Exam 2 master file Flashcards
1
Q
extracellular concentration of calcium
A
Total 2.5 x 10’-3 M; Free 1.2 x 10’-3 M
2
Q
extracellular concentration of phosphate
A
Total 1.00 x 10’-3M;Free 0.85 x 10’-3 M
3
Q
extracellular function of calcium ion
A
bone mineral; blood coagulation; membrane excitability
4
Q
extracellular function of phosphate
A
bone mineral
5
Q
how might anticoagulants work
A
against calcium ion
6
Q
how does calcium ion affect membrane excitability
A
calcium channels, binding proteins, depolarization
7
Q
intracellular calcium concentration
A
very low 10’-7 M
8
Q
intracellular phosphate concentration
A
1.2 x 10’-3 M
9
Q
intracellular calcium ion function
A
neuronal activation; hormone secretion; muscle contraction in all muscle types
10
Q
why is intracellular calcium kept low
A
calcium can activate neurons and cause unwanted muscle contractions if unchecked
11
Q
what is intracellular phosphate role
A
buffering; structure role; higher energy bonds (GTP, ATP); regulation of proteins by phosphorylation
12
Q
where is 99% of calcium ion
A
in bone
13
Q
how is calcium ion found in blood
A
50% is blood bound to albumin and globulins
14
Q
what major hormones regulate Ca2+
A
PTH, vitamin D, and calcitonin
15
Q
Where is calcium from
A
diet; GI tract is major source;
16
Q
how does calcium travel from GI tract
A
half excreted; half absorbed in blood; 10 mmol travel back and forth between blood and bone; 240 mmol are sent from blood to kidney; 233 mmol go back to blood
17
Q
what is grab and release
A
what bone does with calcium from blood; sends it back; in adults it is balanced because there is no bone growth
18
Q
major glands in charge of calcium regulation
A
thyroid and parathyroid
19
Q
cells in thyroid gland
A
follicular and parafollicular cells
20
Q
what is important about parafollicular cells
A
involved in secreting calcitonin; AKA “C-cells”
21
Q
how does parathyroid present
A
at least four of these glands in one person. Tiny, from 30-50 mg. Sometimes parathyroid sits with thymus, which happens during embryogenesis.
22
Q
what is calcitonin
A
a peptide
23
Q
what do calcitonin and PTH have in common
A
a precursor. But then it is cleaved. PTH precursor is made in thyroid. Calcitonin precursor is made in brain.
24
Q
CGRP
A
calcitonin gene related peptide
25
cells of parathyroid
chief cells and oxyphil cells
26
what do chief cells secrete
PTH
27
what is parathyroid related hormone (PTHrP)
a hormone that is a precursor to PTH, related, but PTH is cleaved from PTHrP
28
how does serum calcium affect PTH
if calcium goes up, PTH goes down and vice versa. Inverse relationship.
29
what is calcium sensor
7TM domain
30
7TM domain
large; changes conformation on the basis of calcium levels in serum
31
what does calcium activate if there are high levels of it
phospholipase. Inhibits PTH secretion and synthesis.
32
what does calcium activate if there are low levels of it
adenylate cyclase cyles. Increases PTH secretion and synthesis.
33
How is either calcium pathway chosen
chosen by sensor and G protein has to be chosen that will activate each specific pathway.
34
PTH receptor
G protein linked
35
what binds to PTH receptor
both PTH and PTHrP
36
How does PTH regulate calcium
PTH activates adenylate cyclase, which activates cAMP production in kidney, which causes retention of Ca in distal convoluted tubule and inhibition of phosphate reabsorption in proximal tubule. Clinically, see more cAMP and phosphate in urine.
37
what is source of vitamin D, besides sunlight
diet
38
what is vitamin D
a classical steroid hormone
39
transcalciferin
Vitamin D transporter
40
good source of vitamin D
fish, because they consume plankton
41
why do we need to consume vitamin D in an oil
it is hydrophobic. Will go right through consumer if taken with water.
42
what is VDRE
vitamin D response element
43
where is VDRE
in promoter domain. Receptor binds to the sequences on VDRE, right?
44
How does PTHR activate adenylate cyclase
Gs activates AC
45
how deos PTHR activate phospholipase
Gq
46
target tissue of vitamin D
Gi tract, bone and kidney
47
effects of vitamin D
uptake of calcium in GI tract because vitamin D increases production of calbindin via gene transcription
48
calbindin
protein that binds to calcium in cytoplasm
49
what are the two calcium pathways in GI tract
active and passive
50
active pathway for calcium in GI tract
specialized transporter with pumps pumps calcium into cell. Calcium binds to calbindin, which shuttles it to other side of cell and pushes it out of cell.
51
passive pathway for calcium in GI tract
calcium travels between cells. Works well when there are large amounts of calcium consumed.
52
why might it be good to upregulate active transport of calcium
to prevent osteoporosis
53
how does calcium travel in kidney
similar pathway to GI tract. Reuptake in distal tubule and upregulation of calcium binding protein.
54
what is the calcium depot in the body
bone(storage and relase system)
55
what cells make up bone
osteoblasts, osteocytes, and osteoclasts
56
osteoblast function
secrete osteoid to form bone, calcify, help with remodeling
57
osteocyte function
made from osteoblasts; hardened in mineral; responsible for blood maintenance like toxin removal and nutrient uptake
58
osteoclast function
responsible for bone degradation
59
mesenchymal cells
differentiate and form osteoblasts
60
how do osteoblasts become osteocytes
osteoblasts become trapped in matrix and cant divide
61
how do osteoclasts raise blood calcium levels
they digest bone and release calcium from bone
62
what receptors are on osteoblasts
alkaline phospholypase, PTHR, IGF-1R
63
what do osteoblasts produce
Type 1 collagen and various noncollagenous proteins
64
what are noncollagenous proteins
osteocalcin, osteonectin, osteopontin, bone sialoprotein, osteoprotegerin, macrophage-colony, stimulating factor
65
osteocalcin
regulated by Vitamin D; has high binding affinity to hydroxyapatite Ca5(PO4)3(OH)
66
how do osteocytes work
sit in bone; interact by projections; close to blood vessels; excrete toxins/take up nutrients from blood
67
where are osteoclasts located
in concave ares called resorption cavities or Howship's Lacunae
68
what does osteoclast secrete
protons and lysosomal enzymes that mediate osteolysis
69
what do calcitonin receptors do on osteoclasts
they inhibit degradation of bone
70
Vitamin D formation cycle
start with a cholesterol – 7-dehydrocholesterol/ irradiate with UV light (skin) → one of the rings breaks –> chelecalciferol (vitamin D3) –> suffers 25-hydroxylation in liver –> becomes 25 hydroxychotecalciferol (25-COH)D3 → treated with either 1. hydroxylation or 24. hydroxylation in kidney → becomes 1,25-dyhydroxycholescalciferol or 24,25-dihydroxycholescalciferol
71
mechanism of vitamin D in target cells
enters nucleus → in nucleus is VDRE, TATA and ATG → at VDRE is bound heterodimer RXR/VDR (coinhibitors are available) → D binds to its receptor on VDRE → string of coactivators complex binds to D and connects it to RNA polymerase II on TATA box(initiation complex)→ transcribes mRNA –> ATG is methionine start codon, which waits in nucleus
72
how do osteoclasts form? What is their function?
fusion of macrophages to form large multinucleated cells. They break down bone matrix.
73
where do osteoblasts come from?
from mesenchymal cells. Make protein matrix -osteoid and calcification hydroxyapatite
74
how do osteocytes form
osteoblasts trapped in matrix. Concerned with bone maintenance.
75
what parts of osteocytes do the work
canaliculi and gap junctions
76
howship's lacunae
invaginations in bone to which osteoclasts attach and release enzymes and H+ and Cl-
77
what does calcitonin do to bone
it has receptors on osteoclasts and inhibits secretory and digestive properties of osteoclasts
78
how do osteoclasts work
form ruffled border between itself and invagination; pump in Cl- and H+; makes more acidic; lysosomal enzymes
79
how does PTH elevate calcium levels in blood
recruits precursors of macrophages that become osteoclasts; indirectly activates osteoclasts by stimulating osteoblasts; upregulates M-CSF and down regulates osteoprotegerin
80
what does osteoprotegerin do
it blocks RANKL from binding with its receptor on macrophage that will become osteoclast
81
how does M-CSF work
binds with macrophage that becomes osteoclast
82
steps of osteoclast differentiation
first, monocyte; second, becomes macrophage and binds M-CSF, which makes it express RANK receptor; third, binds RANKL and is bound to osteoblast; fourth; disassociates from osteoblast but is inactive; fifth, becomes inactive when ruffle forms and and sealing zone form
83
what is alpha v beta 3 integrin
binds to osteoclasts to form sealing zone
84
How does vitamin D affect calcium ion?
Vitamin D increases Ca; it increases Ca ion transport in intestine and kidney by upregulating transcription and translation of calcium binding protein; 2. regulates osteoclast activity in the bone
85
How does PTH regulate calcium
1. increases retention of calcium by kidney and decreases retention of phosphate 2. increases production of calcitriol (active Vitamin D) by kidney 3. osteoclast upregulation, albeit indirectly
86
how does calcitonin work
calcitonin decreases Ca 1. direct inhibition of osteoclast activity in bone 2. increased loss of calcium and phosphate in the kidney filtrate
87
how does prostaglandin E2 affect calcium
increases osteoclast activity
88
what does mechanical stress do
signals need for bone remodeling
89
what does thyroid do to calcium
stimulates osteoclast activity
90
how does bone immobilization affect calcium homeostasis
it increases bone resorption and decreases bone formation ; it increases serum Ca, which decreases PTH. Both increase urine Ca. Decrease in PTH causes decrease Vitamin D, which causes decrease in intestinal calcium absorption
91
how does exercise affect calcium homeostasis
it decreases bone resorption and increases bone formation; it decreases serum Ca, which increases PTH; both lead to decrease in urine Ca. Increase in PTH causes increase in vitamin D; which causes increase in intestinal Ca absorption
92
growth hormone and calcium
mechanism: signals somatomedin C (IGF-1) release from liver; effect: increases bone and cartilage growth
93
thyroid hormones and ca
mechanism: secretions from thyroid gland follicular cell; increases bone and cartilage growth
94
PTH
low blood ca signals relase from parathyroid gland; PTH signals osteoblasts to stimulate osteoclast activity; stimulates osteoclast line development from CFU-GM and bone resporptive activity; inhibits alkaline phosphatase of osteoblast
95
calcitonin
high blood ca signals thyroid c-cell to secrete it; directly inhibits osteoclasts
96
sex hormones
estradiol and testosterone affect cartilage and bone growth; complex actions: stimulate bone growth; leads to closing of growth plate; too much; dwarfism, too little: gigantism, osteoporosis
97
vitamin A
binds to receptors on osteoclasts and releases proteases from chondrocytes; signals bone resorption; signals cartilage resorption
98
vitamin C
cofactor for proline hydroxylase in collagen synthesis; supports collagen formation
99
vitamin D
stimulates ca uptake from gut; stimulates production of osteonectin by osteoblast; stimulates osteoclast development from CFU-MG stem cell; supports mineralization of bone and cartilage; stimulates bone turnover
100
bone growth promoters
insulin, somatomedins, vitamin K
101
bone grrowth inhibitors
sglucocorticoids
102
how do PTH, vitamin D and FGF23 interact
PTH to kidney; upregulate vitamin D; Vitamin D to PT gland; down regualte PTH; vitamin D to bone; upregulate FGF23; bone to kidney, down regulate vitamin D
103
integrated response to hypocalcemia
four responses: calcium sensor taks to PT gland; increase PTH; increase D; increase gut absorption; calcium sensor talks to thyroid c-cells – decrease calcitonin – increase bone resorption (PTH does this as well); ca sensor talks to kidney – increase renal ca absorption (PTH) and decrease urinary ca excretion; renal ca filtration decreases, which decreases ca in urine
104
integrated response to hypercalcemia
foru responses: calcium sensor talks to PT gland – down PTH – down D-down gut absorption; sensor talks to c-cells – up calcitonin – down bown resporption (PTH as well causes this); sensor talks to kidney – down renal ca reabsorption – increase ca in urine – up renal ca filtration, which increases ca urine
105
how does vitamin D affect bone, kidney, gut, blood calcium
bone: up o/c activity, up bone resorption; kidney: up ca reabsorption, up phosphate reabsorption; gut: up calcium absorption, up phosphate absorption; blood: up calcium and phosphate
106
how does PTH affect bone, kidney, gut, blood calcium
bone: down o/b activity, up bone resorption; kidney – up 1alpha hydroxylase synthesis, up ca reabsorption, down phosphate reabsorption; gut – up ca absorption, up phosphate absorption by indirect action only; blood – up ca and down phosphate
107
how does calcitonin affect bone, kidney, gut, blood calcium
bone: down o/c activity, down bone res.; kidney – down ca reab, down p reab; gut – nothing; blood – down ca and p
108
symptoms of hypocalcemia 4
muscle cramps, numbness, parasthesia, mood swings and depression
109
signs of hypoclacemia 5
tetany, carpopedal spasm, neuromuscular activity, convulsions, cardiac arrhythmias, cataract
110
symptoms of hypercalcemia 8
bony pain, abdominal pain from peptic ulceration, acute pancreatitis or constipation, anorexia and nausea, thirst and polyuria, muscle weakness, headache and confusion, palpitations through cardiac arrhythmias, tiredness and fatigue
111
signs of hypercalcemia 5
renal stones, bone fractures, convulsions and coma if severe, corneal calcification, hypertension
112
what can cause bone changes by hyperparathyroidism
many tumors secrete PTH or PTHrP and thus cause generalized demineralization as seen in phalanges of the hand
113
rickets and osteomalacia
disorders of mineralization of organic matrix (D deficiency)
114
osteoporosis
metabolic bone disease with decreased bone mass
115
paget's disease
uncontrolled, large osteoclasts cause bone demineralization
116
osteopetrosis
high density bone with occlusion of marrow spaces and subsequent anemia due to lack of osteoclastic activity
117
jensen's disease or metaphysial chondrodysplesia
causes dwarfism due to deficiency in PTH or PTHrP or its respective receptors
118
symptoms of vitamin D deficiency
pains and aches; severe pain, weakness; osteomalacia; bone pains (hips, ribs, feet, pelvis and thighs)
119
adult vitamin d deficiency symptoms
poor immune system, osteoporosis, mood changes, heart problems and high BP, chronic diseases like crohn's disease and MS, dental problems like gum disease, asthma, bone disease development called osteomalacia
120
How is energy stored in body?
as glycogen and fat
121
how often does fuel metabolism change
several times a day, between catabolic and anabolic phases
122
how are higher brain centers stimulated to influence the gut
taste, smell, sight, thought, etc.
123
What does higher brain send signals to
hypothalamus
124
what does hypothalamus send signals to?
it sends signals back to higher brain and it sends hunger or satiety signals to the gut
125
what signals does the gut send?
the gut stimulates the vagus (SNS) catabolic process and releases CCK in the short term. In the long term, the gut releases hormones that are substrates to the pancreas, which in turn produce insulin, which helps build WAT, and which releases leptin, which also stimulates the SNS anabolic pathway
126
what signals does the SNS send?
it signals the pancreas to produce insulin, which help add WAT and leptin. It also stimulates BAT and heat production.
127
catabolism
tears down molecules
128
anabolism
builds up molecules
129
what makes up the oral cavity? What is it responsible for?
mouth and pharynx, salivary glands; chewing begins, initiation of swallowing
130
what are the exocrine secretions of the salivary glands
salt and water – moisten food; mucus – lubrication; amylase – polysaccharide-digesting enzyme
131
what is role of esophagus
moves food to stomach by peristaltic waves
132
what are esophagus exocrine secretions
mucus for lubrication
133
role of stomach
store, mix, dissolve and continue digestion of food; regulates emptying of dissolved food into small intestine
134
exocrine secretions of stomach
HCL – solubilization of food particles, kill microbes, activation of pepsinogens to pepsins; Pepsins – protein-digesting enzyme; mucus – lubricate and protect epithelial surface
135
role of pancreas
secretion of enzymes and bicarbonate; also has nondigestive endocrine functions
136
exocrine secretions of pancreas
Enzymes – digest carbs, fats, proteins and nucleic acids; bicarbonate – neutralize HCL entering small intestine from stomach
137
liver role
secretion of bile; many other nondigestive functions
138
exocrine secretions of liver
bile salts – solubilize water – insoluble fats; bicarb – neutralize HCL entering small intestine from stomach
139
role of gallbladder
store and concentrate bile between meals
140
role of small intestine
digestion and absorption of most substances, mixing and propulsion of contents
141
exocrine secretions of small intestine
Enzymes – food digestion; salt and water – maintain fluidity of luminal contents; mucus - lubricataion
142
role of large intestine
storage and concentration of undigested matter; absorption of salt and water; mixing and propulsion of contents; defecation
143
exocrine secretions of large intestine
lubrication
144
anatomical features of gut in order from inside to out
lumen, mucosa, submucosa, submucosal nerve plexus, circular muscle, myenteric plexus, longitudinal muscle, serosa. There is sympathetic and parasympathetic input to gut
145
will myenteric plexus move on its own
it is autonomic; will contract without attachment to body. It is a network of mesh.
146
how do enteroendocrine cells present in gut
they are present in most of GI tract distributed as single cells throughout gastrointestinal epithelium
147
largest endocrine “organ”
enteroendocrine cells
148
does enteroendocrine cell reach epithelial surface
no
149
what are the two types of enteroendrocrine cells
lingual taste-receptor cell and intestinal enteroendocrine cell
150
what is ligand that signals enteroendocrine cells
food
151
How does a lingual taste receptor cell work
G protein activates phospholipase Cbeta2; which makes IP3, which increases Ca2+ in cytoplasm, which causes release of neurotransmitters that stimulate afferent nerve
152
what three channels exist on lingual taste receptor
Sodium /transient receptor potential channels' de;ayed-rectifying K+ channels; calcium voltage gated channels
153
how does intestinal enteroendocrine cell work
via nutrient ligand, binds to receptor, activates Galpha protein that activates phospholipase, which synthesizes IP3, increases intracellular calcium, and secretes GLP1 into bloodstream and vagal or spinal nerve
154
what channels live on intestinal enteroendocrine cell
sodium/TRPMS
155
model to increase ghrelin secretion
bitter tastants bind to taste receptors on ghrelin cell or on the brush cells in the GI tract, and couple via alpha-gustducin to increase ghrelin secretion
156
what does increased ghrelin secretion result in
short term increase in food intake and accelerated grastric emptying; followed by a prolonged decrease in food intake
157
what does decrease in food intake correlate with
delay in grastric emptying
158
what does alpha-gustducin do?
it is involved in sensing the medium chain fatty acid (MCFA) octanoic acid in the diet
159
what is octanoic acid necessary for in diet
the octanoylation of ghrelin
160
what receptor may play a role in the lipid sensing cascase in ghrelin-producing cells
GPR120
161
what two hormones are produced in the pyloric antrum?
gastrin and glucagon
162
gastrin function
stimulates release of HCL and pepsinogen
163
glucogen function
promotes conversion of glycogen to glucose in the liver
164
what four hormones are produced in the duodenum and jejunum?
cck, gastric inhibitory peptide, motilin, and secretin
165
cholecystokinin
stimulates pancreatic enzyme release and elicits gallbladder contraction
166
gastric inhibitory peptide
stimulates insulin secretion
167
motilin
stimulates gastrointestinal motility
168
secretin
stimulates bicarbonate and water secretion by pancreatic duct cells
169
what hormone does the ileum produce?
neurotensin
170
neurotensin
inhibits GI motility
171
what hormone does large intestine make?
glicentin
172
glicentin
promotes conversion of glycogen to glucose in liver
173
what hormones are produced in stomach, small intestine and large intestine?
somatosatin, serotonin, substance P
174
somatostatin
inhibits local secretion of gastrin, motilin, secretin, and gastric inhibitory peptide + other actions
175
serotonin
stimulates gastrointestinal motility
176
substance P
stimulates intestinal motility
177
where is gastrin released in large intestine? By when does it diminish?
antrum/ ileum
178
order of large intestine parts
fundus, antrum, duodenum, jejunum, ileum, colon
179
where is CCK release in large intestine? By where does it diminish?
duodenum/colon
180
where is secretin released in large intestine? By where does diminish?
duodenum/colon
181
where is GIP secreted in large intestine? By where does it diminish?
duodenum/ileum
182
Are VIP, Motilin or somatostatin secreted in large intestine?
no, but they are present still
183
what stimuli in cephalic phase control HCL secretion during a meal? What pathway is used?
sight, smell, taste, chewing ; parasympathetic nerves to ENS
184
what stimuli in gastric phase control HCL secretion during a meal? What pathway is used?
distension, increase in peptides, decrease in proton concentration; long and short neural reflexes and direct stimulation of gastrin secretion
185
what stimuli in intestinal phase control HCL secretion during a meal? What pathway is used?
distension, increase in proton concentration, increase in osmolarity, increase in nutrient concentrations; long and short neural reflexes; secretin, CCK, and other duodenal hormones
186
three phases of digestion
cephalic, gastric and intestinal
187
what sphincter is next to esophagus at entrance to stomach
cardiac sphincter
188
what sphincter is at end of stomach
pyloric sphincter
189
layers of stomach wall from luminal to basolateral
glands that secreted gastric juice, gastric glands, circular muscle, longitudinal muscle
190
through what is gastric released into lumen
the gastric fundic region
191
what makes up gastric fundic region, from luminal to basolateral
pit, isthmus, neck, and base
192
what cells line the gastric fundic region?
mucous neck cells (in neck), parietal cells, enteroendocrine cells, chief (zymogenic cells)
193
what are the two secretory cells of the stomach
chief cell and parietal cell
194
what makes up inside of chief cell?
zymogen granules, and extensive rER
195
what makes up inside of parietal cell?
tobulovesicular system, intracellular calaliculus, few ribosomes and lysosomes
196
what does chief cell produce?
precursor enzyme of the gastric secretion; pepsinogen and lipase
197
what does parietal cell produce?
HCL and intrinsic factor for vitamin B12
198
what is at luminal side of both chief and parietal cells
junctional complexes
199
what three receptors does parietal cell have?
histamine H2, acetylcholine, and gastrin
200
what secretes gastrin? How does it get to parietal cell?
G cell. Through the bloodstream.
201
what secretes histamine?
ECL cell
202
What stimulates G cell to secrete gastrin?
vagus nerve stimulates post synaptic neuron, which releases gastrin releasing peptide
203
what stimulates ECL cell to release histamine?
postganglionic cholinergic nerve releases neurotransmitters that bind with receptor on ECL cell
204
what secretes acetylcholine?
a neuron
205
What hormones regulate the parietal cell?
gastrin, histamine, acetylcholine, somatostatin, gastrin releasing peptide
206
how is acetylcholine a major secretagogue?
it stimulates secretion of pepsinogen by chief cells of stomach
207
is gastrin an important secretagogue
it is only effective in vitro and at high concentration
208
what kind of secretory cells do pancreas have?
exocrine and endocrine
209
which pancreatic cells secrete enzymes?
exocrine cells
210
which pancreatic cells secrete bicarbonate?
duct cells
211
what runs along length of pancreas
pancreatic duct
212
what role do pancreas play
main digestive gland in our body
213
what enzymes do the pancreas secrete?
trypsin, chymotrypsin, steapsin, carboxypeptidase, elastases, nucleases, and pancreatic amylase
214
trypsin
protease that cleaves proteins at the basic amino acids
215
chymotrypsin
protease that cleaves proteins at the aromatic amino acids
216
steapsin
degrades triglycerides into fatty acids and glycerol
217
carboxypeptidase
protease that takes off the terminal acid group from a protein
218
elastase
degrades the protein elastin and some other proteins
219
nucleases
degrade nucleic acids, like DNAase and RNAase
220
pancreatic amylase
degrades starch, glycogen and most other carbohydrates
221
bicarb regulation cycle
increase in acid from stomach; increase in secretin secretion in small intestine; increase in plasma secretin; the Panceas increase bicarb secretion, which increases flow of bicarb into small intestine, which neutralizes the intestinal acid put there by stomach. Once pH goes up, this provides negative feedback to small intestine's secretin secretion.
222
fatty acid and amino acid digestion cycle between SI and pancreas
increase in intestinal fatty acids and amino acids; increase in CCK secretion in small intestine; increase in plasma CCK; stimulates pancreas to increase enzyme secretion; increases flow of enzymes into small intestine, which leads to increase in digestion of fats and proteins in SI
223
what part of SI is ileum?
Last part before colon
224
portal vein flows from small intestine to?
liver
225
bile flows from and to?
liver and gallbladder to small intestine
226
what are six main ingredients of bile?
bile salts; lecithin; bicarb ions and other salts; cholesterol; bile pigments and small amounts of other metabolic end-products; protein (IgA) and peptides, and trace metals
227
how do gallstones form?
when concentration of cholesterol in the bile becomes high in relation ot the concentrations of phospholipids and bile salts, cholesterol crystallizes out of solution and causes gallstones
228
enterohepatic circulation of bile salts
bile salts are secreted into bile and enter the duodenum through the common bile duct. Bile salts are reabsorbed from the intestinal lumen into hepatic protal blood. The liver reclaims bile salts from hepatic portal blood.
229
what is preprograstrin
precursor to gastrin
230
what do the structures of gastrin and cck both contain
sulfated tyrosine residue
231
which adiposity signals work straight with hypothalamus (3)
adiponectin, insulin, and leptin
232
Which gut hormones act directly with hypothalamus (3)
PYY, OXM, Ghrelin
233
Which gut hormones act directly with brainstem?
PP, GLP-1, CCK
234
which gut hormones and adipose signals influence vagus?
adiposity signals: leptin; gut: ghrelin, PP, GLP-1, and CCK
235
what does antral mucosa secrete?
gastrin
236
what do pancreas secrete?
insulin, glucagon, somatostatin, pancreatic polypeptide
237
what does upper small intestine secrete?
secretin, CCK, GDIP, motilin
238
what does lower small intestine secrete?
neurotensin, enteroglucagon
239
what do pancreatic islets of langerhans secrete?
insulin, glucagon, and somatostatin
240
what do pancreatic endocrine cells secrete?
pancreatic polypeptides
241
role of CCK in digestion
slows down emptying of the stomach by acting on pyloric sphincter; stimulates bile release from the galbladder and the secretion of pancreatic enzymes
242
role of secretin in digestion
stimulates pancreatic bicarb secretion; enhances insulin secretion by B cells of the islets of langerhans
243
role of gastrin in digestion
stimulates HCL secretion in parietal cells; stimulates insulin secretion by B cells of islets of langerhans; stimulates gastric motility and growth of mucosal cell
244
digestion
breaking proteins, fats and carbs into absorbable units (principally in small intestine)
245
absorption
products of digestion and vitamins, minerals and water cross the mucosa and enter lymph or blood
246
how do mixed amino acids reach the liver?
via the portal vein
247
what are branched amino acids used for?
protein synthesis under influence of insulin
248
how are amino acids and di and tripeptides absorbed?
across symporter channels together with Na+. The transport is active.
249
where does protein digestion start?
in the stomach, in the presence of pepsin.
250
what is pepsin derived from?
precursor pepsinogen secreted by chief cells
251
where does pepsin activity end?
in alkaline environment of duodenum.
252
what pancreatic proteases continue proteolysis?
endopeptidases and exopeptidases
253
what activates trypsinogen? Where?
enterokinase turns trypsinogen to trypsin on the microvilli. Trypsin in turn activates the bulk of trypsinogen.
254
what activates chymotrypsinogen and proelastase?
chymotrypsin and elastase, respectively
255
what are carboxypepsidasea A and B derived from?
procarboxypeptidase A and B precursors
256
in what does trypsin play a significant role?
it activates and inactivates pancreatic proenzymes.
257
how are tripeptides in cytosol digested?
by cytoplasmic peptidases into amino acids
258
what is daily protein requirement for adults?
0.8 g/kg body weight. Higher in pregnant women, postsurgical patients and athletes.
259
why must nine essential amino acids be in diet?
because body cannot synthesize them.
260
in what two ways does glucose from diet enter hepatic glycogen?
a. 50% glycogen formed from ingestd glucose directly, without degradation; remainder is converted to lactate in peripheral and splanchnic tissues
261
how is glucose converted to lactate in peripheral and splanchnic tissues?
15-20% of glucose converted to lactate in subcutaneous adipose tissue and CNS and RBC; lactate returns to liver and is coverted to G-6-phosphate via gluconeogenesis; lactate also from intestinal metabolism of either circulating or newly absorbed glucose.
262
what are the main dietary carbs?
starch, sucrose, lactose and maltose
263
starch?
amylose and amylopectin
264
sucrose?
glucose, fructose disaccharide
265
lactose?
Galactose-glucose disaccharide
266
maltose?
glucose dimer
267
what initiates digestion of starch?
salivary alpha-amylase in the mouth
268
what completes starch digestion?
pancreatic alpha-amylase in small intestine
269
oligosaccharidases
(sucrase, lactase, isomaltase), hydrolyze major dietary sugars; present in PM of microvilli
270
why is cellulose not digested by humans?
cellulase is not present. Cellulose accounts for undigested dietary fiber.
271
what is bile salt?
glycocholic acid
272
what is fat emulsified by?
bile salts and phospholipids
273
what is emulsification?
fat globule and bile salt and phospholipid
274
what do fat droplets become with bile salt and phospholipids?
emulsion droplets
275
add bile salts and pancreatic lipase to emulsion droplets and get?
micelles
276
what happens to emulsion micelles once they are formed?
they become free molecules of fatty acids and monoglycerides that can diffuse through lipid bilayer. They are treated by triglyceride synthetic enzymes in endoplasmic reticulum and become chylomicrons
277
chylomicron
droplets of triglyceride enclosed by membrane from the endoplasmic reticulum
278
where are lipids stored?
adipose tissue
279
what is the purpose of adipose tissue?
adaptation to famine
280
how do lipids travel in circulation?
dietary lipids cross through intestinal cell; become chylomicrons; enter capillaries; are treated by lipoprotein lipase; chylomicron remnants go to liver and are received by remnant receptors
281
what induces the phosphorylation of lipase?
epi, glucagon and ACTH
282
what does phosphorylation of lipase result in?
mobilization of triglyceride pool/ lypolytic effect
283
what inhibits lipase activity?
insulin and prostaglandins
284
what does lipase inhibition cause?
lipid storage, or antilypolytic effect
285
two clinical conditions associated with adipose tissue
obesity and diabetes
286
leptin is produced by?
white adipose tissue
287
leptin provides what?
information about fat mass and nutritional status to neural centers regulating appetite, energy balance and feeding
288
GLUT-4
glucose transporter protein; produced by adipocyte; facilitates entrance of glucose to the cell
289
lipoprotein lipase synthesized by? Transferred to?
synthesized by adipose cell and transferred to endothelial cell
290
catabolism: how does liver produce glucose?
via glycogen breakdown and via gluconeogenesis
291
what is glucose preserved for?
CNS
292
what do tissues besides CNS preferentially use for energy?
long chain fatty acids and their derivative products – ketone bodies
293
what can brain also use, besides glucose
ketones
294
what does lipolysis release?
glycerol
295
where does pyruvate lactate come from?
muscle glycogen
296
where do amino acids come from?
proteolysis
297
what are three additional gluconeogenesis substrates?
glycerol, pyruvate/lactate, amino acids
298
where do hunger and satiety originate?
from afferent neuronal and humoral signals from the GI tract, adipose tissue, and other peripheral organs to the brain
299
from where do hypothalamus and brainstem receive signals to coordinate feeding and metabolic adaptations?
nutrients, GI hormones, adipokines, and vagal afferents
300
when are peripheral stimuli and inhibitors to digestion released?
in anticipation or response to food
301
what can peripheral stimuli and inhibitors cross?
blood brain barrier
302
what is role of peripheral stimuli and inhibitors?
activate/release/synthesize central factors in the hypothalamus that either increase or decrease subsequent food intake
303
where do executive functions originate?
frontal cortex
304
central inhibitors (5)
POMC, CART, CCK, NE, CRH
305
central stimuli (3)
NYY, orexin-A, cannabinoids
306
when stomach releases ghrelin and cortisol, what do they stimulate?
they cross the BBB and stimulate NYY, orexin-A and cannabinoids
307
list peripheral inhibitors (7)
glucose/AA/FFA, CCK, PYY, insulin, leptin
308
how is ghrelin initially synthesized?
as a preprohormone
309
how is ghrelin processed?
proteolytically processed to yield 28 aa peptide
310
when is ghrelin produced and secreted?
by stomach as early response to food
311
in the brain, what is source of ghrelin?
hypothalamus
312
where else, other than hypothalamus and stomach, is ghrelin made?
placenta, kidney and pituitary gland
313
What 3 major regions of brain does ghrelin stimulate?
hindbrain, hypothalamus, mesolimbic reward system in midbrain
314
role of hindbrain
controls automatic processes
315
role of hypothalamus
regulates metabolism
316
when does ghrelin spike?
before routine meal times.
317
when does ghrelin spike for grazing animals?
they have little spikes all day
318
from what are glucagon, oxyntomodulin, NPGF and glicentin derived?
from a larger, common precursor that has 158 aa
319
what does oxyntomodulin do?
it acts to suppress appetite
320
what were results of parabiosis study of Ob/Ob and Db/Db mice?
Ob and WT – slimmer OB, normal WT; Db and WT – normal Db and slimmer WT; Ob and Db – slimmer Ob and normal Db.
321
how big is leptin?
16 Kda protein hormone
322
where is leptin made?
synthesized and secreted by adipose tissue and the placenta
323
of what gene is leptin a product?
Ob gene, on chromosome 7q31.3-32
324
what is main target of leptin?
hypothalamus
325
what kind of receptor does leptin have?
cytokine receptor group of cell surface receptors
326
what is intracellular signaling apparatus of leptin receptor?
JAK-STAT
327
leptin binding protein
soluble isoform of ectodomain of leptin receptor forms a binding protein in circulation
328
main actions of leptin
suppress appetite; increases energy expenditure
329
leptin and fasting
plasma leptin is very low, so stored energy is conserved
330
nonfasting and leptin
circulating leptin increases with adiposity
331
rhythm of circulating leptin
exhibits circadian rhythm; highest around midnight with nadir around middday
332
relative levels of plasma leptin throughout life in newborn, childhood, puberty and adulthood?
Newborn – high; childhood – low; puberty – leptin increases early in puberty. In boys, increase is only transient. In girls, sustained. ; adulthood – leptin higher in women than men
333
how do environment and lifestyle influence food intake and energy expenditure in brain?
cognition; reward; choice; mood; stress
334
how does brain respond to environmental stimuli?
energy intake or expenditure
335
cycle of energy intake?
GI, liver, to adipose tissue and muscle tissue, where there is nutritional partitioning
336
what three things influence individual predisposition to digestion?
genetics, early life events and epigenetics
337
what neurotransmitters decrease food intake (3)
Norepi – Beta receptor; dopamine; serotonin
338
what hypothalamic peptides decrease food intake (4)
Cordicotropin-releasing factor (CRF); urocortin; glucagon-like peptide I (GLP-I); cholecystokinin (CCK)
339
peripheral factors that decrease food intake? 3
leptin, CCK, and insulin
340
when are peripheral factor effects observed, that decrease food intake?
Leptin – long term signal; CCK – meal-related signal; insulin – effect observed after central administration
341
central factors that increase food intake (6)
Norepi – alpha receptor; neuropeptide Y (NPY); melanin concentrating hormone (MCH); galanin; growth hormone-releasing hormone (GHRH); opioid peptides
342
pereipheral factor that increases food intake (1)
hypoglycemia
343
pathologies associated with food intake
obesity, anorexia nervosa, bulimia nervosa
344
what fuels anabolism?
diet
345
what processes happen during anabolism?
glycogen, triglyceride and protein synthesis
346
what is anabolism?
making and storing compounds
347
hormone profile of anabolism
insulin increase, glucagon decrease, GI peptide increase, leptin increase
348
what fuels catabolism?
glycogen, fat deposits, muscle protein
349
what processes happen during catabolism?
glycogenolysis, gluconeogenesis, lypolysis, ketogenesis, proteolysis
350
catabolism hormone profile
insulin decrease, glugacon increase, catecholamines increase
351
what two processes make glucose in liver?
glycogenolysis and gluconeogenesis
352
what do muscles feed into gluconeogenesis?
amino acids and glycogen
353
what does adipose tissue contribute to liver?
fatty acids
354
what does liver do with fatty acids?
ketogenesis
355
what is the result of ketogenesis?
ketones headed for nonCNS and CNS
356
what is destination of glucose?
CNS
357
What fuels CNS?
glucose
358
most glucose transporters work by
facilitated diffusion
359
why does glucose concentration outside of brain need to remain high?
because of concentration gradient needed for facilitated diffusion into brain
360
what can be used by brain besides glucose
ketones
361
name three substrates for glucogenesis
glycerol from lipolysis, pyruvate-lactate from muscle glycogen, amino acids from proteolysis
362
where does glucose go once past the gut? (postmeal)
blood
363
from blood where does glucose go?
muscle, liver, adipose tissue and nerve and other tissues
364
what does blood glucose become in muscle?
glycogen
365
what does blood glucose become in liver?
glycogen and triglycerides
366
what does blood glucose become adipose tissue?
triglycerides
367
how does glucose get to blood during fasting?
muscle and adipose tissue send amino acids, glycogen, and fatty acids to liver to become glucose through gluconeogenesis
368
what do fatty acids become in liver?
ketones
369
three types of cells in pancreas islets of langerhans
beta, alpha and delta cells
370
beta cells
synthesis and secretion of insulin. Are in center of islet.
371
alpha cells
25% of cell content in islets – make glucagon, periphery of islet
372
delta cells
somatostatin producers in periphery of islet
373
how are pancreas vascularized?
arterioles feed into center of islet so beta cells get exposed to high glucose concentration. Arterioles supply capillaries that drain into venules that drain out of islets.
374
how are cells connected to one another in islets of langerhans?
by gap junctions so they can signal each other
375
acinear cells
smaller than islet of langerhans cells (release into duodenum?)
376
what is inside beta cells
high density of granules with insulin inside
377
what increases insulin secretion?
amino acids, raised blood glucose, glucagon, gastrin, secretin, cck, GIP, sympathetic innervation (alpha-receptors), parasympathetic (cholinergic) innervation
378
GIP
glucose dependent insulinotrophic peptide
379
what is insulin secretion decreased by?
somatostatin, blood glucose, sympathetic innervation of beta receptros , stress (exercise, hypoxia, hypothermia, surgery, severe burns)
380
how is response to orally administered glucose different from that delivered via IV?
greater insulin stimulating effect.
381
how is response to orally administered aa different from that delivered via IV?
greater insulin stimulating effect.
382
do peptides secreted by GI endo cells stimulate insulin secretion?
yes
383
how does GLP-1 regulate insulin secretion and blood glucose levels?
Incretin and GLP-1 stimulate insulin release and inhibit glucagon release, both of which lower blood glucose
384
what inactivates GLP-1?
DPP-4 enzyme
385
what inhibits DPP-4? To what end?
drugs block DPP-4 and decrease glucose levels in blood
386
where is GLP-1 secreted?
L-cells of GI
387
how is an increase in blood glucose regulated?
1. release of insulin 2. insulin binds to membrane receptors in liver cells, adipocyte and muscle cells 3. in liver, increase activity of glycogen synthase (stores glucose) and adypocyte and muscle, exocytosis and activation of glucose transporters (so glucose has where to go) 4. removal of glucose from blood and is stored as glycogen
388
hos is decrease in blood glucose regulated?
1. release of glucagon 2. glucagon binds to membrane receptor 3. activation of adenylyl cyclase 4. increase in cAMP, activation of cAMP-dependent kinase 5. activation of glycogen phosphorylase and inhibition of glycogen synthase 6. degradation of glycogen to glucose, release of glucose into blood
389
subcellular sites of insulin biosynthesis in beta cells
1. rough ER 2. microvesicles 3. golgi 4. early granules 5. mature granules 6. plasma membrane
390
proinsulin to insulin process
86 aa proinsulin goes through protease and becomes 21 aa A-chain, 30 aa B-chain and C peptide
391
what happens to glucagon in anticipation of oral glucose load?
its concentration initially increases, but then is suppressed by increase in insulin
392
how does insulin react to oral glucose load?
rise in insulin lags behind glucose peak
393
how does high glucose affect GH release?
high glucose suppresses basal GH release initially, but there is a surge after 2-3 hours. This is a response to falling glucose concentration.
394
how do elevated insulin levels affect lipogenesis?
stimulate lipogenesis because it cases a decrease in circulating free fatty acids
395
what does GH to to free fatty acids?
causes their release from adipose tissue for use by muscle and liver cells
396
How does Glut2 transporter work?
1. glucose enters cell via glut2 transporter 2. glucose metabolism produces ATP as it becomes pyruvate 3. ATP levels increase in cytoplasm and closes K+ channels 4. membrane depolarization follows causing step 5 5. opening of voltage gated Ca2+ channels 6. elevation oin cytosolic Ca2+ stimulates secretion of insulin.
397
how does insulin receptor work?
1. conformation change leads to receptor autophosphorylation and tyrosine phosphorylation of intracellular protein substrates 2. insulin activates 2 main branching pathways
398
what two pathways does insulin receptor stimulate?
Ras-MAP kinase and IRS pathways
399
Ras-MAP kinase pathway
1. receptor binds Shc, which binds Grb2 ans SOS. 2. SOS binds Ras and Ras binds Raf 3. Raf activates MEK. 4 MEK activates Erk1/2, which causes cell proliferation and antiapoptosis
400
what is Ras-MAP kinase pathway known as?
growth signal
401
IRS pathway
actiavates kinase dependent on heterodimeric (p85/p110) p12K (protein kinase B). this modulates enzyme activities that control glucose, lipid and protein metabolism and affect NO generation and apoptosis. Also known as metabolic signal.
402
how does insulin receptor signal transduction lead to metabolic changes
insulin binds and activates protein kinase B. protein kinase B activates Glut4 translocation and inactivates GSK3, which inhibits glycogen synthase
403
what is insulin receptor like?
dimeric receptor tyrosine kinase
404
what are two roles of insulin receptor?
Ras-MAP kinase pathway and glucose levels in circulation regulation
405
What is IR made up of?
2 extracellular alpha subunits that bind insulin and 2 transmembrane beta-subunits that contain tyrosine kinase domain
406
what mediates insulin effects on metabolism?
protein kinase B
407
what does insulin result in with blood glucose?
increase of glucose transport from blood, translocation of glucose transporters to plasma membrane I fat and muscle, activation of glycogen synthase.
408
how does glucose enter intestines and kidney?
secondary active transport with Na+
409
how does insulin stimulate glucose entry into muscle, adipose and other cells?
upregulates no of glucose transporters in cell membrane
410
where is Glut4 stored?
in muscle and adipose cells in vesicles in cytoplasm
411
what happens to glut4 vesicles after insulin binds cell?
vesicles fuse with plasma membrand and increase no. of Glut4 on cell surface
412
how does insulin affect liver catabolic pathways?
inhibits glycogenolysis, conversion of fatty acids and aa to keto acids and conversion of aa to glucose
413
how does insulin affect liver anabolic pathways?
promotes glucose storage as glycogen (induces glucokinase and glycogen synthase, inhibits phosphorylase), increases triglyceride synthesis and VLDL formation
414
how does insulin affect muscle protein synthesis?
increases aa transport, and ribosomal protein synthesis
415
how does insulin affect muscle glycogen synthesis?
increases glucose transport, induces glycogen synthase, inhibits phosphorylase
416
how does insulin affect adipose tissue triglyceride storage?
a. lipoprotein lipase is induced by insulin to hydrolyze triglycerides in circulating lipoproteins for delivery of fatty acids to adipocytes b. glucose transport nto cell provides glycerol phosphate to permit esterification of fatty acids supplied by lipoprotein transport c. intracellular lipase is inhibited by insulin
417
how does insulin affect brain?
decreases appetite. Increases energy expenditure.
418
how does insulin affect K+?
causes K+ to enter cells – lowers extracellular K+ concentration. Infusions of insulin and glucose lower plasma K+ level in normal individuals. Very effective for temporary relief of hyperkalemia in patients with renal failure. Increases activity of Na/K ATPase in cell membrane, so more K+ is pumped into cells
419
how is glycogen synthesized?
UDP-glucose plus glycogen in residues , through glycogen synthase, results in glycogen (n + 1 residues) and UDP
420
how is glycogen degraded?
glycogen (in residues) through glycogen phosphorylate and Pi becomes glucose-1-phosphate and glycogen (n-1 residues)
421
how does increased cAMP regulate glycogen levels?
stimulates glycogen breakdown and inhibits glycogen synthesis. Inactive cAPK phosphorylates GPK, which phosphorylates GP, which breaks down into glycogen (n+1 residues) plues glucose. Inactive cAPK phosphorylates GS
422
how does decreased cAMP regulate glycogen levels?
inhibits glycogen breakdown and stimulates glycogen synthesis. Active PP dephosphorylates GPK and GP and GS, which leads to UDP glucose becoming glycogen and UDP
423
At what plasma glucose level does insulin secretion get inhibited?
Approx 80 mg/dL
424
At what plasma glucose level do glucagon, epi, and GH get secreted?
Approx 68 mg/dL
425
At what plasma glucose level is there cortisol secretion due to stress?
Approximately 55 mg/dL
426
At what plasma glucose level is there cognitive dysfunction?
Approx 50 mg/dL
427
At what plasma glucose level is there a coma?
30 mg/dL
428
At what plasma glucose level are there convulsions?
20 mg/dL
429
At what plasma glucose level is there permanent brain damage or death?
Under 15 mg/dL
430
What is human proglucagon precursor to in alpha cells?
GRPP, glucagon, hexapeptide and major proglucagon segment.
431
What is human proglucagon precursor to in small intestine?
Glincentin, Truncated GLP-1 and GLP-2
432
What is Glincentin a precursor to?
GRPP and Oxyntomodulin
433
What are steps of glucagon/receptor G-alpha-s pathway?
Glucagon binds with G protein 7 transmembrane domain. G alpha-s dissociates from Beta and gamma, loses GDP and gains GTP, and activates adenylate cyclase, which makes cAMP in cytoplasm. cAMP increases active PKA, which increases active phosphorylase kinase, which phosphorylates Phosphorylase, which increases glycogenolysis. Increase in active PKA also uses PGC-1, PEPCK and G-6-Pase to increase gluconeogenesis, which increases glucose.
434
What are steps of glucagon/receptor G-q pathway?
G-q activates phospholipase C, which makes PiP2 and IP3, which leads to release of Ca2+ in cytosol, which leads to decrease in glycolysis and glycogenesis.
435
What are the steps of glycogenolytic response stimulated by glucagon?
Glucagon activates adenylate cyclase, which makes cAMP, which activates phosphorylase kinase, which activates phosphorylase b to make it phosphorylase a, which accelerates the production of glucose-1-phosphate from glycogen.
436
What regulates glycogen mobilization from the liver?
Glucagon
437
By how much does glucagon accelerate production of glucose-1-phosphate from glycogen?
1000 fold
438
is glycogen synthetase active or inactive in the phosphorylated form?
Inactive
439
What does glucagon action on liver or epinephrine action on muscle stimulate?
Adenylate cyclase
440
What kind of proteins are capable of phosphorylating glycogen synthetase?
Two protein kinases. One is cAMP dependent and the other cAMP independent.
441
Glycogen synthetase regulation via glucagon and adreline.
Glucagon acts on liver. Adrenaline acts on muscle. Both hormones stimulate adenylate cyclase. Adenylate cyclase makes cAMP. cAMP activates cAMP-dependent protein kinase, which phosphorylates glycogen synthetase and renders it inactive.
442
Glycogen synthetase regulation via insulin.
Insulin inhibits (somehow) cAMP-independent protein kinase, which makes it stop phosphorylating glycogen synthetase, so glycogen synthetase is activated because it has not be phosphorylated.
443
How does insulin regulate glycogen synthetase via factor Fa?
Insulin activates Fa, which reacts with an inactive form of phosphoprotein phosphatase to produce the active form of the phosphatase. Phosphatase dephosphorylates glycogen synthetase, rendering it active.
444
Percentage of adults in US with diabetes? Prediabetes?
11.3%/ 35%
445
How does diabetes rank as cause of death in the US?
7th leading cause
446
Insulin-dependent diabetes mellitus (IDDM)
Low or absent levels of circulating endogenous insulin; dependent on injected insulin to prevent ketosis and sustain life. Onset predominantly in youth but can occur at any age. Associated with certain HLA and GAD antigens. Abnormal immune response; islet cell antibodies are frequently present at diagnosis.
447
Non-insulin-dependent diabetes mellitus (NIDDM)
Insulin levels may be normal, elevated, or depressed; hyperinsulinemia and insulin resistance characterize most patients and insulinopenia may develop as the disease progresses. Not insulin dependent or ketosis prone under normal circumstances but may require insulin for treatment of hyperglycemia. Onset predominantly after age 40 years but can occur at any age. Approximately 50% of men and 70% of women are obese. Cause probably strongly genetic; 60-90% of monozygotic twins are concordant for NIDDM.
448
Gestational diabetes
Glucose intolerance that has its onset or recognition during pregnancy. Associated with older age, obesity, family history of diabetes. Conveys increased risk for the woman for subsequent progression to NIDDM. Associated with increased risk of macrosomia.
449
Glucose pathway
Diet to intestine to plasma glucose. From blood goes to liver, muscle, adipose, brain and kidney. From kidney, glucose leaves through urine.
450
Glycosuria
Glucose in urine
451
What type of disease is Type 1 diabetes?
An autoimmune disease
452
Pancreas/lymph node Type 1 diabetes pathway
Viral attack on pancreas, which release insulin pieces and other cell protein fragments that are taken to lymph nodes. Autorreactive T cells attack islet cells. Islet cells are killed.
453
What happens to diabetics who have inherited DR3 (but not DR4)?
Tend to develop diabetes earlier in life and have an immune reaction against insulin.
454
What happens to diabetics who inherit both DR3 and DR4?
They develop diabetes at the youngest age and have the highest levels of antibodies against insulin.
455
Risk levels of HLA-DR allele 1-9
DR1 slight risk, DR2 protective, DR3 significant risk, DR4 significant risk, DR5 slight risk, DR6 neutral/protective, DR7 protective/risk in African descent, DR8 neutral/slight risk, DR9 risk in Chinese, Japanese, Korean descent
456
What leads to type 2 diabetes?
Too much food/animal fat, not enough exercise, one set of genes inherited from parents make you hungry, another set of genes cause greater insulin resistance, being overweight, which makes body resistant to insulin, making it produce more
457
How do genes affect pancreas directly in type 2 diabetes?
Make islet cells wear out early and one can’t make enough insulin.
458
What do fatty deposits from being overweight do to pancreas?
Damage islet cells
459
What is the cause of type 2 diabetes, insulin wise?
Body needs more insulin but can’t produce it
460
How does body develop insulin resistance in type 2 diabetes?
Decrease in insulin receptor number, change in receptor signaling (from insulin R to GLUT4), decrease in the glucose transport
461
How does abdominal adipose tissue change in obesity?
Macrophages and other immune cells change in obese fat tissue, and release elevated amounts of cytokines leading to metabolic disease. Immune cells cause low-grade inflammation, insulin resistance, and metabolic disease.
462
How do insulin deficiency and glucagon excess contribute to underutilization of glucose?
Insulin very much. Glucagon zero.
463
How do insulin deficiency and glucagon excess contribute to overproduction of glucose?
Insulin + Glucagon ++++
464
How do insulin deficiency and glucagon excess contribute to increased glycogenolysis?
Insulin + Glucagon ++++
465
How do insulin deficiency and glucagon excess contribute to increased gluconeogenesis?
Insulin + Glucagon ++++
466
How do insulin deficiency and glucagon excess contribute to increased release of aa?
Insulin very much. Glucagon zero.
467
How do insulin deficiency and glucagon excess contribute to increased release of aa?
Insulin very much. Glucagon zero.
468
How do insulin deficiency and glucagon excess contribute to increased lipolysis?
Insulin ++++ Glucagon +
469
How do insulin deficiency and glucagon excess contribute to increased hepatic ketogenesis?
Insulin + Glucagon ++++
470
How does insulin deficiency lead to ketone acidosis?
Increase in lipolysis, increase in plasma free fatty acids, increase in ketone synthesis, increase in plasma ketones, increase in plasma H+ (acidosis), which leads to impaired brain function and death
471
How does insulin deficiency lead to decrease in brain blood flow?
Decrease in glucose uptake by cells, increase in glycogenolysis and gluconeogenesis. Increase in plasma glucose. Increase in renal filtration of glucose and ketones. Osmotic diuresis. Increase in sodium and water excretion. Decrease in plasma volume. Decrease in arterial bp. Decrease in brain blood flow, which leads to impaired brain function and death.
472
How does diabetes affect the vascular system?
Through atherosclerosis and arteriolosclerosis.
473
Atherosclerosis
Of the aorta and large and medium-sized blood vessels leads to myocardial and brain infarctions and gangrene of the lower extremities.
474
Arteriolosclerosis
Thickening of the wall of the arterioles; associated with hypertension
475
How does diabetes affect the bladder?
Urinary bladder neuropathy (alteration in the autonomic nervous system)
476
How does diabetes cause eye complications?
Total blindness. Retinopathy, cataract, glaucoma.
477
Retinopathy
Damage of retina
478
Cataract
Opacity of lens
479
Glaucoma
Impaired drainage of the aqueous humor is frequently observed
480
How does diabetes affect kidneys?
Glomerulosclerosis, aerteriosclerosis, pyelonephritis, and diffuse thickening of the basal lamina of the glomerular capillaries and proliferation of mesangial cells, or Kimmelstiel-Wilson lesion
481
Gangrene
Caused by blood vessel obstruction as a consequence of vascular arteriosclerosis
482
What causes osmotic damage in diabetes?
Increased activity of the sorbitol and glycogenic pathways
483
What do glycosylation reactions in diabetes lead to?
Alterations in the eye and basement membranes of cells, which in turn affect permeability and transport mechanisms
484
What does increase of glycogen in kidney and leucocytes cause?
Osmotic damage
485
What kind of glycosylation of proteins happens in diabetes because of high circulating levels of glucose?
Non-enzymatic glycosylation
486
Which amino acids are primarily glycosylated?
Lysine and valine
487
What damage does diabetes do to eye?
Microaneurysms, “cotton wool” spots, hemorraghes, exudates and abnormal blood vessels.
488
Difference between healthy and diabetic retinal capillaries.
Diabetic retinal capillaries – some are closed off, others form dilated segments “microaneurysms”
489
What happens to basal lamina in diabetic kidney
Thickening
490
What leads to neuropathy in diabetes?
Changes in nerve bundles (NB)
491
Diabetes treatment options
Insulin pump, islet transplantation
492
How does islet transplantation work?
Donor pancreas, isolate islets, use syringe to put islets in portal vein
