GI Flashcards
(280 cards)
1
Q
7 functions the liver performs
A
Carbohydrate, fat, protein, hormone and toxin/drug metabolism
Storage
Bilirubin metaoblism and excretion
2
Q
2 storage spaces of iron in the body?
A
Liver
Reticuloendothelial macrophages
3
Q
What protein is iron carried by in the plasma?
A
Transferrin
4
Q
Where is dietary iron absorbed in the GI tract?
A
Duodenum
5
Q
Where is iron sent to from plasma? What is its role?
A
Muscle cells (plays role in muscle contraction?)
Bone marrow (to form haemoglobin in erythrocytes)
6
Q
Iron loss from…
A
Menstruation
Other blood loss
Desquamation
7
Q
Ferritin structure and location
A
Subunits form a shell around a central core which contains up to 5000 iron atoms
Found in cytoplasm of cells and also in serum
8
Q
Ferritin excess means…
Ferritin deficient means…
A
Could have an excess iron storage disorder
Iron deficiency
9
Q
Vitamins can act as…(3)
A
Gene activators
Coenzymes/cofactors in metabolism
Free-radical scavengers (protects cell from damage caused by free-radicals)
10
Q
2 water soluble vitamins
A
B and C
11
Q
4 fat soluble vitamins
A
A, D, E, K
12
Q
Why do you require more regular intake of water soluble than fat soluble vitamins?
A
Water soluble pass through the body much more readily so you can become deficient in them quicker.
13
Q
Sources of carotenoids and how they produce vitamin A
A
Carrots, tomatoes, spinach
Oxidation of carotenoids then produces retinol (vitamin A)
14
Q
Sources of retinol (vitamin A)
A
cheese, eggs, oily fish
15
Q
3 functions of vitamin A
A
Vision (used to form rhodopsin)
Reproduction (spermatogenesis)
Growth
16
Q
Vitamin A deficiency cause and features
A
Due to fat malabsorption
Blindness/Xerophthalmia
17
Q
Chronic Vit A Excess Symptoms
A
Joint pain, anorexia, hairloss
18
Q
Acute Vit A Excess Symptoms
A
Abdominal pain, severe headaches
19
Q
Carotenemia
A
Reversible yellow pigmentation of skin from risen beta-carotene levels in blood
20
Q
How does sunlight exposure lead to vitamin D production
A
Sunlight stimulates conversion of 7-dehydrocholesterol -> Vitamin D3 which is sent to the liver
21
Q
Vitamin D dietary sources
A
D3 - Fish and meat
D2 - Supplements
22
Q
Why is vitamin D3 transported liver->kidneys?
A
To be converted to the active form of vitamin D3 that can be used by the body
23
Q
3 functions of vitamin D
A
Increased intestinal absorption of calcium
Resorption/formation of bone
Reduces renal calcium excretion
24
Q
Deficiency of vitamin D causes…
A
Demineralisation of bone:
Rickets in children, osteomalacia in adults
25
What carries vitamin K from liver to plasma?
Low density lipoproteins
26
Sources of vitamin K
Synthesised by plants (K1)
Synthesised by humans in intestinal bacteria (K2)
Synthetic vitamin K (K3, K4)
27
Vitamin K functions
Activation of some clotting factors
Necessary for specific liver synthesis of plasma clotting factors
28
Vitamin K deficiency causes...
Haemorrhagic disease of newborn (bleeding from low clotting factors from low vitamin K levels)
29
Excess vitamin K causes...
Red cell fragility (only in synthetic forms)
30
Vitamin C source and functions
How much do adults need a day?
Fruit and veg
Collagen synthesis
Antioxidant
Iron absorption
40mg/day
31
Vitamin E storage, function, and amount needed
Labile and fixed pools in non-adipose cells
Fixed pool in adipose cells
Important antioxidant (protects body against free radicals)
4mg/day in women
3mg/day in men
32
Vitamin E deficiency caused by...
Fat malabsorption
33
Result of vitamin C deficiency/excess
Deficiency - Scurvy (easy bruising, gum disease, hair loss)
Excess - >1g/day = GI side effects
34
How is vitamin B12 protected from stomach acid?
Binds to R protein (released from R protein by pancreatic polypeptide0
35
How is vitamin B12 absorbed?
Binds to intrinsic factor forming IF-B12 which is absorbed in the terminal ileum and stored in the liver
36
Vitamin B12 deficiency causes and symptoms
Pernicious anaemia (autoimmune destruction of IF producing cells in stomach), malabsorption, veganism
Causes peripheral neuropathy
36
Vitamin B12 deficiency causes and symptoms
Pernicious anaemia (autoimmune destruction of IF producing cells in stomach), malabsorption, veganism
Causes peripheral neuropathy
37
When do individuals have higher folate requirements?
Pregnancy
38
What are folate functions?
Acts as a coenzyme in methylation reactions and DNA synthesis
39
Folate deficiency causes and symptoms
Malabsorption, anticonvulsants (interfere with folic acid metabolism)
Can cause macrocytic anaemia and foetal development abnormalities (neural tube defects)
40
What activates the extrinsic pathway of the coagulation cascade?
Contact between FVII and tissue factor
41
Clotting factors produced in the liver
I (Fibrinogen)
II (Prothrombin)
IV
V
VI
VII
42
Performance of clotting pathways measured by...
Prothrombin time (PT) (extrinsic pathway)
Activated partial thromboplastin time (aPTT) (intrinsic pathway)
(prolonged prothrombin time doesn't confirm you have liver disease but shows how well your liver can synthesise things)
43
3 colon functions
Absorption of water and electrolytes
Excretion of waste
Producing vitamins
44
Muscle layers in colon
Continuous circular muscle
3 ribbons longitudinal muscle (taeniae coli)
45
Cells in colon mucosa
Simple columnar epithelium (lots of microvilli)
Goblet cells
46
4 phases of defecation
1) Basal
2) Pre-expulsive
3) Expulsive
4) Termination
47
What occurs in the basal phase of defecation?
Segmental mixing in colon
Tonic contraction of anal sphincter
Contraction of puborectalis (maintaining 90degree anorectal angle)
48
What occurs in the pre-expulsive phase of defecation?
High amplitude contractions of colon (gastro-colic reflex)
Rectum fills causing distension
EAS maintains contraction, IAS reflex relaxation
Puborectalis remains contracted
49
What occurs in the expulsive phase of defecation?
Rectum contracts
IAS, EAS, PR relax along with valsalva manoeuvre / posture aids emptying
50
What occurs in termination phase of defecation?
Traction loss due to sudden EAS contraction (closing reflex)
51
Nerve supply to colon
Intrinsic - ENS (Myenteric Plexus, Submucosal Plexus)
Extrinsic - Parasympathetic and Sympathetic
52
Hard stools caused by...
causing constipation
Opioids, low fluid intake, low fibre
53
How are proteases secreted in stomach?
Chief cells produce pepsinogen
Activated in lumen by pepsin and HCl
54
Where does inactivation of pepsin occur?
In small intestine by bicarbonate secretion increasing pH (irreversible inactivation)
55
Zymogen
Inactive protein precursor of an enzyme (pepsinogen)
56
How is pepsinogen production mediated?
Input from ENS (ACh)
57
Role of pepsin
Breaks down collagen in meat into smaller pieces with greater surface area for digestion
58
Receptive relaxation of body and fundus mediated by...
Parasympathetic nervous system acting on enteric nerve plexuses (nitric oxide and serotonin released by enteric nerves mediates relaxation
59
Any ammonia which evades detoxification as urea can be...
Ammonia + Glutamate -> Glutamine (Glutamine Synthetase)
60
In the glucose alanine cycle, at the muscle, ALT...
transaminates the amino group from glutamate forming a-Ketoglutarate. The amino group gets attached to pyruvate making alanine (the opposite occurs at the liver)
61
Stomach Functions (9)
Store/mix food
Dissolve, continue digestion
Regulate emptying into duodenum (due to its larger volume)
Kill microbes
Secrete proteases
Secrete IF (helps in absorption of vit B12 in terminal ileum)
Activate proteases
Lubrication
Mucosal digestion
62
4 key stomach cell types
Mucous cells
Parietal cells (secrete HCl and IF)
Chief cells (secrete pepsinogen)
Enteroendocrine cells (secrete gastrin)
63
Neural input to stomach supplied primarily by
Vagus nerve
64
How much gastric acid secreted per day in stomach?
Approx 2 litres
65
Arterial supply of foregut, midgut and hindgut
Foregut - coeliac trunk
Midgut - SMA
Hindgut - IMA
66
Symp/Parasymp innervation from ANS of foregut
S: Greater splanchnic nerve (T5/6-T9)
P: Vagus
67
Symp/Parasymp innervation from ANS of midgut
S: Lesser splanchnic nerve (T10-11)
P: Vagus
68
Symp/Parasymp innervation form ANS of hindgut
S: Least splanchnic nerve (T12 +/- L1)
P: Pelvic splanchnics
69
Where is visceral pain felt in foregut?
Epigastric region
70
Where is visceral pain felt in midgut?
Umbilical region
71
Where is visceral pain felt in hindgut?
Suprapubic region
72
Start and end of foregut
Start - Distal oesophagus
End - Halfway along duodenum (1st and 2nd parts of duodenum are foregut)
73
Start and end of midgut
Start - Halfway along duodenum (3rd and 4th parts)
End - First 2/3 of transverse colon
74
Start and end of hindgut
Start - Distal 1/3 transverse colon
End - Upper anal canal
75
Chemical vs Electrical Synapse
Chemical - Neurotransmitters (majority)
Electrical - direct flow of ions (less abundant)
76
Explain chemical synaptic transmission
-Axon potential depolarises synaptic terminal membrane
-Opening of voltage-gated Ca channels = Ca influx
-Ca influx triggers neurotransmitter release
77
Electrical synapse structure
Gap junctions
Channel formed by pores in each membrane
Connexon made up of 6 connexins in a ring which form the pore allowing flow of ions
78
Dendritic spines
Tiny protrusions from dendrites which form functional contact with other axons
ER found within them (to make proteins)
79
Arborisation of neurons
Neurons search for appropriate targets by expanding and/or retracting their axons
80
Oligodendrocytes
Myelinating cells of CNS
81
Myelin sheath formation
Wrapping of axons by oligodendrocyte processes (membranes)
Highly compacted - 70% lipid, 30% protein
82
Microglia
Resident immune cells of CNS
Originate from haematopoietic progenitors which migrate to CNS
Resting- Highly ramified, motile processes
Activated - retract processes, motile
Proliferate at sites of injury (phagocytic)
83
Functions of microglia
Immune surveillance
Phagocytosis (debris)
Synaptic plasticity - pruning of spines
84
Bad microglia
Proinflammatory cytokines which cause microgla to increase inflammation in neuro-degenerative diseases
85
Astrocytes
Star-like cells
Most numerous glial cells in CNS
86
Astrocytes functions
-Structural - define brain micro-architecture
-Envelope synapses
-Metabolic support
-Neurovascular coupling - changes in cerebral
blood flow in response to neural activity
-Proliferation in disease (gliosis or astrocytosis)
87
Define MND
Adult onset neurodegenerative disease characterised by loss of upper (motor cortex) and lower (spinal cord) motor neurones
88
Define MS
Autoimmune demyelinating disease where immune cells attack myelin sheath
89
Tracts of axons that cross midline are called...
commissures
90
Cell bodies located...
In ganglia (dorsal root ganglia)
91
Blood-brain barrier
Dyes injected into blood penetrate most tissues, but not the brain (good for disease prevention in brain but problematic for drug delivery)
Formed by endothelial cell tight junctions (few fenestrations), astrocyte end feet and pericytes
92
Circumventricular organs
Permit hormones to leave brain without interrupting BBB
(e.g - pineal body which secretes melatonin into blood or posterior pituitary which secretes hormones into blood)
93
4 key cell types in gastric epithelium
Chief Cells - produce proteases
Mucous Cells - secrete mucous
Parietal Cells - secrete HCl and intrinsic factor
Enteroendocrine Cells - secrete hormones
94
Gastric Acid Secretion
HCl
Approx 2L per day
Neurohumoral regulation (by vagus nerve and variety of hormones)
95
Pump in gastric parietal cells to decrease lumen pH
Pumps H+ into gastric lumen
Pumps K+ into gastric cell
(K+/H+ ATPase pump)
96
Which 2 ions passively flow out of parietal cell into gastric lumen?
K+ and Cl-
97
Where do H+ ions come from in parietal cells?
Cellular respiration
H2O -> OH- + H+
98
Swapping ions between blood and parietal cells
HCO3- enters blood
Cl- enters parietal cell
99
How are bicarbonate ions produced in parietal cells?
CO2 + H2O (catalysed by carbonic anhydrase) -> H2CO3 -> H+ + HCO3-
100
Turning on gastric acid release (cephalic phase)
Parasympathetic nervous system
Sight, smell, taste, chewing stimulates brain to stimulate stomach via vagus nerve
Done through ACh release: acts directly on parietal cells, but also triggers release of gastrin and histamine (which turn on parietal cells)
101
Turning on gastric acid release (gastric phase)
Gastric distension, presence of peptides / amino acids = gastrin release (acts directly on parietal cells)
Gastrin triggers histamine release (acts directly on parietal cells)
102
Why do proteins in stomach stimulate gastrin release?
Proteins act as buffer mopping up H+ ions (=pH rise) and therefore decreased production of somatostatin
103
Role of somatostatin
Inhibit gastric acid release
104
Turning off gastric acid release (gastric phase)
Low luminal pH = inhibited gastrin secretion indirectly inhibiting histamine release
Stimulates somatostatin release
105
Turning off gastric acid release (intestinal phase)
In duodenum: low pH, hypertonic luminal contents, duodenal distension, presence of fatty acids and amino acids
Triggers release of enterogastrones: secretin and cholecystokinin (CCK)
106
Role of secretin and cholecystokinin (CCK)
Inhibit gastrin release, promote somatostatin release
107
Gastrin, ACh and histamine binding to receptors on parietal cell membranes results in...
Upregulation of H+/K+ ATPase pumps
108
Somatostatin binding to receptors on parietal cell membranes results in...
Dwonregulation of H+/K+ ATPase pumps
109
Autocrine factors
Cells releasing a substance that acts on themselves
110
Paracrine factors
Cells releasing a substance that acts on neighbouring cells (histamine and somatostatin)
111
Hormone
Acts on cells at distant sites
112
Define ulcer
Breach in mucosal surface
113
4 peptic ulcer causes
Heliobacter pylori infection
Drugs (NSAIDS)
Chemical irritants (alcohol, bile salts)
Gastrinoma
114
4 ways gastric mucosa protects itself from ulcers
Alkaline mucus
Tight junctions between cells
Replaces damaged cells
Feedback loops
115
Heliobacter pylori causing peptic ulcers
Lives in gastric mucus
Secretes urease splitting urea into CO2 and ammonia
Ammonia + H+ -> Ammonium (toxic to gastric epithelium) = inflammatory response and reduced mucosal defence
116
NSAIDS causing peptic ulcers
Lessen inflammatory responses by inhibiting cyclo-oxygenase 1 (needed for prostaglandin synthesis and prostaglandins needed for inflammatory response)
Reduce mucosal defence
117
Bile salts causing peptic ulcers
Duodeno-gastric reflex
Regurgitated bile strips away mucus layer
Reduced mucosal defence
118
Proton pump inhibitors which prevent over-secretion of gastric acid
Omeprazole, Lansoprazole, Esomeprazole
119
Role of ranitidine
Prevents histamine from stimulating parietal cell
120
Mucus secreting cells stimulated by...
Prostaglandins
121
Chief cells in gastric mucosa produce...
Pepsinogen (which is a zymogen)
Pepsinogen mediated by input from ENS (ACh secretion like HCl secretion from parietal cells)
122
Pepsinogen activation
In the gastric lumen, pepsinogen and HCl are present (from chief and parietal cells).
HCl cleaves pepsinogen into pepsin
Pepsin can also digest pepsinogen into pepsin (+ve feedback)
Protein -> Peptides
123
Pepsinogen -> Pepsin most efficient at a pH of...
pH less than 2
124
How does the duodenum turn off pepsin production?
HCO3- secreted from Brunner's Glands to increase pH
125
Role of pepsin in protein digestion
Not essential but accounts for ~20% total protein digestion
Breaks down collagen in meat
126
Stomach volume variability
Empty - 50mL
When eating, up to 1.5L with little increase in luminal pressure
127
Receptive relaxation
Relaxation of smooth muscle in body and fundus of stomach to accommodate food
Mediated by Vagus (parasympathetic)
128
Peristalsis in the stomach
Waves of contraction begin in gastric body More powerful contraction in antrum Pylorus closes as contraction reaches it to churn/mix food in stomach
129
What are the pacemaker cells of the GI tract?
Interstitial cells of Cajal which depolarise and repolarise (stronger contraction when stomach is fuller)
About 3 contractions per minute
130
What hormone stimulates increased strength of peristalsis?
Gastrin (due to gastric distension)
131
Strength of peristaltic contractions decreased by...
-Increased duodenal fat
-Increased duodenal osmolarity
-Decreased duodenal pH
-Increased sympathetic NS action
-Decreased parasympathetic NS action
132
Overactive stomach results in...
Dumping syndrome of chyme into duodenum
133
4 saliva functions
-Lubricant for mastication, swallowing and speech
-Oral hygiene (wash, immunity, buffer)
-Digestion
-Remineralisation (Ca(2+) and PO4(3-))
134
Saliva flow rate
0.3-7ml per minute
135
Daily saliva secretion in adults from major and minor glands
800-1500ml
136
Saliva pH range
6.2-7.4
137
2 salivary secretions are...
Serous secretion - a amylase (starch digestion)
Mucus secretion - (mucins for lubrication of mucosal surface)
138
Which gland produces the serous saliva secretion?
Parotid gland
139
Which glands produce both the serous and mucous secretions?
Submandibular and sublingual
140
Minor glands mainly produce what to contribute to saliva?
mucus
141
Factors affecting composition and amount of saliva produced
Flow rate
Circadian rhythm
Type/size of gland
Duration/type of stimulus
Diet
Drugs
Age
Gender
142
What is saliva?
Secretion of proteins and glycoproteins in a buffered electrolyte solution
143
3 defences of oral cavity
Mucosa - physical barrier
Palatine tonsils - provide immune cells
Salivary glands - wash away food/bacteria/viruses
144
Activity of glands in oral cavity
Submandibular, sublingual and minor glands continuously active
Parotid - usually fairly inactive but stimulated by thought of food or chewing
145
What is whole saliva?
salivary gland secretions, blood, oral tissue, microorganisms, food remnants
(can be used for disease diagnosis)
146
2 distinct types of epithelial tissue in salivary glands
Acinar cells (make saliva)
Ducts (carry saliva out of glands into mouth)
147
2 types of acini
Serous acini (water and a amylase)
Mucous acini (water and glycoproteins)
Differences in their appearance
148
Role of myoepithelial cells in a gland
Squeezes the gland pushing saliva out
149
How do cells lining a duct (from a gland) change as they go down the duct?
Change from intercalated to striated duct cells
Striated duct cells allow exchange of ions (like Na+/Cl-/HCO3-) to produce the final saliva product
150
Reason for striations in duct lining cells coming from glands
Striations increase SA to house more mitochondria so more active transport of bicarbonate can occur)
151
Three pairs of major salivary glands contribute what % of total saliva?
Parotid
Submandibular
Sublingual
80%
152
Minor salivary glands contribute what % of total saliva?
What type of acini do they have?
20% (situated all of submucosa of oral mucosa)
All mucous glands except for the serous glands of von Ebner
153
What acini are found in the parotid gland?
Serous acini
154
What acini are found in the submandibular gland?
Mix of serous and mucous acini (referred to as seromucous)
155
What acini are found in the sublingual gland?
Mix of serous and mucous acini (but more mucous acini)
156
Stenson's duct
Major duct that connects parotid gland to oral cavity
157
Which nerve runs very close to parotid gland?
Facial Nerve
158
Where do submandibular glands lie?
Under tongue
159
2 lobes of submandibular glands?
What separates them?
Larger superficial lobe
Smaller deep lobe in floor of mouth
Separated by mylohyoid muscle
160
Wharton's duct
Major submandibular duct begins in superior lobe wrapping around posterior border of mylohyoid
Runs along floor of mouth emptying into oral cavity at sublingual papillae
161
Location of sublingual glands
Between mylohyoid muscle and oral mucosa of floor of mouth
162
If salivary output falls below 50% of normal flow...
Patient experiences xerostomia (dry mouth)
163
Glucose pathway from consumption
Absorbed in intestine taken to liver in bloodstream
Distributed to muscle, brain, RBC, adipocytes (storage)
164
Conversion of glucose to glycogen storage in the liver is stimulated by...
Insulin
165
What happens to excess glucose in the liver?
Converted into Acetyl Co-A and either fed into Kreb's or makes triglycerides -> very low density lipoproteins
166
2 stores of glycogen
Liver and skeletal muscle cells
167
What happens to glucose sent to brain?
Converted to Acetyl CoA which enters Kreb's and forms ATP
168
What happens to glucose sent to RBCs?
Converted to pyruvate (then lactate)
169
What happens to glucose sent to adipocytes?
Converted to triglycerides (stimulated by insulin)
170
Triglycerides are insoluble in water so are carried around the body bound to a protein forming a...
Chylomicron or a VLDL
171
What do chylomicrons travel in back to blood system?
Lymphatic system
172
What promotes glycogen in liver to be broken down into glucose?
Glucagon (by glycogenolysis)
173
Where does energy come from when glycogen stores are used up?
-RBCs release lactate to be used as energy
-Amino acids released from muscle breakdown
-Triglycerides in adipocytes broken down into glycerol
(All sent to liver for gluconeogenesis)
174
During fasting, triglycerides in adipocytes are broken down into...
Glycerol (converted to glucose in liver) and fatty acids (used instead of glucose or converted to ketones in the liver)
This process is lipolysis
175
Which hormone stimulates breakdown of triglycerides? in lipolysis?
Glucagon
176
After prolonged fasting, gluconeogenesis decreases leading to an increase in...
Ketoneogenesis - ketones are used by the brain for energy instead of glucose so therefore there is enough glucose available to be used by RBCs
177
3 hormones released from the adrenal gland?
Adrenaline
Noradrenaline
Cortisol
178
2 hormones released form the pancreas?
Insulin
Glucagon
179
Hormone released from thyroid gland? What is the hormone's role?
Thyroxine - speeds up metabolism
180
2 hormones released from pituitary gland?
Growth hormone
Somatostatin
181
Insulin vs Glucagon?
Insulin promotes glycogen and fat storage and protein synthesis (anabolic)
Glucagon promotes glycogenolysis, gluconeogenesis, ketogenesis (catabolic)
182
3 things that use up energy?
Activity
BMR
DIT
183
Leptin action in controlling appetite
Normal weight - suppresses appetite
In obesity - High leptin levels = leptin resistance = appetite not suppressed
184
Ghrelin role in controlling appetite
"Hunger Hormone"
Increases before meals
Stimulates appetite
185
Xenobiotics
Foreign substances of no nutritional value (can be harmful if not excreted)
Come form food/drink/breathing
186
Group of enzymes called ..... play major role in process of detoxification
Cytochrome P450 enzymes (specifically in phase 1)
187
Xenobiotic biotransformation reaction split into 2 phases...
Phase 1 (non-synthetic) - Addition/exposure of small functional groups (amine, hydroxyl etc.) (small increase in hydrophilicity)
Phase 2 (biosynthetic) - Addition of endogenous molecules (large increase in hydrophilicity)
188
Purpose of xenobiotic biotransformation
Make compounds less toxic and water soluble so can be excreted
189
Where does detoxification occur?
Mostly in liver but also in lungs and small intestine
190
Common features of cytochrome P450 enzymes
Present in SER
Oxidise the substrate and reduce oxygen
They're inducible enzymes
They generate a free radical compound
191
2 exocrine secretions of pancreas
Aq bicarbonate
Enzyme
192
2 transport routes of epithelial cells in GI tract
Paracellular pathway
Transcellular pathway
193
Pancreas endocrine function
Secretes insulin and glucagon from islets of Langerhans
194
Pancreas exocrine function
Secretion of pancreatic juice
195
Ethanol metabolism
Only 2-10% excreted as it's used as a fuel
Used to produce NADH (using alcohol dehydrogenase (ADH))
196
Cycle of principal blood flow through liver
Heart -> Abdominal Aorta -> Proper Hepatic Artery -> Liver -> Hepatic Veins -> IVC -> Heart
197
Liver microanatomy
Organised in lobules with a central (hepatic vein) surrounded by a hexagon of 6 portal triads
198
What constitutes a portal triad
Portal Vein
Hepatic Artery
Bile Ducts
199
8 Liver Roles
Detoxification - cleans bloods of waste products
Immune Function
Synthesis - clotting factors, glycogen, enzymes
Bile Production
Bilirubin breakdown
Energy storage (glycogen, fats)
Regulating fat metabolism
Ability to regenerate
200
Liver is regulated by 2 things...
Endocrine glands (pancreas, adrenal, thyroid)
Nerves
201
Define lipid
Esters of fatty acids and glycerol or other compounds (cholesterol)
202
What is the storage form of fat in our body?
Triglycerides in adipocytes, hepatocytes, etc.
203
Saturated fatty acids are...
Unsaturated fatty acids are...
Solid
Liquid
204
Liver vascular supply
Afferent:
75% portal vein
25% hepatic artery
Efferent:
Hepatic veins
205
3 Lipid functions
Energy Reserve
Structural (part of cell membranes)
Hormone metabolism
206
Lipids yield how much energy per gram?
9-10 kcal
207
How are lipids often transported in blood?
As triglycerides
As fatty acids bound to albumin
208
How do lipids enter a cell?
TGs can't diffuse through membrane so FAs are released by lipases to facilitate transport (via several transporter systems like FA binding protein) into cells
In cell, FAs are re-esterified into TGs
209
Breakdown of triglycerides at adipocytes catalysed by...
Hormone Sensitive Lipase
210
Breakdown of triglycerides in blood catalysed by...
Lipoprotein Lipase
211
Breakdown of triglycerides in hepatocytes catalysed by...
Hepatic Lipase
212
Insulin action in fat metabolism
Fat storage in adipocytes
Stimulates LPL to breakdown TGs releasing FFAs which can be stored in the form TG in the adipocyte
Reduces activity of HSL reducing FA export from adipocytes
213
Insulin resistance in fat metabolism
Increased lipolysis in adipocytes = increased TG in circulation
Increased offer of FA to hepatocytes = greater uptake = increased glucose level and less demand of lipids to be used
214
What constitutes a lipoprotein?
A core containing TGs and cholesterol-esters and a surface monolayer of phospholipids, cholesterol and specific protein
215
How are lipoproteins defined?
By their density (LDL, HDL, chylomicron)
216
Chylomicrons role
Carry lipids from gut to muscle and adipose tissue
217
Chylomicrons fate
The remnants taken up by receptor mediated endocytosis
218
How is cholesterol esterified intracellularly?
acyl-CoA:cholesterol acyltransferase
219
How is cholesterol esterified in lipoproteins?
By lecithin:cholesterol acyltransferase
220
What % of cholesterol is endogenous?
90%
221
What is the major organ in which cholesterol is processed?
Liver
222
Only method of cholesterol export
Through bile (it's a constituent of bile)
223
What is De novo lipogenesis?
Converts excess dietary starch, sugar, protein, and alcohol into specific fatty acids
224
Rate limiting step of De novo lipogenesis
Acetyl-CoA to Malonyl-CoA catalysed by Acetyl-CoA carboxylase
225
Fatty acid export from liver
ApoB 100 synthesised in RER
Lipid components (TG, cholesteorlester) synthesise in SER
These are added by TAG transfer protein to ApoB
Transported to GA where ApoB is gylcosylated
Glycosylated Apo-s with lipid componetns bud off GA and migrate to sinusoidal membrane of hepatocyte
Vesicles fuse with membranes and VLDL released
226
Fatty acid oxidation occurs at 3 locations in the liver... (to produce acetyl co-A)
Mitochondrial beta oxidation
Peroxisomal beta oxidation
ER Microsomal omega oxidation
227
Peroxisomal b oxidation
Normal ribosomal function
228
Mitochondrial beta oxidation
Progressive shortening into acetyl-CoA subunits (condensed into ketone bodies which enter TCA cycle)
229
ER Microsomal omega oxidation
CYP4A enzymes oxidise saturated and unsaturated fatty acids
omega-hydroxylation in the ER
Then, decarboxylation of the omega-hydroxy FA in cytosol
This product then enters b-oxidation pathway
230
Main source and loss of nitrogen
Source - Dietary protein
Loss - gut and kidneys as urea
231
Amino acid structure
H
H2N-------C-------COOH
R
232
Link between 2 amino acids
Dipeptide
Peptide bond (C-N)
233
How many amino acids in a polypeptide vs a protein
Polypeptide = <50
Protein = >50
234
Nitrogen said to be in balance if...
N intake (from dietary protein) is roughly equal to N excretion (+/- 4g/day)
235
Recommended daily dietary protein intake
0.75g/kg/day
236
3 sources of N loss
Renal excretion (70g/day)
Faecal loss (10g/day)
Skin/hair/sweat loss
237
Essential vs non-essential amino acids
Amino acids said to be essential if they can't be synthesised de novo in vivo
Some amino acids are conditionally essential (so only essential under certain circumstances)
238
Which non-protein molecules are synthesised used N from dietary protein?
Neurotransmitters, nitric oxide, nucleotides
239
3 roles of albumin
Maintaining appropriate osmotic pressure
Binding and transport of hormones, drugs, etc
Neutralisation of free radicals
240
Transamination of alanine
Alanine + a-ketoglutarate <--> Pyruvate + Glutamate
(catalysed by ALT)
241
242
Cortisol role in AA catabolism
+ proteolysis
- protein synthesis
+ gluconeogenesis
243
Glucagon role in AA catabolism
+ glycogenolysis
+ gluconeogenesis
+ AA degradation
+ ureagenesis
+ entry of AAs to liver
244
What is bile?
Lipid rich solution containing water, inorganic electrolytes and organic solvents (bile acids, phospholipids, cholesterol, bile pigments)
245
Bile secretion per day from gall bladder
500-600ml per day
246
What circulation means the liver doesn't have to synthesise as much bile?
Enterohepatic circulation - Most bile acids secreted by hepatocyte have been previously secreted into intestine
247
3 bile functions
Fat digestion/absorption
Cholesterol homeostasis
Excretion of lipid soluble xenobiotics
248
Bile acids (major constituent of bile) are synthesised from... in ...
Synthesised from cholesterol in hepatocytes
249
What are the primary bile acids formed from cholesterol (lipid soluble)?
Cholic Acid (CA)
Chenodeoxycholic Acid (CDCA)
(water soluble)
250
What happens to bile acids before being secreting into bile?
(mechanism to trap them in the lumen of the intestine)
CA and CDCA are conjugated making them more hydrophilic and more acidic which makes them stay in the lumen of the intestine
251
Bile acids are amphipathic meaning...
Likes water and fat which aids emulsification of lipids (increasing SA) into the aq solution of the lumen
252
Process of digesting fat within a fat globule
Amphipathic bile salts and phospholipids surround a TG
Amphipathic protein (colipase) allows lipase to get into close approximation to the emulsion droplet and digest the TG
253
How do FAs and MGs enter the enterocytes?
Fatty acids and monoglycerides associate with phospholipids and bile acids allowing aq diffusion through channels into enterocyte (as the bile acids are amphipathic)
254
What happens to FAs and MGs once they are absorbed into the enterocyte?
They reform triglycerides and are exocytosed into the blood stream as chylomicrons
255
What happens to FAs and MGs once they are absorbed into the enterocyte?
They reform triglycerides and are exocytosed into the blood stream as chylomicrons
256
Fate of bile in fasted vs fed state (enterohepatic circulation part 1)
Fasted - bile acids travel down biliary tract from liver -> gallbladder (where they're concentrated 10x)
Fed - CCK released from duodenal mucosa which relaxes Sphincter of Oddi and contracts gallbladder releasing concentrated solution of mixed micelles (BA, PL, cholesterol)
257
Bile acid reabsorption (enterohepatic circulation part 2)
Bile acids conjugated (so remain intraluminal)
Actively transported via apical sodium bile acid transporter (ASBT) into terminal ileum
Re-enters liver via portal circulation
Bile acids taken up by hepatocyte and secreted back towards gall bladder
258
How many enterohepatic cycles per meal
2-3 cycles
259
Bile acid negative feedback mechanism in terminal ileum
Bile acid binds to Farnesoid X Receptor in terminal ileum triggering synthesis of FGF 19 (hormone)
FGF 19 then inhibits CYP7A1 reducing bile acid production
260
Role of CYP7A1
Stimulates conversion of cholesterol into primary bile acids (CA and CDCA) in the liver
261
Na absorption in intestine
Glucose/Na (SGLT1) co-transporter on apical membrane brings Na into enterocyte
Na+/K+ATPase transporter then moves 1 Na cell->blood and 1 K blood->cell (on basolateral membrane)
262
Glucose absorption in intestine
Glucose/Na (SGLT1) co-transporter on apical membrane brings Glucose into enterocyte
GLUT2 transporter then takes glucose from cell->blood (on basolateral membrane)
263
cAMP effect on intestinal secretion
Works to shift Cl- from body into gut lumen
264
4 factors affecting intestinal absorption
Number and structure of enterocytes
Blood and lymph flows
Nutrient intake
GI motility
265
What breaks down maltose, sucrose and lactose (disaccharides) into monosaccharides?
Maltase, sucrase, lactase
266
Enterocytes absorb glucose and galactose by the Na co-transporter but absorb fructose by...
Facilitated transport
267
4 saliva functions
Lubricates, cleans oral cavity
Dissolves chemicals
Suppresses bacterial growth
Digest starch by amylase
268
Secretions of the mucous neck cell (in the stomach)
Mucus
Bicarbonate
269
Secretions of the parietal cells (in the stomach)
Gastric acid (HCl)
Intrinsic factor (complexes with Vit B12 to permit absorption)
270
Secretions of Enterochromaffin-like cells (in the stomach)
Histamine
271
Secretions of chief cells (in the stomach)
Pepsin(ogen)
Gastric lipase
272
Secretions of D cells (in the stomach)
Somatostatin (inhibits gastric acid secretion)
273
Secretions of G cells (in the stomach)
Gastrin
274
A lot of gastric acid secretion stimulated by...
Parasympathetic pathway of vagus nerve
275
Acidosis vs Acidemia
Acidosis - Disorder tending to make blood more acidic than normal
Acidemia - Low blood pH
276
Alkalosis vs Alkalemia
Alkalosis - Disorder tending to make blood more alkaline than normal
Alkalemia - High blood pH
277
Transamination reaction between pyruvate and glutamate at the muscle (glucose-alanine cycle)
Alanine aminotransferase (ALT) removes the amino group from glutamate forming alpha-ketoglutarate and adds it to pyruvate forming alanine (opposite occurs at liver)
278
Link between Kreb's and urea cycle
Fumarate produced in urea cycle can be fed into Kreb's
Aspartate produced in Kreb's can be fed into urea cycle
279
Where does the urea cycle take place?
Mitochondria and cytosol
