Hepatobiliary and GI Function Flashcards
Progression steps of digestion
Mouth to anus
- Mouth: taste, chewing, bolus formation
- Esophagus: transport
- Stomach: Storage, grinding, mixing, digestion, acid secretion
- Small intestine: digestion, absorption
- Large intestine: fluid and electrolyte absorption
- Rectum: Storage and excretion
Accessory organs to digestions
Pancreas: Digestions and HCO3- buffer
Liver: Metabolism, detoxification, bile formation
Gallbladder: Bile Storage
Pancreas buffers stomach acid / Bile helps digest lipids
Transit time of food to excretion
- Esophagus transit time: 10 s
- Time to small intestine: 1-3 h
- Time to ileocecal valve: 7-9 h
- Time to decending colon: 25-30 h
- Excretion: 30 h
what are the 5 functions of the liver?
carb metabolism
synthesis of plasma proteins
synthesis of lipoproteins
immunity
inactivation of toxins
what is the liver triad?
- hepatic artery
- portal vein
- bile duct
what does the liver do for immunity?
kupffer cells produce lymph
liver blood supply
25% from celiac artery
75% from portal vein (drains from GI system)
how much blood pools in the liver
10%, 500mL
how much nutrients does the liver take (first pass)
1/3-1/2 of nutrients
not fat or suppositories
How to avoid first pass effect?
Different ways to administer drugs?
Topical
Inhaled
Sublingal
Injectable
Liver metabolism: Lipids
- Fatty acid oxidation: Acetyl-CoA
- Ketone formation: (Keto acidosis)
- Synthesize lipoproteins, cholesterol, phospolipids
Liver metabolism: Carbs
- Glucogenesis (Amino Acids)
- Glycogensis (glycogenolysis)
- Hormonal control of glucose release
Liver metabolism: Proteins
- Synthesizes plasma proteins
- Cirrhosis decreases albumin and clotting factors
- Increase of unbound fraction of drugs (larger impact systemically)
- Urea
Liver metabolism on anesthesia
Surgery is stressful. Relases of catecholamines, glucagon, and cortosol. Results in mobilization of carb and protein storage causing hyperglycemia and negative nitrogen balance
Iso and Sevo increase blood glucose levels, Propofol does not (lipid based)
Liver and Urea Recycling
- Deamination = Ammonia (NH3) [85% enters via portal circulation]
- Uptake and Ureagenesis
- GFR (75% of systemic flow after exit from liver)
- GI (25% of systemic flow after exit from liver) Ammonia and Ammonium Ion (NH4)
Liver detox
What toxins? MIDCAP-MF
Metabolic end products
Insecticides
Drugs
Contaminants / Pollutants
Alcohol
Pesticides
Mico-organisms
Food additives
*fat-soluble
Liver Detox: Phase 1
P450’s
Liver Detox: Phase 2
conjugation
ionize, to make water soluble
Liver Detox: Waste Products
Two paths of elimination
- Gallbladder→Bile→Stool
- Kidneys→Urine
Bilirubin production and excretion
- Hemoglobin degraded to bilirubin by the reticuloendothelial system
- Bilirubin is carried in circulation by albumin (bound to it)
- Hits liver: bilirubin is conjugated with glucuronic acid by UDP glucuronyl transferase
- Part of the conjugated bilirubin (glucuronide and bilirubin sulfate) is H2O soluble and excreted into bile
- In the intestine conjugated bilirubin is converted to urobilinogen
- 18% returned to the liver via the enterohepatic circulation then excreted in urine as urobilin (2%)
- 80% is excreted in feces as urobilin and stercobilin
Obstructive / Conjugated / Direct
Bulirubin in Plasma? Yes
Bilirubin in Urine: Yes
Hepatobiliary dx (Cholestasis)
obstruction of the bile ducts, can not be released into the digestive tract
Hemolytic / Unconjugated / indirect
Bilirubin in plasma? Yes
Bilirubin in Urine? No
Impaired conjuction or overproduction
Albumin and bilirubin
Unconjgated bilirubin tighhtly binds to albumin creating an excess in the system
Conjugated bilirubin does not bind as tightly therefore can be excreted in the urine
Markers of liver inflammation / injury
- Asparate transaminase (AST)
- Alanine transaminse (ALT)
- Alkaline Phosphatase (AP)
Markers of liver function
- Total bilirubin
- Albumin
Most liver disease lab values
ALT > AST
Alcholic liver disease lab values
AST > ALT
Gallbladder disease lab values
AP +/- TB
Cirrhosis / Ascites loop
Cirrhosis causes:
* Lowered albumin which lowers colloid oncotic pressure (pushes fluid out)
* Increased liver sinusoids resistance which increases portal pressure
* This causes fluid loss and decreased venous return
* This increases RAAS and ADH to compensate for hypovolemia
* Increases BP which pushes out more fluid…cycle continues
Bam ascites
what are the three things that control GI blood supply
arteriole control (vasodilators)
ANS command (PNS and CNS)
local events
local events, metabolic and myogenic mechanisms
what are the vasodilators for the GI arterioles?
NO
VIP
Ach
Substance P
when you are in shock what does that do to your absorption
ischemic villus (impaired)
what are the two local events that can change blood supply?
metabolic (changes in oxygen)
myogenic (stretch/tension)
Three control machanisms of GI function
- Hormonal regulation
- Neurogenic Innervation
- Myogenic pacing
Hormonal regulation of GI tract
- Endocrine
- Paracrine (can effect neighbor cells, chain reaction)
- Exocrine
Neurgenic Innervation of the GI tract
- Extrinsic (Autonomic NS)
- Intrinstic (Enteric NS)
Myogenic pacing of the GI tract
Autonomous smooth muscle contractions
- Pacemaker activity
- electrical coupling
GI Hormone: Gastrin
Source
* G Cells (antrum stomach, duodenum)
Stimulation:
* Peptides / Amino Acids
* Distention of stomach
* Vagal Stimulation (GRP)
Action
* Increased gastric acid (H+)
* Increased growth of gastric mucosa (to protect stomach lining)
* Increased gastric motility (emptying)
GRP = Gastrin releasing peptide
GI Hormone: CCK
CCK: Cholecystokynin
Source:
* I Cells (duodenum and jejunum)
Stimulation:
* Peptides / Amino Acids
* Free Fatty Acids
Action:
* Increased gallbaldder contraction / relaxation of sphicter of Oddi
* Increased pancreatic enzyme / HCO3- sectretion (weaker than secretin)
* Increased trophic effects on pancreas and galbladder
* Decreased gastric emptying
GI Hormone: Secretin
“Natures antacid”
Source:
* S Cells (duodenum and jejunum)
Stimulation:
* H+ (pH under 4.5)
* Free Fatty Acids
Action:
* Increased pancreatic and biliary HCO3- secretion
* Increased trophic effects on pancreas
* Decreased gastic acid (H+)
* Decreased growth of gastic mucosa
GI Hormone: GIP (GLIP) / GLP
Source:
* GIP = K Cells (duodenum and jejunum)
* GLP = L Cells (duodenum and jejunum)
Stimulation:
* Oral glucose
* Peptides / Amino Acids
* Free Fatty Acids
Actions
* Increased pancreatic insulin secretion
* Decreased gastic acid (H+)
GI Hormone: Motilin
Source:
* M-Cells (duodenum and jejunum)
Stimulation:
* Neural
* Decreased vagus signaling (fasting)
Action:
* Increased migrating motor complex during fasting to clear excess debris from GI system
* Helps prevent small intestinal bacterial overgrowth (SIBO)
GI Hormone: Somatostatin
Source:
* Delta Cells (D Cells) from pancreatic islets and GI mucosa
Stimulation:
* Acid (H+)
Action:
* Decrease release of GI hormones (Gastrin, CCK, Secretin, GIP etc)
* Decreased gastric acid (H+)
* Decreased pacncreatic enzyme / HCO3- release
* Decreased gallbladder contractions
Off switch for GI tract, fight or flight mode
GI Neurotransmitter: NE
Sympathetic innervation
* Decreased motility
* Decreased secretions
* Increased constriction of sphincters
* Vasoconstriction
GI Neurotransmitter: ACh
Parasympathetic / Enteric
* Increased motility
* Increased secretions
* Decreased constriction of sphincters
* Vasodilation
GI Neurotransmitter: VIP
Enteric
* Increased smooth muscle relaxation
GI Neurotransmitter: GRP
Enteric
* Increased gastrin secretion
An increase in sympathetic activity does what?
GI Tract
Slows digestion and absoption
An increase in parasympathetic activity does what?
Gi Tract
Promotes digestion and absoption
What are ICC cells
- Interstital Cells of Cajal
- Pacemaker cells of the gut
- Partially innervated by Enteric NS but not a part of it
Myogenic pacing via BER
Basal Electrical Rhythm aka slow waves
Always there at a slow pace and low rate
On graph depole is spikes
More spikes = more contractions
does sympathetic or parasympathetic make saliva more protein rich?
sympathetic
Which system produces more saliva? Symp or Parasymp?
Parasympathetic
Saliva formation
- Interstitial fluid (isotonic) flows into acinar cells
- While it flows along ductal cells electrolytes flow in and out
- In: K+ and HCO3- (concentration verse plasma? increased)
- Out: NA+ and Cl- (concentration verse plasma? decreased)
- Saliva is secreted (hypotonic)
what 3 things stimulate gastric acid (HCl) release?
ECL Cells (Histamine): Strongest
ACh (Vagus): Strong
G cells (Gastrin): Weakest
What two things inhibit gastric acid?
- Somatostatin
- Prostaglandins
What recepors are used for gastric acid release?
- Vagus→ACh→M3
- G cells→Gastrin→CCK-B
- ECL Cells→Histamine→H2
All three work together to secret gastric acid. How?
ACh / Histamine / Gastrin
Vagal - ACh
* Release is stimulated by sight and smell
* Reflexivity to stomach stretch (vago-vagal)
* Parietal Cell + ACh = HCl
* ECL Cell + ACh = Histamine → Parietal Cell + Histamine = HCl
ECL Cell - Histamine
* Stimulated by ACh and Gastrin
* Parietal Cell + Histamine = HCl
G Cell - Gastrin
* Stimulated from ENS by GRP
* ECL Cell + Gastrin = H+ release = HCl
* Parietal cell + Gastrin = HCL
What is the most important stimulant for pancreatic enzyme secretion?
CCK
The effects of secretin are potentiated by what?
Two
- CCK
- ACh
Pancreatic secretions are what?
- More alkaline than saliva (pH 8.6)
- Isotonic to plasma
Food is isotonic at this point; hypotonic secretions are not needed
Pancreatic enzyme: Amylase
Secreted as:
* Active enzyme
Function:
* Starch digestion
Pancreatic enzyme:
* Trypsinogen
* Chymotrypsinogen
* Procarboxypeptidase
* Proelastase
Secreted as:
* Proenzymes
Activation:
* Enteropeptidase to trypsin
* Proelastase activated by trypsin
Function:
* Protein digestion
Pancreatic enzyme:
* Lipase
* Cholesterol esterase
* Phospholipase
Secreted as:
* Active enzyme
Function:
* Fat digestion
* Cholesterol esters
* Phospholipids
Pancreatic enzyme:
* Deoxyribonuclease
* Ribonuclease
Secreted as:
* Active enzyme
Function:
* Nucleic acid digestion
Circulation of bile
- Hepatocytes (formation)
- Gallbladder (storage and concentration)
- Release into system (CBD into duodenum)
- Reabsorption (95% by ASBT in gut)
- Return to liver via portal vein
ASBT
Active absoption:
Apical sodium-dependent bile salt transporter
what 2 things cause bile to go into gallbladder?
hepatic secretion pressure
pressure from closure of oddi
how is the bile concentrated?
Cl- and bicarb are pumped out with water
what is the ideal bile ratio?
bile salts: lecithin: cholesterol
10:3:1
How do we get gall stones?
Too much cholesterol
Too little bile salts
Too little lecithin
GI secretions: Saliva
Major characteristics:
* High HCO3-
* High K+
* Hypotonic
* Amylase
* Lingual lipase
Stimulated by:
* Parasympathetic
* Sympathetic
Inhibited by:
* Sleep
* Dehydration
* Atropine
GI secretions: Gastric
Major characteristics:
* HCl
* Pepsinogen
* Intrinsic factor
Stimulated by:
* Gastrin
* Histamine
* Parasympathetic
Inhibited by:
* low stomach pH
* chyme in duodenum
* somatostatin
GI secretions: pancreas
Major characteristics:
* Secretin
* CCK
* parasympathetic
GI secretions: Bile
Major chaacteristics:
* Bile salts
* Bilirubin
* Phospholipids
* Cholesterol
Stimulated by:
* CCK (GB contraction / Oddi relaxation)
* parasymapathetic (GB contraction)
Inhibited by:
* Ileal resection
peristalsis? where does this occur?
- propulsion through the area
- esophagus
- stomach
- Small intestine
- large intestine
segmentation? where does this occur?
- used for mixing
- stomach
- small intestine
- large intestine
tonic contraction? where does this occur?
just a held contraction of sphincters
How is swallowing controlled?
- Medulla (swallowing center)
- Upper Esophageal Sphincter (Skeletal muscle)
- Esophagus (first 3rd striated, last 2/3 smooth)
- Lower esophageal sphincter (smooth muscle)
Swallows are blank , the response of peristalsis is blank?
- voluntary
- reflexive
Antiperistalsis?
Opposite direction of peristalsis
can being as low as ilium
prelude to vomiting
pushes GI contents into duodenum
distentions excite vomiting act
Vomiting act
- Deep breath
- UES opens
- Glottis closes
- Elevation of soft palate
- Diaphram contraction + abdominal muscles contract
- LES relaxes
- Expulsion of contents
CTZ
Chemoreceptive Trigger Zone
- postrema of medulla
- Dopamin and Saratonin receptors
what does a vagotomy impair in the stomach
relaxation of the stomach (cant eat as much)
roux en Y gastric bypass
gold standard for weight loss surgery
60% weight gone
correct T2D
what are the 6 probelms with RYGB surgery?
1 faster food motility so less dig/abs
2 dumping diarrhea
3 intake less water because feel full constantly
4 decrease glucose absorption
5 vitamin B12 deficiency
6 mineral (iron and calcium) deficiency
