inhibits ALA synthase
506
porphyrias
defects of heme synthesis leading to decreased synthesis (complete loss = death)
this can lead to toxic intermediates
no heme = no feedback = increase in toxic intermediate
507
porphyrias
defects of heme synthesis leading to decreased synthesis (complete loss = death)
this can lead to toxic intermediates
no heme = no feedback = increase in toxic intermediate
508
AIP - acute intermittent porphyrias
acute intermittent porphyrias is a defect in UP synthase 1 and hence there is no conversion of PBG to UP1
509
defects of heme synthesis leading to decreased synthesis
porphyrias
510
defect in UP synthase 1 and hence there is no conversion of PBG to UP1
AIP - acute intermittent porphyrias
511
a defect of what enzyme prevents conversion of PBG to UP1
| name of illness
UP synthase 1
| AIP - acute intermittent porphyrias
512
danger of porphyrias
this can lead to toxic intermediates
| no heme = no feedback = increase in toxic intermediate
513
ALA and PBG accumulation treatment
inhibit ALA synthase to prevent building up of PBG
514
Regulation of heme synthesis
1. negative feedback of free heme on ALA synthase
2. heavy metals inhibit ALA dehydratase and chelation of iron
3. Iron overload affects UP1-->UP3 (flipping of side chains)
515
cutaneous manifestations of porphyrias
deficiency in UP decarboxylase which causes the accumulation of porphyrins and porphyrinogens which are photosensitive --> cause cellular damage when exposed to light
516
deficiency in UP decarboxylase which causes the accumulation of
porphyrins and porphyrinogens which are photosensitive --> cause cellular damage when exposed to light
517
what step of heme synthesis utilizes UP decarboxylase
decarboxylation of UP3 --> 5CO2H (UP decarboxylase)
| this allows for the transfer back into the mitochondria.
518
negative feedback of free heme on _____
ALA synthase
519
heavy metals inhibit
ALA dehydratase and chelation of iron
520
Iron overload affects UP1-->UP3 (flipping of side chains)
UP1-->UP3 (flipping of side chains)
521
metabolism is involved with transforming lipophilic --> ____ for excretion
hydrophilic
522
what are the phases of drug metabolism
phase 1 involves the transformation of a drug into a more polar metabolite in preparation for phase. 2
oxidation (cyt P450), reduction or hydrolysis.
phase 2 involves the combination of glucuronic acid, sulfate, acetic acids or aa with a functional group that may not be from phase 1
523
phase 1 involves the transformation of a drug into a more ______ in preparation for phase. 2
the processes involved are _____________________
polar metabolite
| oxidation (cyt P450), reduction or hydrolysis.
524
phase 2 involves the combination of ________ with a ______ that may not be from phase 1
glucuronic acid, sulfate, acetic acids or aa
| Functional group
525
where is the oxidation of metabolites done
cytoplasm
526
phase 1
1. oxidation hydroxylation - addition of an OH group eg. lidocaine
2. oxidation dehy
527
phase 1
1. oxidation hydroxylation - addition of an OH group eg. lidocaine
2. oxidation dehydrogenation- removal of H eg. metabolism of ethanol
step 1 - oxidation in ER
ethanol --> acetaldehyde [NAD+ --> NADH] (alcohol dehydrogenase)
step 2 - oxidation in the mitochondria
acetaldehyde --> acetate [NAD+ --> NADH] (aldehyde dehydrogenase)
**note the treatment of alcohol abuse
3. oxidation dealkylation - replaces alkyl group with an aldehyde or OH
4. reduction - removal of O or addition of H or e-
eg. R-NO2 --> R-NH2
```
5. hydrolysis - addition of H2O (normally to an ester)
uses esterases
eg. R-O-C - CH3 --> R-OH
II
O
```
528
treatment of alcohol abuse
disulfiram (stored in adipose tissue)
| inhibits oxidation of acetaldehyde into acetate by competing with NAD+ cofactor for binding on ALDH --> hangover
529
oxidation hydroxylation
addition of an OH group eg. lidocaine
530
oxidation dehydrogenation
removal of H eg. metabolism of ethanol
step 1 - oxidation in ER
ethanol --> acetaldehyde [NAD+ --> NADH] (alcohol dehydrogenase)
step 2 - oxidation in the mitochondria
acetaldehyde --> acetate [NAD+ --> NADH] (aldehyde dehydrogenase)
531
oxidation dehydrogenation-
| where does step 1 occur
ER
532
oxidation dehydrogenation-
| where does step 2 occur
mitochondria
533
oxidation dehydrogenation- step 1
ethanol --> acetaldehyde
what is the accompanying equation
what enzyme is used
oxidation in ER
[NAD+ --> NADH]
(alcohol dehydrogenase)
534
oxidation dehydrogenation- step 1
| ethanol --> ____
acetaldehyde
535
oxidation dehydrogenation- step 2
acetaldehyde --> _____
what is the enzyme used
acetate
| aldehyde dehydrogenase
536
where is disulfiram found
(stored in adipose tissue)
537
purpose and action of disulfiram
treatment of alcohol
| inhibits oxidation of acetaldehyde into acetate by competing with NAD+ cofactor for binding on ALDH --> hangover
538
inhibits oxidation of acetaldehyde into acetate by competing with NAD+ cofactor for binding on ALDH
disulfiram
539
phase 1 reactions
| what process replaces alkyl group with an aldehyde or OH
oxidation dealkylation
540
removal of O or addition of H or e-
reduction
541
addition of H2O (normally to an ester)
hydrolysis
542
phase 2
1. glucuronic acid
acts on drugs with OH, COOH and NH3
replaces H with GA by Glucuronyl transferase
R-OH --> R-O-GA [UDP-GA-->UDP]
2. sulphate conjugation
acts on aromatic compounds with OH and NH2
comes between the O and H of OH and replaces the NH2
conjugates with GA conjugation (paracetamol)
R-O-H --> R-OSO3H
(PAPS and sulfurtransferase)
3. glycine conjugation
acts COOH groups, replaces OH with glycine
4. glutathione conjugation
acts on epoxides, halides or electrophilic compounds
replaces H with SG and =O has H added --> =SOH
543
glucuronic acid
| acts on drugs with
OH, COOH and NH3
544
glucuronic acid
acts on drugs with OH, COOH and NH3
replaces __ with __ by _________
H
GA
Glucuronyl transferase
545
sulphate conjugation
| acts on
aromatic compounds with OH and NH2
546
sulphate conjugation
acts on aromatic compounds with OH and NH2
comes between ______ and replaces the ____
conjugates with _______ (paracetamol)
what enzymes are used?
the O and H of OH
NH2
GA conjugation
enzymes - (PAPS and sulfurtransferase)
547
glycine conjugation
acts on ________
replaces ___ with ______
COOH groups
OH
glycine
548
glutathione conjugation
acts on _________
replaces __ with ___ and =O has H added --> =SOH
epoxides, halides or electrophilic compounds
H
SG
549
metabolism of aspirin
phase 1 - esterases --> hydrolysis
phase 2 -
low doses - glycine conjugation (glycine transferase)
high doses - glucuronic conjugation (since first pathway is saturated)
top doses - urinary excretion (since both pathways saturated)
550
what phase 1 reaction uses esterases
hydrolysis
551
conjugation of drug with COOH groups
glucuronic acid
| glycine conjugation
552
conjugation of
| aromatic compounds with OH and NH2
sulphate conjugation
553
conjugation of
| OH, COOH and NH3
glucuronic acid
554
conjugation of
| epoxides, halides or electrophilic compounds
glutathione conjugation
555
metabolism of aspirin
| low doses
glycine conjugation (glycine transferase)
556
metabolism of aspirin
| high doses
glucuronic conjugation (since first pathway is saturated)
557
metabolism of aspirin
| top doses
urinary excretion (since both pathways saturated)
558
metabolism of paracetamol
phase 1 - oxidation dehydrogenase (only for glutamine pathway, making it lipophilic)
phase 2 -
main pathway - glucuronic conjugation (GA transferases)
major pathway - sulfate conjugation (PAPS and Sulfotransferase)
**the 2 above do not need first pass metabolism (skips phase)
minor pathway - glutathione conjugation (glutathione transferases)
559
phase 1 reaction of aspirin
hydrolysis - esterases
560
high doses of paracetamol build up causes
building up of electrophilic intermediate of glutathione pathway called NAPQI which at high concentrations can attack the liver
n - acetyl cysteine relieves this problem by stimulating glutathione production
561
NAPQI
intermediate of glutathione pathway
562
excess NAPQI
at high concentrations can attack the liver
563
relief of high doses of paracetamol build up
n - acetyl cysteine
564
how does n - acetyl cysteine relieve high doses of paracetamol build up
stimulating glutathione production
565
what stimulates glutathione production
n - acetyl cysteine
566
phase 1 of the paracetamol metabolization accompanies which pathway of phase 2
minor pathway - glutathione conjugation (glutathione transferases)
567
metabolism of paracetamol - main pathway
glucuronic conjugation (GA transferases)
568
metabolism of paracetamol
| major pathway
sulfate conjugation (PAPS and Sulfotransferase)
569
metabolism of paracetamol
| minor pathway
glutathione conjugation (glutathione transferases)
570
prodrugs
important since it requires this biotransformation to become active
571
specific drug delivery
| sulfasalazine
sulfasalazine --> 5-ASA for ulcerative colitis. this drug acts on the colon but cannot reach it without being absorbed
sulfasalazine can then reach the colon where azo reductases cleave the N-(triple bond)-N bond, releasing 5-ASA
572
specific drug delivery
| morphine
diamorphine --> morphine
diamorphine has 2 acetylated OH groups compared to morphine, making it hydrophobic --> can cross BBB where esterases can then cleave the acetylation revealing OH groups
573
specific drug delivery
sulfasalazine
sulfasalazine --> _____ for ulcerative colitis. this drug acts on the ____ but cannot reach it without being absorbed
sulfasalazine can then reach the colon where ______ cleave the _____ bond, releasing 5-ASA
5-ASA
colon
azo reductases
N-(triple bond)-N
574
specific drug delivery
diamorphine
diamorphine --> _____
diamorphine has 2 acetylated OH groups compared to morphine, making it hydrophobic --> can cross BBB where _____ can then cleave the acetylation revealing OH groups
morphine
| esterases
575
explain the improved physicochemical properties of
| enalaprilat
enalapril --> enalaprilat (esterases)
enalaprilat is a poorly absorbed ACE inhibitor due to its polarity. The ethalester on enalapril is hydrophobic --> easily absorbed
576
prolonged drug release - haloperidol
haloperidol decanoate --> haloperidol (esterases)
haloperidol is used to treat psychotic disorders (non-compliance).
haloperidol decanoate has a long ester --> when injected, the slow conversion rate allows effects to last 1 month
577
bile stored in the liver is more ___ whereas bile stored in the gallbladder is more ____ and has more solid materials such as ________
diluted
concentrated
cholesterol, phospholipids, mobile salts
578
functions of bile
1. excretory
releases bile pigments, cholesterol, bile acids, salts, drugs and particulate matter removed from blood by kupffer cells in the liver
2. digestive
bile is rich is bicarbonate which neutralises gastric acid.
bile salts emulsify fats into small droplets
579
excretory
releases bile pigments, cholesterol, bile acids, salts, drugs and particulate matter removed from blood by ______ in the liver
kupffer cells
580
formation of bile salts
1. cholesterol breaks down into cholic acid and chemosensory cholic acid
2. acids are conjugated with glycine and taurine
3. conjugated bile acid - na+ or k+ makes it a bile salt
4. in the gut, bacterial alpha dehydroxylase
converts conjugated cholic acid into deoxycholic acid
converts conjugated chenodeoxycholic acid into lithocholic
** these are known as secondary bile salts and can be absorbed back into liver again and process restarts.
581
bile is rich is bicarbonate which
neutralises gastric acid.
582
formation of bile salts -
| cholesterol breaks down into
cholic acid and chemosensory cholic acid
583
formation of bile salts -
| acids are conjugated with
glycine and taurine
584
conjugated bile acid - _____ makes it a bile salt
na+ or k+
585
in the gut, bacterial alpha dehydroxylase :
converts conjugated cholic acid into ____
converts conjugated chenodeoxycholic acid into _____
deoxycholic acid
| lithocholic
586
what is bilirubin
natural degradation of heme of erythrocytes after being phagocytosed in the spleen, liver or bone marrow
587
degradation of RBC and bilirubin
RBC --> Hemoglobin --> globin --> aa
Hb --> heme --> bilirubin --> excreted
heme --> fe2+
588
handling of free Hb
1. scavenge and recycle iron -
haptoglobin is complexed with Hb and metabolized in the liver and spleen forming an iron-globin complex and bilirubin to prevent loss of iron in urine.
2. prevent major iron losses -
hemopexin binds to free forming heme - hemopexin incomplete and taken up by the liver and stored as ferritin
3. methemalbumin - complex of oxidized heme and albumin
589
handling of free Hb
scavenge and recycle iron -
_____ is complexed with Hb and metabolized in the liver and spleen forming an ____________ to prevent loss of iron in urine.
haptoglobin
| iron-globin complex and bilirubin
590
handling of free Hb
prevent major iron losses -
_____ binds to free forming ________ in complex and taken up by the liver and stored as _____
hemopexin
heme - hemopexin
ferritin
591
handling of free Hb
| methemalbumin - complex of
oxidized heme and albumin
592
bruises
RED --> purple = hemoglobin
yellow --> GREEN = biliverdin
YELLOW --> purple = bilirubin
593
metabolism of bilirubin
RBC --> Hemoglobin --> globin --> aa
Hb --> heme --> biliverdin --> unconjugated bilirubin
1. unconjugated bilirubin transported in bloodstream bound to albumin
2. liver takes up bilirubin by carrier-mediated endocytosis and binds to cytoplasmic proteins (glutathione transferase and protein Y) making it water soluble --> cannot leave back into blood
3. conjugated bilirubin secreted into biliary tree by active transport through multi drug resistant like protein. RLS
4. 3 possibilities
a) some fat soluble bilirubin have to be reabsorbed, but most is oxidised into urobilinogens by flora.
b) colourless urobilinogens metabolised into brown stercobilin and excreted in faeces.
c) some reabsorbed urobilinogen are oxidized to yellow urobilin and excreted as urine
594
jaundice
yellow discoloration of the skin and sclera caused by hyperbilirubinemia ie. double the upper limit of 17 mmol/L
595
unconjugated bilirubin transported in bloodstream bound to
albumin
596
liver takes up bilirubin by _______ and binds to cytoplasmic proteins (_______) making it water soluble --> cannot leave back into blood
carrier-mediated endocytosis
| glutathione transferase and protein Y
597
conjugated bilirubin secreted into biliary tree by _____ through multi drug resistant like protein. RLS
active transport
598
some fat soluble bilirubin have to be reabsorbed, but most is oxidised into _____ by ____.
colourless urobilinogens metabolised into brown _____ and excreted in faeces.
some reabsorbed urobilinogen are oxidized to ____ and excreted as urine
urobilinogens
flora
stercobilin
yellow urobilin
599
yellow discoloration of the skin and sclera
jaundice
600
types of jaundice
1. pre-hepatic
breakdown of RBC excess uptake --> hemolytic jaundice
this can be due to hemolytic diseases, sickle cell anemia or leakage outside vessels
this creates excess bilirubin circulating in blood.
conjugated bilirubin in normal amounts since liver is still functional
no urine bilirubin
increase unconjugated bilirubin in the blood
2. intrahepatic
bilirubin cannot be taken up, conjugated and/or excreted because hepatocytes are damaged --> hepatocellular jaundice
usually accompanied by excess AST and ACT (markers or liver function)
increase conjugated bilirubin
increased ALT or AST
has urine bilirubin (abnormal)
```
3.posthepatic
obstructed biliary flow - conjugated bilirubin regurgitation back into systemic circulation --> obstructive jaundice
patients have pale stools (no stercobilin) and dark urine (excess conjugated bilirubin)
increase conjugated bilirubin
increase ALP
has urine bilirubin (dark)
no stercobilin
no urine urobilinogen
```
601
Newborn jaundice
unconjugated hyperbilirubinemia (prehepatic) is caused by immature/ impaired uptake of the lover
this is due to enzymes of the liver only start to work after birth
therefore it usually resolves itself
treatment - phototherapy or phenobarbitone
602
phototherapy
converts bilirubin to a water soluble non toxic form
603
phenobarbitone
usually given to the mother prior to labour to induce UDP glucuronyl transferase
604
gilbert's syndrome
prehepatic
mild unconjugated hyperbilirubinemia
correlated with fasting or illness caused by reduced activity of UDP glucuronyl transferase
treated by phenobarbitone
605
crigler syndrome
*mutation
606
dubin johnson and rotor's syndrome
conjugated hyperbilirubinemia
impaired biliary secretion
transport defect between liver and biliary tree (RLS) at. the multidrug resistant like protein
607
pre-hepatic
breakdown of RBC excess uptake --> _____
this can be due to hemolytic diseases, sickle cell anemia or leakage outside vessels
this creates excess ____ circulating in blood.
conjugated bilirubin in normal amounts since liver is still functional
no ____
increase _____ in the blood
hemolytic jaundice
bilirubin
no urine bilirubin
unconjugated bilirubin
608
intrahepatic
bilirubin cannot be taken up, conjugated and/or excreted because hepatocytes are damaged --> ____
usually accompanied by excess ___ (markers or liver function)
increase ____
increased ____
has ____ (abnormal)
hepatocellular jaundice
AST and ACT
conjugated bilirubin
ALT or AST
urine bilirubin
609
```
posthepatic
____biliary flow - conjugated bilirubin regurgitation back into systemic circulation --> ____
patients have pale stools (no stercobilin) and dark urine (excess conjugated bilirubin)
increase ___
increase ___
has urine bilirubin (dark)
no ____
no ______
```
obstructed biliary flow
obstructive jaundice
conjugated bilirubin
ALP
stercobilin
urine urobilinogen
610
differential diagnosis of jaundice
| conjugated bilirubin
pre - present
intra - increased
post - increased
611
differential diagnosis of jaundice
| ALT or AST
pre - normal
intra - increased
post - normal
612
differential diagnosis of jaundice
| ALP
pre - normal
intra - normal
post - inc
613
differential diagnosis of jaundice
| urine bilirubin
pre - absent
intra - present
post - present
614
differential diagnosis of jaundice
| urine urobilinogen
pre - present
intra - present
post - absent
615
what type of jaundice is:
breakdown of RBC excess uptake --> hemolytic jaundice
this can be due to hemolytic diseases
prehepatic
616
what type of jaundice is:
| bilirubin cannot be taken up, conjugated and/or excreted because hepatocytes are damaged --> hepatocellular jaundice
intrahepatic
617
what type of jaundice is:
| obstructed biliary flow - conjugated bilirubin regurgitation back into systemic circulation --> obstructive jaundice
post hepatic
