Exam 6 Flashcards
Tell me three general input methods that regulate the GI system
endocrine, paracrine (autocrine), neurocrine
What are the 3 divisions of the ANS? Describe the one that has the most direct effect on the regulation of the GI system
SNS, PNS, enteric nervous system
enteric: located entirely in the GI tract, regulated by both local stimuli and those from the PNS and SNS but can function completely independently of the CNS
Name the 4 general types of intrinsic (ENS) neurons that innervate the GI system
motor neurons, sensory neurons, associative neurons (interneurons), intestinofugal neurons
Tell me the 4 main functions of the intrinsic motor neurons of the enteric nervous system
- stimulate and inhibit smooth muscle contraction
- promote vasodilation
- regulate electrolyte and water secretion
- regulate secretion of hormones, electrolytes, water, etc.
Tell me the 3 main types of sensory neurons intrinsic to the enteric nervous system
nociceptive, mechanoreceptive, chemoreceptive
Tell me the function of the intestinofugal neurons intrinsic to the enteric nervous system
regulate sympathetic ganglia
Name the 3 general types of extrinsic neurons that affect the GI tract’s activity
sympathetic, parasympathetic, sensory neurons
Tell me the 3 kinds of extrinsic sympathetic neurons that innervate the GI tract
motility inhibiting neurons, vasoconstrictor neurons, secretomotor inhibiting neurons
Tell me the 5 main neurons/pathways the parasympathetic system uses to extrinsically innervate the GI tract
- motility stimulating
- vasodilatory neurons
- secretomotor stimulating neurons
- ENS inhibitory pathways
- ENS excitatory pathways
Tell me the 3 main kinds of sensory neurons that provide extrinsic innervation to the GI tract
nociceptive, mechanoreceptive, chemoreceptive
Do the SNS and PNS regulate GI function indirectly or directly?
both! some neurons synapse directly with ENS cell bodies and others meet with a preganglionic neuron first
Tell me the major neurotransmitter of the PNS that regulates activity of the GI tract, as well as what kind of NT it is and what its 3 major functions are there
Ach! Excitatory!
vasodilation, increases secretions, smooth muscle contraction
*may be mediated indirectly through ENS
Tell me the major neurotransmitter(s) of the SNS that regulate activity of the GI tract and tell me what kind of NT the main one is, as well as 3 of its major functions there
Norepinephrine! Inhibitory!
(also Epinephrine and dopamine)
vasoconstriction, inhibits smooth muscle contraction, decreases secretions
Tell me the 5 main neurotransmitters of the ENS
Ach, serotonin, dopamine, nitric oxide, Vasoactive intestinal peptide (VIP)
Tell me what type of NT acetylcholine is, as well as what its 3 main functions are in the ENS
excitatory
induces vasodilation, increases smooth muscle contraction, stimulates secretions
Tell me what type of NT serotonin is, as well as what its 3 main functions are in the ENS
excitatory
induces vasodilation, increases smooth muscle contraction, stimulates secretions (interneurons)
Tell me what type of NT dopamine is, as well as what its 2 main functions are in the ENS
inhibitory
inhibit ENS neuronal firing, decreases amount of NT released
**typically works as a presynpatic regulator
What two NT are typically released together in the ENS?
NO and VIP!
Tell me what type of NT nitric oxide is, as well as what its major function is in the ENS
inhibitory
smooth muscle relaxation (vascular and GI)
Tell me what type of NT vasoactive intestinal peptide (VIP) is and what its main function is in the ENS
inhibitory
smooth muscle relaxation
vascular and GI
Tell me the 3 primary regulators of the GI smooth muscle and what their function is
- Ach (stimulates contraction)
- VIP (inhibits contraction)
- NO (inhibits contraction)
Tell me the 4 types of GI motor activity
- segmental contractions (mixing)
- peristaltic contractions (moving)
- reverse peristaltic contractions (storing and keeping empty)
- migrating motor complex (MMC)
Describe the state of smooth muscle cells in the GI tract at rest
smooth muscle cells are electrically active (waves of depolarization and repolarization = resting slow wave, BER [basal electrical rhythm]) – if a stimulus is applied, at the peak of that wave (the depolarized section) there will be a spike potential (rapid depolarization) that will induce an actual contraction
The more spike potentials at the peak of that wave, the greater the contraction
Name the 2 major types of contractions related to GI motility
segmental vs. persistaltic
GI is also regulated in part by striated muscle - name the 3 structures that do this
- upper esophageal sphincter
- upper 1/3 of esophagus
- external anal sphincter
What are sphincters and what are their purposes in the GI tract?
specialized circulate muscles that regulate anterograde and retrograde movements of food
How many total sphincters are there in the GI tract? Name them!
there are six!
- upper esophageal sphincter (UES)
- lower esophageal sphincter (LES)
- pyloric sphincter (PS)
- ileocecal sphincter (IS)
- internal anal sphincter (IAS)
- external anal sphincter (EAS)
upper esophageal sphincter
- separates pharynx and upper esophagus
- striated muscle
- closed during inspiration
lower esophageal sphincter
- separates esophagus and stomach
- permits movement of food into the stomach
- prevents reflux of stomach contents into the esophagus
pyloric sphincter
- separates stomach and duodenum
- regulates gastric emptying
ileocecal sphincter
- separates ileum and cecum
- ileum distension relaxes the sphincter
- ascending colon distension causes contraction of the sphincter
internal anal sphincter
- involuntary control
- distension of rectum relaxes sphincter
external anal sphincter
- striated muscle under voluntary and involuntary control
- if defecation is not desired, involuntary reflex contracts EAS
- if defecation is desired, voluntary and involuntary relaxation of EAS
- voluntary contraction of EAS can override defecation reflex
In general terms, what provides blood supply to the GI tract?
liver’s venous portal system
What 8 major factors increase blood flow in the GI Tract?
- 8 fold increase in blood flow following a meal = postprandial hyperemia
- sequential dilation along GI tract (first stomach, then more distal tissues)
- flow is regulated primarily to muscularis layers and through the villi and submucosa
- vasodilation is maintained for 2-4 hours following a meal
- PNS
- NT like VIP
- low oxygen
- hyperosmolarity
What major factors decrease blood flow in the GI tract?
SNS innervation of vascular smooth muscle:
- NT norepinephrine
- alpha adrenergic receptors
List the 6 major functions of saliva
- prevent dehydration of oral mucosa
- lubrication for mastication and swallowing
- oral hygiene
- digestion
- smell, taste
- neutralize gastric acid that refluxes back into the esophagus
Describe the 2 different types of saliva
- serous (watery): contains salivary enzymes such as alpha amylase
- mucus: contains water, electrolytes, phospholipids, and mucin
What is mucin? Where can we find it?
a highly glycosylated protein with multiple functions; found in mucus type saliva
What is the primary NT stimulus for secreting water for saliva formation?
Ach
Describe the process of water secretion for saliva formation
- isotonic fluid becomes progressively more hypotonic
- Na reabsorption is greater than K secretion
- rate of secretion effects tonicity
- normal pH 6-7; during active secretion it becomes about 8
As water is secreted to form saliva, what else do we secrete to help neutralize the solution?
bicarb!
What NT is the primary stimulus for secreting the proteins/enzymes used in saliva formation?
Ach
List the 10 key salivary secretions and their functions
- alpha amylase - starch digestion
2, 3, 4. immunoglobulin A (IgA), lysozyme, lactoferrin - antimicrobial - lingual lipase (acid resistant) - fat digestion
- mucin - lubrication, protection
- water - taste, swallowing, speech
8-10. Na, K, Cl, HCO3, H20 - alkalization and HCO3 neutralize gastric acid
In order to swallow, what two kinds of muscle do we use? Describe the outflow methods (2) that make these muscles work
striated and smooth!
- somatic nerves regulate striated muscle directly
- autonomic nerves regulate smooth muscle via enteric nervous system or directly
Describe esophageal motor activity in general terms - is it voluntary or involuntary?
initiated voluntarily, followed by reflex control, and respiration is inhibited to prevent food from entering trachea
Name the 3 phases of esophageal motor activity
- oral phase
- pharyngeal phase
- esophageal phase
Describe the oral phase of esophageal motor activity (4)
- voluntary phase
1. tip of tongue separates a bolus of food by pressing against hard palate
2. bolus moves into the pharynx where the food stimulates touch receptors
3. swallowing reflex is initiated
Describe the pharyngeal phase of esophageal motor activity (6)
- soft palate is pulled to prevent reflux into the nasopharynx
- larynx and vocal cords are pulled upward
- epiglottis swings downward
- UES relaxes
- pharynx muscles contract
- peristaltic wave initiates
Describe the esophageal phase of esophageal motor activity (3)
- UES constricts
- peristaltic wave below UES (primary peristalsis)
- if insufficient to clear food bolus, secondary peristalsis begins at the site of distension
Describe the primary wave of esophageal motor activity
- starts at a region close to the UES
- intention is to sweep the contents from the esophagus down to the stomach
- if the wave doesn’t work and it requires additional contraction, at the site of distension, another secondary wave is initiated
The secondary wave of esophageal motor activity (secondary peristalsis) is stimulated by what?
distension
The coordination of peristalsis involves 3 primary neurotransmitters - what are they? What else can coordinate/control the waves of peristalsis?
Ach (contraction of circular muscle), NO/VIP (relaxation of circular muscle)
- chemical receptors can also stimulate the secondary peristaltic wave (Done so via sensation of low pH)
- distension also stimulates the secondary wave
Bottom line: peristaltic wave utilizes coordinated chemical and mechanical influences and uses both contraction and relaxation in order to move the food
What is GERD?
characterized by reflux of the gastric contents into the esophgaus; this can lead to inflammation of the mucosal surface of the esophagus (esophagitis)
What are 5 possible causes of the initial esophageal lesion that may cause a cycle of esophageal injury
- delayed gastric empyting
- increased frequency of transient LES relaxations
- increased acidity
- loss of secondary peristalsis following transient LES relaxations
- decreased LES tone
Tell me the elements of the esophageal injury cycle
scar > incompetent LES > recurrent injury that leads to:
- Barrett’s esophagus then cancer
- stricture, pain, obstruction, perforation
GERD can result from a LES that relaxes when it shouldn’t. What might cause this? (think about a NT)
excess or uncontrolled release of NO that leads to too much relaxation
Describe Barrett’s esophagus: how it presents and what it’s caused by/linked with
- characterized by the replacement of squamous epithelial cells with columnar epithelial cells, giving the epithelial surface a dark red appearance as compared to the light pink normal epithelium it should be
- has been associated with an increased risk of esophageal cancer
- often linked with GERD damage
The migrating motor complex is gastric motor activity associated with what time interval?
initiated about every 90 min to 2 hours (until we eat)
What are the 3 primary gastric motor activities? Describe them in general terms
- storing: reservoir function in which the stomach fills and stores contents (tonic contractions)
- churning: mixing and initiation of digestion (phasic contractions)
- emptying: delivery of food to duodenum
Gastric storing/filling involves 2 steps - what are they?
- receptive relaxation
2. gastric accommodation
Describe some of the key traits for the receptive relaxation step of gastric storing/filling
- vagovagal reflex
- initiated by swallowing
- relaxation in anticipation of food
- relaxation of LES and proximal stomach
- noncholinergic and nonadrenergic
- rise in gastric volume but no rise in pressure
Describe some key traits of the gastric accommodation phase of gastric storing/filling
- stomach relaxation in response to gastric filling
- dilation of fundus
- primarily regulated by ENS
- modulated by vagus nerve
- increase in volume without increase in pressure
Name the 3 main actions involved in gastric churning
- propulsion
- retropulsion
- grinding
Describe the propulsion part of gastric churning
- movement of contents toward the antrum/pylorus
- initiated by pacemaker cells near the greater curvature
- pylorus is closed
Describe retropulsion utilized in gastric churning
pulverization and shearing of food particles
Describe the grinding component of gastric churning
- food is trapped in antrum
- products smaller than 2 mm passes through pylorus
- particles larger than 2 mm will eventually pass into duodenum during interdigestive period (approx. 2 hours later)
Rate of gastric emptying depends on what?
the content of the ingested material
Control of gastric emptying rate is controlled how?
via hormones and neuronal regulation
List 3 hormones involved in controlling gastric emptying rate
secretin, CCK, gastrin
List 4 NT that control rate of gastric emptying
Ach, NO, VIP, 5HT
HCl in the duodenum acts as a stimulus for gastric emptying - tell me what mediates this (hormone) and what the result is
secretin - impaired gastric emptying
Fat in the duodenum acts as a stimulus for gastric emptying - tell me what mediates this (hormone) and what the result is
CCK - impaired gastric emptying
Protein in the stomach acts as a stimulus for gastric emptying - tell me what mediates this (hormone) and what the result is
gastrin - impaired gastric emptying
Duodenal distension acts as a stimulus for gastric emptying - tell me what mediates this (system) and what the result is
ENS - impaired gastric emptying
Vagal stimulation has an effect on gastric emptying - tell me what 5 things mediate this effect and what the results of these mediators are
Ach, opioid, 5HT - impaired gastric emptying
NO, VIP - promotes gastric emptying
Describe some of the functions of secretin as related to gastric emptying
protects GI tract from acidic environment of the stomach; impairs gastric emptying to let the duodenum prepare for acidic contents
Tell me why CCK gets released and what its main roles are in gastric emptying
released in response to fat - delays emptying, keeps the stomach in the grinding/propulsion phase so the stomach can break down fat as well as possible and absorb it (abstract calories)
Very potent
What is gastroparesis?
delayed gastric emptying
- frequently associated with impairments of the pyloric region or pyloric sphincter itself as seen with poorly controlled diabetes mellitus or infantile pyloric stenosis
Define emesis, tell me what symptoms may precede it and what the overall concept is regarding how the process plays out
- expulsion of gastric and duodenal contents from the GI tract via the mouth
- preceded by: nausea, tachycardia, dizziness, sweating, mydriasis, retching, increased saliva production
- when you do stimulate an emetic response, we use the mechanical activity of the stomach and duodenum to expel the contents (mechanical activity) – however, the esophagus does not contract (esophagus actually relaxes)! We also recruit abdominal muscles to help increase pressure to push food up. Body tries to protect itself by increasing salivary production and production of bicarb and mucin to help protect the mouth and esophagus from the acidic content.
Name the 4 key NT involved in emesis
- SEROTONIN (5HT receptors)
- dopamine (D2 receptors)
- Ach (muscarinic receptors)
- histamine
Describe the general appearance of the mucosal surface of the stomach
it is highly invaginated, full of deep pits called gastric glands
parietal cells secrete which 2 products
hydrochloric acid (HCl) and intrinsic factor (IF)
Chief cells secrete what major product?
pepsinogen
Superficial epithelial cells secrete which two major products?
Mucus and bicarbonate
ECL cells secrete which major product?
histamine
G cells secrete which major product?
Gastrin
Nerve cells secrete which major product that influences gastric function?
Ach
D cells secrete which major product?
somatostatin
Parietal cells secrete hydrochloric acid (HCl) - please name its 3 functions
protein digestion, sterilization, nutrient absorption
important for activation of proteases, nutrient absorption and setting up a sterile environment
Parietal cells secrete intrinsic factor (IF) - please tell me its primary function
vitamin B12 absorption
chief cells of the stomach secrete pepsinogen - tell me its primary function
protein digestion
superficial epithelial cells secrete mucus and bicarbonate and they function in doing what?
gastroprotection - keeps the stomach from being damaged from the harsh environment used to breakdown food
ECL cells secrete histamine - what is its primary function in the stomach?
promotes HCl secretion
G cells secrete gastrin - what is its primary function in the stomach?
promotes HCl secretion
nerve cells secrete Ach - what are its 3 primary functions in the stomach?
promote mucus secretion, promote bicarbonate secretion, promote HCl secretion
D cells secrete somatostatin - what is its primary function in the stomach?
suppresses HCl secretion
Does the cardiac portion of the stomach contain parietal cells?
no
The body of the stomach contains 4 kinds of cells - what are they?
parietal cells, chief cells, neck cells, enterochromaffin like cells (ECL)
The antrum of the stomach contains 2 types of cells, but 3 different ones - name them
chief cells, endocrine cells (G cells and D cells)
Superficial epithelial cells are found where in the stomach?
everywhere
Why aren’t parietal cells found in the cardiac portion of the stomach?
because they would be very damaging to esophageal cells because they produce acid
What portion of the stomach is the key site of endocrine secretion?
the antrum
The cells that make up the gastric glands of the stomach secrete about how much isotonic fluid per day?
2 liters
What are the two fundamental types of secretions from the stomach?
- Na-rich basal secretion from non-parietal cells
2. H-rich stimulated secretion from parietal cells
Describe the 5 functions of gastric acid (HCl)
- protein digesetion, conversion of pepsinogen to pepsin
- provide sterile environment
- prevent bacterial and fungal growth
- facilitate absorption
- promote bile and pancreatic enzyme flow
Which cell type of the stomach represents the final common pathway for acid secretion?
parietal cell
Acid secretion in the stomach is regulated DIRECTLY through which 3 pathways?
- paracrine pathways (histamine)
- endocrine pathways (gastrin)
- neuronal pathways (Ach)
Describe how Ach/neuronal pathways have an effect on gastric secretion regulation DIRECTLY
Ach serves as a stimulation for secretion
describe how gastrin/endocrine pathways have an effect on gastric secretion regulation DIRECTLY
gastrin coming from G cells in the antrum of the stomach will bind to the parietal cell, stimulate receptors and promote acid secretion
Describe how histamine/paracrine pathways have an effect on gastric secretion regulation DIRECTLY
histamine is a paracrine regulator coming from ECL cells - it binds the receptors on the surface and promotes acid secretion
What role does PGE2 (prostaglandin) play in regulating gastric secretions DIRECTLY?
PGE2 is a prostaglandin paracrine regulator that turns off signaling at the surface to shut down acid secretion
PGE2 and histamine receptors converge on the same paracrine pathway (both G coupled protein receptors) and one stimulates while the other inhibits gastric secretions
Acid secretion (HCl) from the stomach can be INDIRECTLY regulated through which two pathways?
endocrine (gastrin, somatostatin)
neuronal (Ach)
*both Ach and gastrin regulate the ECL cell - directly and indirectly! They bind the parietal cell and histamine cell and promote acid secretion
What does somatostatin do to gastric acid secretion levels? Where does it come from?
Secreted by D cells - acts as a negative regulator
*if pH gets too low, D cells are stimulated to release somatostatin to help turn off the system
What is haptocorrin? What are its functions in gastric secretions? What is intrinsic factor and where does it come in to play? (think about a specific vitamin’s absorption)
Haptocorrin is a protein released by the salivary glands and it complexes with vitamin B12 once it is released from food particles in the stomach
Haptocorrin/B12 complex reaches the duodenum and haptocorrin gets degraded
From there, B12 complexes with intrinsic factor (IF) to be absorbed in the ileum
What is pepsinogen? What stimulates its secretion? Where does it come from?
- chief cells are the primary secretory cells of pepsinogen
- Ach is the main stimulus for secretion of pepsinogen
- other stimuli for its secretion: gastrin, CCK, histamine, secretin, VIP, NE, PG
- neck cells also secrete pepsinogen
- 8 different isoforms (group 1 from chief, group 2 from neck)
What does one need to activate pepsinogen?
an acidic environment!!!!
What are 2 protective factors found in gastric secretions? What are they made of?
mucus: mucin, phospholipids, electrolytes, water
bicarbonate
Describe 4 modes of protection against gastric secretion acidity
- physical barrier
- chief and parietal cell membranes are highly resistant
- high pH inactivates pepsins
- buffering capacity
What 2 systems regulate the secretion of protective factors in the stomach?
neurocrine (Ach)
paracrine (prostaglandins)
Describe the 3 key roles of prostaglandins in protecting from gastric secretions
- mucus and bicarb secretion
- suppression of HCl secretion
- increased gastric blood flow
List the 4 key gastric secretions
Acid (HCl)
pepsinogen
intrinsic factor
mucus
differentiate between gastritis and ulcers (both types of acid-peptic disease)
- gastritis is infiltration of inflammatory cells without a break in the mucosal barrier
- ulcers result in a breakthrough of the mucosal lining
List 10 of the primary causes of acid-peptic disease
- increased number of parietal cells
- high serum gastrin levels
- loss of acid-mediated negative feedback on gastrin secretion
- rapid gastric empyting
- H. pylori infeciton
- non steroidal antiflammatory drug use
- cigarette smoking
- alcohol use
- decreased mucosal bicarbonate secretion
- GERD
HCl in the duodenum stimulates secretin to do what?
impair gastric emptying
Fat in the duodenum stimulates CCK to do what?
impair gastric emptying
protein in the stomach stimulates gastrin to do what?
impair gastric emptying
duodenal distension stimulates the ENS to do what?
impair gastric emptying
Vagal stimulation to Ach, opioids, and 5HT does what?
impairs gastric emptying
Vagal stimulation to NO and VIP does what?
promotes gastric emptying
H pylori causes ulcers how?
lets out urease! Damages the cells!
Pancreatic secretions have 2 roles, in general. What are they?
- protective roles: bicarb (neutralizes acid) and mucus (coats surfaces)
- digestive roles: enzymes
Name the 3 major cell types found in the pancreas
acinar cells
duct cells
goblet cells
Tell me 3 important things about the acinar cells of the pancreas
- protein synthesizing cells (have very advanced ER)
- secretes digestive enzymes
- secretes fluids
Tell me the 3 functions of duct cells in the pancreas
- HCO3 secretion
- ion transport
- fluid transport
Tell me the primary role of goblet cells in the pancreas and the 4 results of this
- secretes mucin which:
1. lubricates
2. hydrates
3. protects
4. immune function
There are 6 pancreatic digestive enzymes secreted in an inactive form that work to digest proteins. Which one is the most important one to know?
trypsinogen
Name 4 of the most important ACTIVE pancreatic digestive enzymes and tell me what each does
- alpha amylase - carb digestion
- lipase - fat digestion
- colipase - fat digestion
- trypsin inhibitor - inhibits trypsin (which digests proteins)
What are two major regulators of stimulation of fluid and enzyme secretion in the pancreatic acinar cells?
Ach and CCK
How does CCK impact secretion of fluids and enzymes from the pancreatic acinar cells?
promotes fluid and enzyme secretion by causing secretion of Na, Cl (water follows)
***when CCK levels get too high, it actually turns off pancreatic secretions
Tell me 4 primary roles of CCK in the GI tract
- acts on gallbladder to stimulate contraction
- acts on the pancreas to stimulate acinar secretion
- acts on the stomach to reduce emptying
- acts on the sphincter of Oddi to cause relaxation
**overall: aids in digestion of macromolecules and matches nutrient delivery to digestive and absorptive capacity
What are 3 protective mechanisms found in the acinus to prevent activation of digestive enzymes
- most are inactive
- vesicles contain a trypsin inhibitor
- low pH of vesicle prevents enzyme activation
What important enzyme is used to convert trypsinogen to trypsin? where does this happen?
enteropeptidase in the duodenum (normally)
**if the concentration is high enough it will auto-activate!
What are the primary methods of protection in the duodenum?
- bicarb production
2. secretin - stimulates pancreatic ducts to secrete bicarb (Activate CFTR protein and exchange Cl for bicarb)
Secretin negative regulates acid secretion in 3 ways - describe them
- increases release of somatostatin
- decreases gastrin secretion
- decreases proton pump expression
Describe what happens in the interdigestive phase in terms of of pancreatic secretions (2)
- pancreatic secretions in this phase parallel the migrating motor complex
-Therefore pancreatic secretions parallel motility, secretion is highest during
intestinal contractility.
Describe the 3 regulators of the cyclical pattern of pancreatic secretion during the interdigestive phase
- stimulation by parasympathetic pathways
- stimulation by CCK
- inhibition by alpha adrenergic input, somatostatin and peptide YY
Describe what happens in the fed state in terms of pancreatic secretions (2)
During the fed state there is a 5 -20 fold increase in
pancreatic secretions.
The spike in secretion is primarily regulated by CCK, however multiple signals increase pancreatic secretions (redundancy).
Name the 3 phases of pancreatic secretions
cephalic
gastric
intestinal
Tell me the major stimulants for, the regulation pathway, and the % of max enzyme secretion for the cephalic phase of pancreatic secretions
sight, sell, taste, mastication
vagal pathways
25%
Tell me the major stimulants for, the regulation pathway, and the % of max enzyme secretion for the gastric phase of pancreatic secretions
distension, gastrin, peptides, peptones
vagal/gastrin pathways
10-20%
Tell me the major stimulants for, the regulation pathway, and the % of max enzyme secretion for the intestinal phase of pancreatic secretions
amino acids, fatty acids, H+
CCK, secretin, enteropancreatic reflexes
50-80%
What is the primary hormone used to stimulate pancreatic enzyme secretion?
CCK
What is pancreatitis?
inflammation of the pancreas
Describe the key traits of acute pancreatitis
- associated with alcohol or obstruction
- autodigestion
- inflammatory mediators released and damage to other tissues
Chronic pancreatitis
- continued damage
- alcohol abuse
What 2 things can pancreatitis lead to?
cancer, malabsorption syndrome
What are the 2 primary metabolic functions of the liver and gallbladder
energy metabolism (carbs, fats, amino acids, protein), detoxification
What are the 3 general functions of the liver and gallbladder?
metabolic, excretory, storage/transport
The excretory functions of the liver and gallbladder involve what products?
lipid soluble waste products
describe the relationship of the circulation of the liver with the GI tract
a. 70% of blood from portal vein
b. Initial site where materials
absorbed by the GI tract are
processed by the liver
first pass effect
Tell me 3 anatomical features which increase small intestine surface area
a. circular folds
b. villi (mucosa & submucosa)
c. microvilli (intestinal cells)
The surface epithelium of the small intestine contains 5 different cell types - name them
absorptive enterocytes
goblet cells
secretory enterocytes
endocrine cells
stem cells
Hepatocytes serve one very critical function in the liver in terms of anatomical relationships - what is that?
they act as an interface between blood and bile
Name the 4 primary cell types of the liver
hepatocytes, kupffer cells, endothelial cells, stellate cells
3 things to know about hepatocytes
- functional cells of liver
- polarized epithelial cell
- interface blood and bile
2 important traits of kupffer cells of the liver
- phagocytic macrophages (host defense)
- exposed to portal blood
Describe the endothelial cells of the liver
- large pores between cells (fenestrae)
- minimal basement membrane
2 functions of stellate cells in the liver
- regulate flow of blood
- constituents to the hepatocytes
Name the 4 key steps in the hepatocyte generalized biotransformation process
uptake, transport, biotransformation, secretion
Describe what happens during the uptake step of hepatocytes prior to biotransformation
- import of compound across basolateral membrane
Describe what happens during the transport step of hepatocytes prior to biotransformation
intracellular transport - movements can be directed by binding proteins
What happens in biotransformation of hepatocytes? (generally)
chemical modification or degradation
What happens during the secretion step of hepatocytes after biotransformation?
- secretes products across the apical or basolateral membrane
General function of hepatocytes
need to take things up from the blood - they sometimes diffuse and sometimes use active transport
The products secreted during biotransformation in the liver are secreted where and how?
secreted into the blood or bile dependent on the transporters available on the surface, as well as the lipid or water solubility of the compound
lipid soluble»_space; bile
water soluble»_space; blood
Name the 4 different modes of uptake during biotransformation in hepatocytes
- free diffusion
- Na-taurocholate co-transporting polypeptide (NCTP)
- organic anion transport protein (OATP)
- bilitranslocase (BT)
metabolism of a certain compound is changed by changes in uptake
Bile salt transport during biotransformation can occur via 3 different carrier proteins - name them
- dihydrodiol dehydrogenase
- glutathione-s-transferase B
- fatty acid binding protein
How many phases are there in biotransformation in hepatocytes?
two
Phase 1 of biotransformation can involve what 3 types of reactions?
oxidation, reduction, hydrolysis
expose a functional group on the compound to prepare it for phase 2
Phase 2 of biotransformation (conjugation) can involve what 3 types of reactions?
glucuronidation, sulfation, acetylation
you like the compound to another molecule
What is the general reason for conducting biotransformation reactions in hepatocytes?
increase the hydrophilicity of the molecule
How much bile is secreted each day? from where?
liver 900 ml/day
450ml/day concentrated by gallbladder
450 ml/day secreted by duodenum
List the 7 components of bile and tell me the two most important ones
BILE ACIDS BILE SALTS cholesterol phospholipids immunoglobulin A electrolytes waste products (drug metabolites, bile pigments)
Do bile acids undergo biotransformation?
some leave the liver as primary bile acids, some undergo biotransformation
If a bile acid leaves the liver as a primary bile acid, what can change it into a secondary bile acid?
enteric bacteria
What happens when a bile acid undergoes biotransformation?
it is conjugated - a large, bulky group is put on it to make it more polar and water soluble so it can be secreted into the duodenum (made into a bile salt)
What are some important things to know about enterohepatic circulation of bile salts and acids?
- liver secretes 12-36g/day of bile salts from cholesterol
- liver makes 600 mg/day: we lose 600 mg per day in feces
- we must RECYCLE 95% of our bile acids***
- small intestines (ileum) utilizes passive and active transport mechanisms to recycle bile acids
What are the roles of CCK and somatostatin on bile secretion?
CCK promotes gallbladder contraction and causes relaxation of the sphincter to promote bile flow
somatostatin is a key negative regulator of bile secretion
Importance of portal hypertension: what it is and what 4 consequences of it are
sign of liver dysfunction; high blood pressure in the portal venous system
- varices, splenomegaly, ascites, hepatic encephalopathy
Each individual enterocyte of the small intestine has an anatomical feature that helps to increase the surface area and absorptive qualities there- what is it and what does it form in conjunction with all of those around it?
each enterocyte has a microvilli - together it forms the brush border, which has a high level of expression of enzymes and transporters for nutrient absorption
The Brunner’s gland in the duodenum is very important for 2 main cellular secretions. Tell me which 4 things positively regulate its secretions and which system negatively regulates.
positive regulation: chyme, ENS, CCK, secretin
negative regulation: sympathetics
The Brunner’s glands of the duodenum contains epithelial cells that secrete which two important substances? Tell me each of their functions
mucus - protect mucosa from acid
bicarb - neutralize acid
The crypts of Lieberkuhn and villi throughout the intestine work together to secrete a number of different substances in the small intestine. Tell me which 4 things act as positive regulators for their secretions and which system acts as a negative regulator.
positive regulators: chyme, CCK, secretin, ENS
negative regulation: sympathetics
The crypts of Lieberkuhn and villi throughout the intestine work together to secrete a number of different substances in the small intestine. Tell me which primary cell types secrete their major products.
goblet cells
secretory enterocytes
absorptive enteroctyes
Goblet cells of the crypts of Lieberkuhn and villi throughout the smalld intestine secrete what substance? What’s its function?
mucus - lubricate and protect
Secretory enterocytes of the crypts of Lieberkuhn and villi throughout the small intestine secrete what substances? What are their functions?
H20 and electrolytes - used for absorption (everything but fats)
Absorptive enterocytes of the crypts of Lieberkuhn and villi throughout the small intestine secrete what substances? What are they used for, collectively?
expression of peptidases, sucrase, maltase, lactase, lipase, transporters - all used to help digest and absorb nutrients
What is one major stimulus for intestinal secretions that one might over look???
mechanical distension!
List the 3 primary regulators of GI smooth muscle in the small intestine (hint: same for other areas of the GI tract!)
Ach - stimulates
VIP - inhibits
NO - inhibits
List/describe the 3 types of small intestine motility
- migrating motor complex - interdigestive period (starts to dissipate as you move down the tract)
- segmental contractions - mixing to facilitate digestion
- peristaltic contractions - moving to facilitate digestion and propel contents downward
Tell me what the migrating motor complex is
waves of contraction (Depolarization/Repolarization) that sweep over the GI tract
Tell me the importance of distension in motility of the small intestine
distension triggers both proximal and distal peristaltic contractions
the contractions distal to the site of distension are relayed as reflexes
Reflexes are very important in the motility of the small intestine. Tell me about 2 key reflexes used to regulate small intestine functioning.
- distension of the stomach, duodenum, jejunum, and ileum is a key stimulus of peristaltic contractions in the small intestine
- - gastroenteric (Colic) reflex
- - gastroileal reflex
- -both are a way of feeding forward and prepping for more food content downstream - ileocecal sphincter regulates emptying of intestinal contents into the cecum
- - distension of the cecum inhibits relaxation of the sphincter
- - inhibition is mediate through ENS and sympathetics
- - this is a way of feeding back
Describe some of the key anatomical features of the large intestine
has both circular and longitudinal muscle like in the rest of the GI tract, but the longitudinal muscle here has 3 bands
What is the purpose of the 3 bands present in the longitudinal muscle of the large intestine?
sets up a structure that further facilitates mixing and allows for even better absorption of water
What’s one huge difference between the small and large intestine in terms of anatomical structure?
the large intestine has no villi, but it has more goblet cells and therefore produces a lot of mucus
The crypts of Lieberkuhn throughout the large intestine are important in secreting 3 primary substances. Tell me which 3 things/systems act as positive regulators of its secretions and which system acts as a negative regulator
positive regulation: mechanical**, PNS, ENS
negative regulation: sympathetics
The crypts of Lieberkuhn throughout the large intestine are important in secreting 3 primary substances. Tell me the 3 major types of cells found there.
goblet cells
secretory enterocytes
absorptive enterocytes
Goblet cells of the crypts of Lieberkuhn throughout the large intestine are responsible for secreting what? What does it do?
mucus - used for lubrication and protection
Secretory enterocytes of the crypts of Lieberkuhn throughout the large intestine are responsible for secreting what 2 substances? What are their functions?
H20 and electrolytes - used for EXCRETION of H20 and electrolytes
The absorptive enterocytes of the crypts of Lieberkuhn throughout the large intestine function in doing what?
absorbing H20 and electrolytes
Tell me about the mixing motility of the large intestine. How does it happen? What happens? What controls it?
Mixing movements are mediated by contraction of circular smooth muscle
resulting in intense spaced constriction. Longitudinal also constricts causing
a bulging appearance. Done by non-propulsive segmentation.
Propulsive movements and reflex control are important in the large intestine for motility. Describe to me the 3 different propulsive movement and reflex types of motility that happen here. Tell me the physical results and key impact of sympathetic stimulation.
- Propulsive movements (mass peristalsis/movements) moves contents toward rectum approximately 3x/day (up to 10x/day).
- Mass movements start where there is distension which initiates a coloncolonic reflex.
- Distension in the stomach (gastrocolic reflex) and duodenum (duodenalcolic reflex) will initiate mass movements.
- contraction initiated at the site of distension and loss of haustrations
- sympathetic stimulation relaxes portions of the colon distal to the distension
There are four key features/steps to the defecation reflex. The first one is the intrinsic reflex. Describe what happens during this reflex.
Distension initiates signals to ENS of the myenteric plexus. This initiates a peristaltic wave in the descending colon, sigmoid colon, and rectum forcing feces toward the anus.
Internal anal sphincter relaxes (NO, VIP).
Intrinsic reflex is relatively weak. This allows you to maintain control of the external anal sphincter and keep it closed. Regardless, it increases the pressure inside.
There are four key features/steps to the defecation reflex. Name them
- intrinsic reflex
- parasympathetic defecation reflex
- additional afferent signals
- desired defecation
There are four key features/steps to the defecation reflex. Describe the parasympathetic defecation reflex, step two.
Signals from the rectum are relayed to the spinal cord and back to the descending colon, sigmoid colon, and rectum forcing feces toward the anus mediated through parasympathetic nerves.
Further increases the pressure and you get a further relaxation of the IAS and maintaining tone of the EAS.
There are four key features/steps to the defecation reflex. Describe the additional afferent signal step (3).
Additional afferent signals from the rectum to the spinal cord also initiate a deep breath, closure of the glottis, and contraction of the abdominal wall muscles to force fecal contents downward.
At the same time the pelvic floor relaxes and pulls the anal ring outward.
There are four key features/steps to the defecation reflex. Describe the desired defecation step.
Results in conscious relaxation of the external anal sphincter and evacuation of the feces.
When it comes to the process of defecation in the large intestine, tell me 3 key take-home points regarding stimulation/control
High involvement of parasympathetics here
ENS intrinsic motor patterns are weak compared to parasympathetics
At beginning and end of GI tract we have striated muscle under voluntary control!
Does nutrient absorption take place in the large intestine?
nope
In terms of the natural microbiota of the gut, what could one say about the distribution of bacteria?
In general, as the distance from the stomach increases the concentration of bacteria increases
The distribution of several species is known, such as E. Coli and bacteroides as predominant species in the colon versus the small intestine.
Tell me the 4 factors that impact the growth of GI bacteria
- gastrointestinal secretions: saliva, acid, fluid/electrolytes, bile
- mucosal immunity
- intestinal motility*****
- pharmacological agents: antibiotics, cancer-chemotherapeutics, immunosuppressants
Tell me the 5 functions of intestinal bacteria
- conversion of primary to secondary bile acids
- deconjugation of compounds conjugated in the liver: drugs, bile salts (that would occur during biotransformation)
- nutrient salvage
- detoxification
- suppression of pathogenic organisms
Tell me what kind of carbs monosaccharides are, if they are digested or absorbed and what 3 examples are
Monomers
Don’t need to be digested
Absorbed as is
Fructose, galactose, glucose
Tell me what kind of carbs oligosaccharides are, if they need to be digested or if they get absorbed, and provide 2 examples
Short polymers that must be digested and cannot be absorbed
Sucrose, lactose
Tell me what kind of carbs polysaccharides are, whether they need to be digested or not, if they can be absorbed, and give me some examples
Long polymers that must be digested and cannot be absorbed
45-60% of carbs, as well as amylose and amylopectin
Tell me what kind of carb fiber is and whether it can be digested or absorbed, as well as an example of a fiber
polymers that cannot be digested or absorbed by our gut
cellulose (glucose polymer)
Give me a brief overview of the digestion of carbs
polysaccharides broken down by alpha amylase (from pancreas) in the lumen of the intestine»_space;» oligosaccharides broken down by lactase/maltase/isomalatase in the brush border of the intestine»_space;» monosaccharides absorbed
note that whichever form you eat enters the process and goes from there
Knowing how carbs are digested, what is one key thing to point out about the cells involved in digestion?
enterocytes not only help with absorption but they also play a role in the digestion!
What is the primary site of carbohydrate absorption?
the duodenum
What 3 major transporters are expressed in the duodenum that function to facilitate monosaccharide absorption? Tell me what each is responsible for transporting
SGLT1 - glucose and galactose/co-transported with sodium (nutrient transport + sodium absorption)
GLUT5 - fructose transporter
GLUT2 - glucose, galactose, and fructose
What is one key difference between carbohydrate and protein digestion/absorption?
proteins don’t need to be broken down all the way to amino acids in order to be absorbed!
This makes the protein digestion/absorption more efficient
Outline the general process of protein digestion
- proteins from diet are broken down by pepsin (from chief cells) in the lumen of the stomach to oligopeptides
- oligopeptides are broken down via trypsin (from pancreas) and other enzymes into smaller oligopeptides or amino acids in the lumen of the duodenum before being absorbed, or they can be absorbed without breaking down any further
What are the 2 amino acid transporters used to absorb proteins in the intestine?
PEPT1 and B - both move amino acids and sodium (much like SGLT1, they are sodium/nutrient transporters)
Outline the process of lipid digestion in the GI tract
- lipids ingested as triglycerides or cholesterol are broken down via lingual lipase, gastric lipase, and emulsification in the lumen of the stomach
- triglycerides, diglycerides, free fatty acids, cholesterol are broken down and emulsified with bile via pancreatic lipase, co-lipase, and emulsification in the lumen of the duodenum
- absorption occurs
What’s one key aspect to lipid digestion/absorption that has to occur?
emulsification!
What is the key site for fat emulsification?
the stomach
What is emulsification?
breaking fat into smaller pieces, physically, without chemical means
mix in bile to form a micelle that allows the fat to be more water soluble so it can be solubilized in the lumen of the intestine
emulsion lipid droplet + lipases and bile acids make small lipid droplets, which are acted on by lipases + bile acids to make micelles
What are lingual and gastric lipase?
unique enzymes that resist low pH in the stomach
and digestion via pepsin, however they are inactivated by pancreatic proteases
and alkaline conditions of the duodenum
What is the most potent nutrient stimulus for starting lipid digestion and absorption?
CCK - works by promoting gallbladder contraction, acinar secretion in the pancreas, and relaxation of the sphincter of oddi
What is the role of colipase in lipid digestion/absorption?
colipase serves as a regulatory molecule - it activates pancreatic lipase and targets it to (anchors it to) the fatty droplet (emulsified fat)
Describe to me the importance of delivery of lipid products to enterocytes via the use of micelles (hint: think of some major nutrients that utilize micelles for their absorption)
In addition to lipids, fat soluble vitamins partition into the micelle. –Vitamins A, D, E and K
if one cannot absorb fat due to some error in the process, one would be deficient in these vitamins
In terms of fat digestion and absorption, differentiate between the roles of the liver and pancreas
liver = fat absorption pancreas = fat digestion
We know that the duodenum is the primary site of fat absorption. Tell me how this works and what transporters/factors are used to do this - also tell me how cholesterol is absorbed, specifically
once entering the duodenum, there is a slight pH change that causes the micelle to fall apart - fats are moved across the membrane via passive and active transport
Cholesterol is absorbed via NPC1L1 proteins
once the enterocyte absorbs the lipids, it reassembles them into a package form (chylomicron)
How/where is vitamin B12 absorbed?
Vitamin B12 (cobalamin) is absorbed in the intestine via the help of intrinsic factor (secreted by gastric parietal cells) which is used to bind the B12 and a protein called haptocorrin to be brought into the duodenal membrane
duodenum breaks down haptocorrin and ileum absorbs IF and B12
Where is the highest expression of IF receptors? Why are they so important there?
Highest expression of the IF
receptor is found in the ileum
IF receptor is required to bind B12 and allow its absorption in the ileum
Where is vitamin B12 stored and secreted?
Vitamin B12 is stored in the
liver and secreted in the bile
Damage to either the mucosa of the stomach or the ileum can lead to B12 deficiency. Tell me how.
damage to parietal cells of gastric mucosa decreases amount of IF present
damage to mucosa of ileum will prevent absorption and receptor IF expression
Where is calcium absorbed? How is it absorbed?
Ca absorbed in duodenum – it moves down its concentration gradient across the apical membrane through a Ca channel
Expression of this channel is regulated at the transcriptional level by vitamin D
Vit D is a fat soluble vitamin so if Vit D synthesis/absorption issues exist, there will also be impairments of Ca absorption – b/c vit D regulates Ca absorption
Tell me about lactose intolerance in terms of symptoms and underlying pathological mechanism
Lactose intolerance
due to lactase
deficiency results in: cramps (gas) and diarrhea (change in osmotic pressure)
What is celiac sprue (absorption disorder)? What is its hallmark feature?
(Gluten-sensitive enteropathy): the loss of mature villous
duodenal and jejunal epithelium caused by ingestion of gluten (protein component of cereal grains) resulting in malabsorption and inflammation.
Estimated: 1/120 people
Hallmark: absence of villi
Immune process: lymphocytes attack the absorptive enterocytes - as the enterocytes die, the villi shrink
Tissues of the ileum contribute to what? Digestion or absorption?
both!
Where is the net absorption of potassium greatest? What about the net secretion?
net absorption - small intestine
net secretion - colon
Tell me about the mechanisms that permit intestinal absorption of sodium (hint: there are 4 primary transporters)
Sodium/potassium ATPase helps maintain the concentration gradient
B and SGLT1 are sodium/nutrient coupled channels - most active during a meal (fed state functionality)
sodium/hydrogen exchanger expressed throughout to let sodium in for H movement out
There is also a sodium channel that allows sodium in via movement down its concentration gradient
Tell me about the movement of chloride and bicarb in terms of absorption and secretion in the GI tract/intestines
they always move in opposite directions - there is a net secretion of bicarb and a net absorption of chloride, regardless of the location in the tract
Tell me the mechanisms behind intestinal absorption and secretion of chloride and bicarb, including which transporters are involved
Chloride moves to the apical membrane side of the enterocyte because there is a large sodium concentration there – leads to total chloride absorption (net) - moves via chloride/bicarb exchanger as bicarb moves out
Chloride is secreted via special transporters like CFTR that can be regulated through second messengers (Ca, cAMP)
Chloride secretion leads to water retention in the intestine
Tell me the mechanisms and transporters behind the absorption and secretion of potassium
Absorption through solvent drag in small intestine – moves with the water to a higher salt concentration
[K absorption = solvent drag]
In the colon – drawn to the negative charge in the lumen (Due to the secretion of bicarb there that makes it negative)
[K secretion = luminal negativity]
Continue to absorb sodium even when potassium is secreted via the sodium/potassium ATPase transporter
Tell me about the general mechanisms used to regulate electrolyte absorption and secretion in the GI tract
Open chloride channels and inhibit sodium exchanger – net secretion of fluid
Sodium chloride accumulates in lumen, water is drawn there, it is retained there
cAMP, cGMP, Ca
Promote fluid absorption with steroids - Regulate at transcription level (takes longer to respond) – but leads to upregulation of proteins that increases absorption of salts and therefore water
What 5 cateogories of factors can affect fluid absorption or secretion in the GI tract? Which ones do each?
Fluid secretion - neuronal, paracrine/immune, bacteria
Fluid absorption - endocrine, other (hormonal)
There are 3 neuronal agents whose actions result in fluid secretion from the large and small intestine. Tell me their names, their mechanism of action and the transporters involved
Ach, VIP, 5HT (serotonin)
Work via second messenger generation
Stimulate CFTR, inhibit the Na/H exchanger
There are 2 paracrine/immune agents whose actions result in fluid secretion in the small and large intestine. Tell me their names, their mechanism of action and the transporters involved.
prostaglandin and histamine
Work via second messenger generation
Stimulate CFTR, inhibit Na/H exchanger
There are 2 bacterial agents whose actions result in fluid secretion in the small and large intestine. Tell me their names, their mechanism of action, and the transporters involved.
Cholera and E. coli
Work via second messenger generation
Stimulate CFTR, inhibit Na/H exchanger
There are 2 main kinds of endocrine agents whose actions result in fluid absorption in the GI tract. Tell me their names, mechanism of action, where each works and transporters involved
mineralcorticoids, glucocorticoids
Work via transcriptional regulation
Upregulation of Na channels and Na/K ATPase
Mineral = colon
Gluco = large and small intestine
Does somatostatin promote fluid secretion or fluid absorption? Where does it do this? Which transporter is involved?
fluid absorption in the large and small intestine - works on Na/H exchanger
What is diarrhea?
increase in the number of bowel movements or a decrease
in stool consistency
What are 4 causes of diarrhea?
a. increased intestinal secretion – if we promote/stimulate the chloride ion channel, we may cause too much water to go into the lumen and it can cause diarrhea
b. decreased intestinal absorption
c. increased osmotic load – present too much to intestine and colon, so it can’t fully absorb everything (i.e. glucose absorption deficiency in intestine would cause too much to presented in the colon, so water would be retained in the lumen of the colon)
d. abnormal intestinal motility – things are moving too quickly, so there isn’t enough time to absorb everything
What are the 2 types of diarrhea?
secretory and osmotic
What defines diarrhea as osmotic in nature?
diarrhea caused by a nonabsorbable nutrient – retain fluid in the lumen via change in osmotic pressure
What defines diarrhea as secretory in nature?
diarrhea caused by intestinal secretion of fluid
and electrolytes – when we’re stimulating the chloride channels and sodium/salt moves into the lumen and water follows (movement of fluid into the lumen rather than it being retained)
What is constipation?
infrequent or difficult evacuation of the feces
What are 5 different, possible mechanisms of constipation? (keep it general, give an example)
- Diet/lifestyle - fiber intake, fluid intake
- GI - cancer, hernia, inflammation
- Pharmacological - narcotics, laxative abuse, antacids
- Endocrine - diabetes, hypothyroidism, hyperparathyroidism
- Neurogenic - neuropathy, Parkinsons, paraplegia
What are 6 possible causes of osmotic diarrhea?
- Disaccharidase deficiency
- Pancreatic enzyme deficiency
- Nutrient-binding substances
- Loss of enterocytes
- Bacterial overgrowth
- Antacids
What are 3 possible causes of secretory diarrhea?
Enterotoxins
Inflammatory cytokines
Tumor (VIP, 5-HT)
What are 2 things that can causes both secretory and/or osmotic diarrhea?
infectious disease
inflammatory conditions
What are the 5 primary functions of blood?
- nutrient transport
- thermoregulation (has high capacity to hold heat)
- defense (immune system)
- maintenance of water and electrolyte balance (necessary for cells to function properly)
- wound repair
What 4 kinds of things are transported in the blood?
Nutrients (glucose, amino acids, lipids)
Wastes (urea)
Gases (carbon dioxide an oxygen)
Hormones that regulate the functions of different cell types throughout the body
Describe the composition of blood and its relation to body weight and volume
Blood is about 7 – 8% of total body weight
Average volume of blood:
5 liters – women
5.5 liters - men
Buffy coat (WBC and platelets) separates a top liquid portion (plasma 58%) and formed elements (42%)
Describe the composition of the plasma - tell me how its pH is maintained and what primary proteins are present in the plasma
The composition of plasma is kept relatively constant. Liver replenishes plasma proteins and respiratory and kidneys maintain pH.
92% water by weight, proteins 7%, the rest is other solutes
proteins: albumin»_space; globulins»_space; fibrinogen»_space; regulatory proteins
other solutes: electrolytes, nutrients, resp. gases, waste
Describe the cells that make up the formed elements portion of the blood (42%) - 3 main types and examples of some
RBC»_space; platelets»_space; WBC
WBC are neutrophils (most), basophils (least), eosinophil, monocyte, lymphocyte
What are 3 types of granulocytes (polymorphonuclear leukocytes)
neutrophils, eosinophils, basophils that have dense granules in their cytoplasm
5 types of agranulocytes (mononuclear leukocytes)
NK cell mature B cell helper T cell suppressor T cell monocytes/macrophages
What is serum?
plasma without fibrinogen and other clotting factors
What are the plasma ion concentrations of Na and Ca?
1 mM of Na+ = 1 mEq/L Na+
1 mM of Ca2+ = 2 mEq/L Ca2+ (has 2 charges)
Plasma has largest concentration of Sodium for cations, largest concentration of anions is chloride ions
There is an equilibrium of charge, though.
Bicarb is another important anion in the plasma
What is the anion gap?
Anion gap is the concentrations of Anions normally unmeasured in basic metabolic chemistry panels. Typically, the anion gap is approx. 8-16
AG = Na+ − (Cl− + HCO3−)
What is one necessary element for ion concentration in any body fluid compartment?
concentrations of cations and anions must be equal
What is the anion gap calculation used for?
Useful for diagnosing metabolic acidosis
What happens to anion gap in metabolic acidosis?
Metabolic acidosis with an increased anion gap
Ketoacidosis, lactic acidosis, salicylate poisoning, etc. cause build up of organic anions
Increase acid in plasma is causes a decrease in [HCO3–]
The plasma constituents play a major role in what measure of the blood? What is the significance of this?
The plasma constituents play an important role in regulating the osmolality of plasma, which is directly proportional to the osmotic pressure.
Osmotic pressure and hydrostatic pressure (capillary pressure) regulate fluid movement across capillaries
What is an osmole?
moles of solute times the number of ions or particles upon its dissociation in solution (1 mol/L of NaCl = 2 osmol/L)
What is osmolality and what are the major determinants of it? (5)
Osmolality = Osmoles of solute/Kg of solvent
Major determinants of plasma osmolality (by virtue of their concentrations) are: Na+, Cl-, HCO3-, blood urea nitrogen (BUN), and glucose
(Reference range = 285 – 295 mOsm/Kg H2O)
What is the role of plasma proteins in osmotic pressure?
The molality of plasma is slightly higher than the molality of interstitial fluid because the plasma contains proteins (primarily albumin) that cannot cross the capillary membrane.
This leads to the force driving water into the vasculature (osmotic pressure).
What is albumin? What is its role in the blood? What happens if albumin levels drop?
Makes up approx 58% of plasma protein (approx. 3.4-4.7 g/dL)
Responsible for approx 70-80% of colloid osmotic pressure
Albumin also important as transporter of Free fatty acids, calcium, copper, steroid hormones, bilirubin, drugs
Loss of albumin leads to decreased oncotic pressure =
Edema
What are 3 general causes of hypoalbuminanemia?
decreased synthesis, increased volume of distribution, increased excretion/degradation
(specific examples in ppt)
What are 3 examples of important globulin proteins in the plasma? Tell me their functions
- Gamma-globulins
- Immunoglobulins (antibodies)
- Involved in immunity - Transferrin
- Free iron is toxic so this binds iron to allow for iron to be transported to tissues like the bone marrow for the production of erythrocytes - Haptoglobin
- Binds free hemoglobin that can enter the plasma after the lysis of erythrocytes (hemolysis)
- Transports it to the liver
What is hematopoiesis? How often does it happen and why?
Formation of all blood cell types - happens constantly
Formation of all blood cell types is called hematopoiesis
Most mature blood cells have a relatively short life span
Cells that leave the blood stream, or die need to be replaced
Must be continuously replaced by stem cells (the hematopoietic system is regulated by the functional needs)
What is the primary cell type utilized for hematopoeisis and where can we find it? What else is needed for this process to occur?
Stem cells are multipotent (can differentiate into any of the blood cells) and they can self renew
Postnatal hemopoiesis almost exclusively in BONE MARROW
Hematopoiesis requires sufficient supply of minerals (e.g., iron, cobalt, and copper) and vitamins (e.g., folic acid, vitamin B12, pyridoxine, ascorbic acid, and riboflavin);
Tell me about red blood cells (erythrocytes), in terms of function, shape, lifespan, and composition
Biconcave shape with no nucleus or other organelles
Glycolytic enzymes for ATP production (e.g. lactate dehydrogenase)
Shape allows:
- Increase in surface-to-volume ratio enhancing gas exchange
- Erythrocytes to be easily and reversibly deformable
Live for about 120 days
Hemoglobin accounts for 95% of intracellular protein
When hemolysis is elevated, what happens to plasma levels of lactate dehydrogenase?
Plasma normal has low levels of lactate dehydrogenase, but when hemolysis is elevated, plasma levels of lactate dehydrogenase significantly increase.
What is the significance of lactate dehydrogenase in the blood?
signifies hemolysis - normally isn’t present in the blood
Describe the structure of hemoglobin, as well as its 2 primary functions
Hemoglobin A (HbA) 95 % of hemoglobin type in adults
- 4 globin chains
- 2α-globin chains (CO2 binding site)
- 2β-globin chains
Each is bound to a heme moiety containing iron (binding site of O2)
Functions to carry O2 to tissues and CO2 to the lungs
Important acid-base buffer
—-Histidine residues in globin can accept H+ as blood becomes acidic
What is erythropoeisis? How often does it occur? Why is it regulated?
Formation of RBC
Approx. 200 billion new erythrocytes are made daily
Highly regulated to prevent:
Too few erythrocytes (anemia)
Too many erythrocytes (polycythemia)
Describe the progression of hematopoeitic cells to mature RBC. Tell me the 5 cell types along the way, characteristics of them and where the formation of each occurs.
[in the bone marrow]
1. hematopoietic stem cell to 2. erythroid progenitors via EPO to 3. erythroblasts with Hb accumulation, nuclear condensation, decreased cell size, loss of nucleus
to [in the bloodstream] to
4. immature RBC = reticulocytes to 5. mature RBC
Give me a very brief, simplified explanation of hematopoeisis and the changes that occur during it
Different cell types are formed – regulated through the production of different hematopoietic growth factors
Hematopoietic stem cell differentiates into myeloid lineage or lymphoid lineage
As cells become more differentiated, they lose some of their proliferative potential and when they are fully differentiated, they no longer proliferate
What is hemostasis? Tell me 3 major traits of it in general terms
Cessation of bleeding from a cut or severed vessel
Because adequate blood flow is essential for all vital functions, it is:
Rapid
Self-limiting
Reversible
What are the 5 systems that make utilize/carry out hemostasis?
- vascular system
- platelet system
- coagulation system
- anti-coagulation system
- fibrinolytic system
What are two possible consequences of a deficiency in any of the 5 hemostatic systems?
Hemorrhaging - Hemophilia and many other bleeding disorders
Thrombosis (inappropriate clot formation)
- Clot becomes too big and begins to significantly inhibit blood flow
- Clots form at inappropriate sites in the vasculature
- Clots embolize and block distant areas of vasculature
Do the 5 systems of hemostasis act alone or together?
These systems DO NOT function in isolation from each other and there are numerous points of interaction
Vasoconstriction is controlled by what 3 factors/systems? Tell me briefly how each works
Local factors: Release of local factors from damaged tissues immediately act to cause vasoconstriction
Activated platelets at site of injury release the vasoconstrictors thromboxane A2 and serotonin
Coagulation system produces thrombin, which induces blood vessel endothelial cells to produce and release endothelin - Endothelin binds to smooth muscle cells of the vasculature to induce contraction
Healthy vasculature has anti-platelet adhesion properties - describe 3 of them
Vascular endothelial cells release nitric oxide (NO) and prostacyclin (PGI2) - actively inhibit
NO and PGI2 also induce vasodilation
Negative surface on platelets and endothelial cells help to prevent adherence
Give me a brief overview of how the platelet system works
- platelet adhesion and activation
- platelet granule release
- platelet shape change
- platelet recruitment
- platelet plug formation/aggregation
As a platelet plug is formed, what are some key things that happen and what mediates them? (hint: think adherence, activation, recruitment, aggregation)
Adherence to site of vessel injury through cell surface glycoprotein receptors
Initiation of release of factors that further activate adherent platelets
Released factors also activate and recruit nearby platelets
The aggregation of platelets at injury form a platelet plug that reduces blood loss
What happens in initial platelet tethering? What protein is important during this?
Platelet glycoprotein receptor Ib (GPIb) binds exposed von Willebrand factor (vWf) to facilitate initial platelet tethering to site of injury.
Describe, in more specific terms, the role of platelet glycoprotein VI and the adhesion/activation that occurs with its action
Platelet glycoprotein VI (GPVI) binds to collagen at injury site to induce adhesion.
Adhesion induces initial activation of platelets.
- Shape change
- Release of Adenosine diphosphate (ADP), serotonin, and thromboxane A2 (TXA2)
Platelet activation also leads to a conformational change in the platelet glycoprotein receptor IIa/IIIb (GPIIa/IIIb), causing it to be able to bind fibrinogen
ADP, thrombin, and thromboxane A2 (TXA2) are important in amplification and activation of platelets in thrombosis as G protein-coupled receptors and ligands - tell me the role of each
ADP :
Released by activated platelets
Activates Purinergic P2Y12 receptor
Thrombin:
Produced by coagulation pathway
Activates protease activated receptors (PARs)
Thromboxane A2 (TXA2):
Released by activated platelets
Activates TXA2 receptors
Erythropoeisis levels can be effectively measured using what cell type?
reticulocytes
Erythropoeisis effectiveness can be measured via levels of reticulocytes. Tell me what high/low levels mean these cells mean for erythropoesis and why reticulocytes can be used to do this. What’s the normal level of reticulocytes in the circulation?
Reticulocytes circulate for about 24 -48 hours before loosing their residual organelles (mitochondria and ribosomes) thus becoming mature erythrocytes.
Normally 0.5-2.5% of RBCs in circulation are reticulocytes
An increase % of RBCs that are reticulocytes (recent increase in erythropoiesis)
Decrease in % of RBC’s that are reticulocytes (deficiency in erythropoiesis)
Where is erythropoietin made? What stimulates its production there?
In the kidneys -
Kidney senses O2 levels and produces erythropoietin when levels decrease
List 5 factors that decrease O2 delivery to the kidney
Low blood volume Low erythrocyte numbers Low functional hemoglobin Poor blood flow Pulmonary disease
What happens to EPO production in the kidney if oxygen levels are normal?
Negative feedback mechanism normally reduces erythropoietin levels when blood oxygen levels are within appropriate range
So, as blood becomes more oxygenated, EPO levels will decrease
What is a possible reason that an individual would have abnormally low reticulocyte numbers but high plasma erythropoietin levels?
If erythropoeisis isn’t functioning properly, you have less reticulocytes but you increase the level of EPO to try to compensate
What is the hematocrit? What are normal ranges for males/females?
(Hct): percent of the total volume of RBCs per total blood volume
Normal male (40 – 54 %) Normal female (36 – 48 %)
What are some reasons for an abnormally high hematocrit?
Polycythemia (elevated RBCs)
Polycythemia vera (a bone marrow disorder that leads to the hyperproliferation of progenitors)
Diseases that reduce blood oxygen levels
Dehydration (normal RBCs numbers in a reduced plasma volume – less water in the plasma)
What are some reasons for an abnormally low hematocrit?
Hypoproliferative diseases of the bone marrow
Nutrient deficiencies
Red blood cell lysis (hemolysis)
Bleeding
Overhydration
Name 3 Common Red blood cell measurements and tell me what each is (hint: think the letter M)
Mean Corpuscular Volume (MCV) - Single RBC volume
Mean corpuscular hemoglobin (MCH) - Hgb amount (picograms) in average RBC
Mean corpuscular hemoglobin concentration (MCHC) - Average Hgb concentration (g/dL) in a given volume of RBCs
Tell me about the normal destruction patterns of old erythrocytes in terms of how/where they are removed and how long they live
Normal lifespan of RBC is approx 120 days
90% of old and damaged erythrocytes are removed by phagocytosis by liver and spleen macrophages (extravascular hemolysis – occurs in the macrophages of the organs rather than the vasculature itself)
10% lyse in circulation (intravascular hemolysis)
Give me a brief synopsis of the breakdown of erythrocytes and the conservation of iron that takes place in extravascular hemolysis (hint: the Hb breaks down, so you should tell me how)
When the cells become damaged, they are taken up by macrophages and they are broken down
The Hb gets broken down into globin chains and they are released/reused – the heme molecule gest converted into biliverdin which can be converted to bilirubin
The porphyrin ring of the Hb will be converted to bilirubin and will be transported to the liver to be released into the duodenum»_space;> bilirubin > urobilinogen > stercobilin > out in feces or urobilinogen can go to kidneys and be excreted in the urine
The protein haptoglobin functions in the process of iron conservation. Tell me how. (Hint: remember iron can be broken down in 2 ways)
Hb → Kidney → Excreted in urine or precipitates in tubules; iron is lost to body
Hb + Haptoglobin (Hp)→ Hb/Hp complex → macrophages in the liver and spleen endocytose the complex; iron is conserved and reused
Tell me about the lifespan of haptoglobin, whether free or bound. Also tell me what haptoglobin binds to and why.
Free haptoglobin (Hb) ½-life is approx 5 days
Haptoglobin ½-life when bound to hemoglobin is approx 90 min.
Haptoglobin bound to hemoglobin allows for recycling of iron from heme
What is hemolytic anemia? What are 3 possible causes?
A decrease in RBCs due to an elevation in premature RBC destruction
Increased extravascular hemolysis
Increased intravascular hemolysis
Many different causes such as RBC membrane defects, immune disorders, infections, drugs
Describe 6 lab results that are indicative of hemolytic anemia
Elevated plasma LDH
Decreased plasma haptoglobin*
Free hemoglobin in blood (hemoglobinemia) and urine (hemoglobinuria)
Increased blood plasma bilirubin levels
Increased urine urobilinogen
Increased reticulocytes – want to replenish the damaged RBC
Name 3 classifications of anemia by cell size and hemoglobin levels and tell me the associated MCV values for each
microcytic (MCV 100)
Microcytic anemia - examples of this and what MCHC values are like
Iron deficiencies, chronic inflammation, thalassemia
Usually also low MCHC b/c you don’t produce enough Hb (considered microcytic hypochromic anemia)
Normocytic anemia - examples of when this occurs and what MCHC values are like
Can occur with hemolysis (hemolytic anemia) : Autoantibodies, malaria
Hypoproliferative diseases
Usually normal MCHC (normocytic normochromic anemia)
Macrocytic anemia - examples of when this occurs and what MCHC levels are like
Folic acid and vitamin B12 deficiencies
DNA replication synthesis defects
MCHC is variable
Tell me what platelets are, what they do, what they are made of, and how they work
thrombocytes that are key players in the cessation of bleeding (hemostasis).
Small nucleus free fragments of megakaryocytes that live for about 10 days
Destroyed in the liver and spleen by phagocytosis
Become activated when glycoproteins on their surface bind collagen and other factors at sites of injury
Activation involves shape changes and secretion of numerous factors that facilitate blood clot formation
What is the function of Thrombopoietin, aka TPO in thrombopoiesis? Where is it secreted from?
stimulates differentiation of megakaryocyte progenitor cells into immature megakaryocytes
secreted constitutively by liver and bone marrow
Outline the process of thrombopoesis (platelet formation) for me. (hint: start with TPO and end with regulation of TPO - 5 things to note including how many platelets are made)
Megakaryocyte-progenitor cells are stimulated to differentiate into immature megakaryocytes by thrombopoietin (TPO).
Megakaryocyte precursors undergo endomitosis (mitosis without cytoplasmic divisions) → large multinucleated (Megakaryocytes are the largest cells in the bone marrow).
Platelets then produced from cytoplasmic budding from megakaryocytes in bone marrow (100 billion platelets produced each day).
Each megakaryocytes can produce 100-1000 platelets.
Increases in platelet numbers causes a negative feedback of thrombopoiesis by binding to and degrading TPO.
Platelets release cytokines and two kinds of granules. Name the 2 kinds and what each set of granules are responsible for releasing. (hint: D3, A4)
- Dense granules:
ADP, serotonin, Ca - Alpha granules:
growth factors, coagulation proteins (fibrinogen, factor v), plasminogen activator inhibitor, heparin neutrailzing factor
As a whole, what are the 4 general functions of the various factors released by platelets?
Amplification of platelet activation and aggregation
Facilitation of coagulation (Factor V, fibrinogen)
Inhibition of anticoagulation system (heparin neutralizing factor)
Inhibition of fibrinolytic system (plasminogen activator inhibitor)
There are 3 major glycoprotein receptors that aid in platelet coagulation. Name them and tell me their functions.
- GPIb: (binds vWF)
Initial tethering of platelet - GPVI (binds collagen)
- - Adhesion and Initial activation of platelet
- - Release of platelet activators (ADP, serotonin, and TXA2) - Activated GPIIb/IIIa (binds fibrinogen)
- - Most abundant receptor on surface of platelets
- - Facilitates platelet-platelet interactions
- - GpIIb/IIIa inhibitors used to inhibit platelet aggregation that occurs during myocardial infarction
Give me an overview of blood coagulation, illustrating 3 key points including the types of clots made, what they’re made of, and how
Coagulation system forms insoluble fibrin clots that are much more secure than platelet plugs
Clot is composed of meshwork of crosslinked fibrin fibers that trap blood cells and serum
Fibrin is made when fibrinogen (a plasma protein produced by the liver) is converted to fibrin by a protease called thrombin
What is thrombin? what does it do and what role does it play in the coagulation cascade?
Thrombin is a protease that cleaves fibrinogen forming fibrin monomers - it is the central protease of the coagulation cascade
Soluble fibrin monomers spontaneously form fibrin fibers
Thrombin activates Factor XIII
Factor XIIIa induces fibrin fibers to cross-link forming a stable insoluble blood clot
How is thrombin formed through the coagulation cascade? (4) Describe the process in generalized terms
The prothrombin activator complex activates prothrombin into thrombin (the active protease)
Prothrombin activator complex is formed by complex reaction cascade involving the coagulation factors
Enzymatic cascade starts when a precursor (inactivated coagulation factor) is activated
This active coagulation factor then activates the next coagulation factor in the cascade
List the 12 coagulation factors of the coagulation cascade
- fibrinogen
- prothrombin
- tissue factor
- calcium
- Factor V
- Factor VII
- Factor VIII
- Factor IX
- Factor X
- Factor XI
- Hagemen factor/Factor XII
- Factor XIII
Which coagulation factor is released in its active state from the start?
tissue factor
What type of protein is prothrombin? Where/how often is it produced?
plasma protein - continuously produced by the liver
Tell me the overall function of the extrinsic pathway of coagulation, as well as what the end result is (6)
Extrinsic pathway activated when damages exposes tissue factor from traumatized tissue
Initial activation of extrinsic pathway causes formation of the Tissue factor complex
This activates Factor X into Xa, which slowly forms thrombin
Small amounts of thrombin then activate Factor V (which is secreted from active platelets)
Factor Va forms the Prothrombin activator complex with Factor Xa, increasing speed of thrombin production 1000-fold
Small amount of thrombin can induce a large thrombin production burst
What initiates the extrinsic pathway of coagulation to start?
tissue injury
What factor is affected by hemophilia A?
factor VIII
Give me brief overview of what happens in the intrinsic pathway - tell me what initiates it, what regulates it and what the result is
Intrinsic pathway is initiated when Factor XII is exposed to collagen and is activated
Thrombin feeds back to activate Factor VIII into Factor VIIIa, which forms the tenase complex with Factor IXa
Tenase complex significantly accelerates the formation of Factor Xa
What is the tenase complex?
prothrombin activator complex
Made of active factor IX, active factor VIII, Ca, and phospholipids
Where do the intrinsic and extrinsic pathways of coagulation converge?
factor X
How does warfarin work?
Warfarin reduces vitamin K levels and decreases coagulation by causing problems for the factors that use vitamin K (factors 2, 7, 9, 10)
It inhibits the reductase enzyme used to permit the vitamin K to activate these factors
Which 4 coagulation factors require vitamin K to work? How does this happen?
Factors II, VII, IX, X
A reduced form of vitamin K is used as a cofactor in the carboxylation of key glutamate residues in these factors
Allows Ca2+ to bind, which facilitates activation of these factors
What is aPTT? Which pathway does it get used on?
Hi We - PTT is for the intrinsic pathway (heparin regulated)
Mix blood with phospholipids, and a negatively charged surface like glass beads, which initiates the intrinsic pathway
Measure time for coagulation
What is PT? Which pathway does it use? How do we measure the results?
Used on extrinsic pathway (Regulated by warfarin)
Mix blood with thromboplastin (composed of tissue factor and phospholipids) and calcium
Results are given as the international normalized ratio (INR)
INR is calculated by first normalizing patient’s PT to mean normal PT
This ratio is then raised to a power designated international sensitivity index (ISI), which is a function of the specific thromboplastin reagent being used
What is the purpose of the anti-coagulation system?
Reduces coagulation system activity to prevent it from running out of control at injury site and by preventing clotting in undamaged vasculature
What are the 2 mechanisms of the anti-coagulation system?
Preventing thrombin formation by inhibiting coagulation factors upstream of thrombin
Inhibiting thrombin that is already formed
How does thrombin work in an anti-coagulant manner? (hint: it binds to another molecule)
Thrombin can decrease further production of itself by interacting with thrombomodulin
Thrombomodulin is located on endothelial cells
Binding of thrombin to thrombomodulin activates protein C
Activated Protein C (APC)/protein S complex is a serine protease that degrades Factor Va and Factor VIIIa
What is factor V Leiden thrombophilia?
Mutation in Factor V prevents it from being inactivated by APC
Leads to an hypercoagulable state
What does heparin do to anti-thrombin activity?
speeds it up
Outline the role of heparin in the anti-coagulation system
Heparin or heparin sulfate binding to antithrombin speeds thrombin proteolysis by at least a 1000-fold
Heparin has no direct anticoagulation effect by itself
Activated platelets negative regulate anticoagulant system by releasing heparin neutralizing factor
What is anti-thrombin (III)? What does it do?
Antithrombin (also called antithrombin III) is a circulating plasma protease produced by the liver and is present in blood plasma
Breaks down thrombin and inactivates numerous coagulation factors (X, IX, XI, XII)
What is tissue pathway factor inhibitor (TFPT) and what does it do?
Tissue factor pathway inhibitor (TFPI) is secreted by vasculature endothelial cells into the blood
TFPI reduces thrombin formation by inhibiting the Factor VIIa/Tissue factor complex and Factor Xa
another point where the vascular system interacts with the coagulative system
What are the 2 things our fibrinolytic system is responsible for?
Degradation of fibrin clots after an injury is healed
Degradation of fibrin clots that form at inappropriate sites
What are the 2 negative regulators of the fibrinolytic system?
plasminogen activator inhibitor (PAI)
alpha 2 plasmin inhibitor
Plasminogen activator inhibitor - what is it and what does it do?
Released by platelets, endothelial cells (inhibits t-PA activity) = prothrombolytic
Negatively regulates the fibrinolytic system
Alpha 2 plasmin inhibitor - what is it and what does it do?
Synthesized by liver and present in plasma at relatively high concentrations
Negative regulation of fibrinolytic system
Outline the functioning of the fibrinolytic system and tell me how plasmin is involved (4)
Plasmin is created by the proteolytic cleavage of plasminogen by tissue plasminogen activator (tPA)
Plasminogen is a plasma protein synthesized by liver
tPA is synthesized by vasculature endothelial cells
Recombinant tPA is used to treat thrombotic stroke and myocardial infarction
CCK - where it comes from, what its 4 targets are and what it does at each target
comes from the duodenum
- Pancreas – increases enzyme secretion
- Gallbladder – increases contraction
- Stomach – decreases empyting
- Sphincter of Oddi – increases relaxation
Gastrin - where it comes from, what its 3 targets are and what it does at all three
from G cells of stomach
promotes gastric acid secretion at parietal cells, ECL, D cells
Motilin - where it comes from, what its 2 targets are and what it does at both
from upper GI
increases smooth muscle contraction at stomach and duodenum
Peptide YY - where it comes from, what its 2 targets are and what it does at both
from ileum and colon
decreases enzyme and fluid secretion from pancreas
Secretin - where it comes from, what its 2 targets are and what it does at them
comes from duodenum
- pancreas - increases bicarb secretion
- stomach - decreases acid secretion, delays gastric emptying
Somatostatin (hormonal) - where it comes from, what its 4 targets are, and what it does at each
from stomach, duodenum, and pancreatic cells
- stomach - decreases acid secretion
- intestine - increases fluid absorption, decreases smooth muscle contraction
- pancreas - decreases secretions
- liver - decreases bile flow
Prostaglandins - where they come from (2), what their 2 targets are and what they do at each (3/2)
come from stomach to act on stomach by increasing blood flow, decreasing acid secretion and increasing mucus/bicarb secretion
come from intestine/immune cells to act on intestine by increasing motility, increasing fluid secretion
3 substances/factors that act in a paracrine fashion to regulate the GI
prostaglandins, histamine, somatostatin
6 major hormonal regulators of the gI tract
somatostatin, CCK, peptide YY, secretin, motilin, gastrin
Histamine - 2 major sources, 2 major targets, 2 major actions in the GI
from stomach, acts on stomach to increase acid secretion
from intestine/immune cells to act on intestine to increase fluid secretion
Somatostatin (paracrine) - 3 sources, 2 targets, and the actions at each
from stomach, acts on stomach to decrease acid secretion and increase fluid absorption
from duodenum and pancreatic cells, acts on intestine to decrease smooth muscle contraction
What is Dypshasia? There are 2 kinds. Tell me some common causes of each.
Difficulty swallowing; can be due to mechanical or functional impairments
- Mechanical impairments: tumors, strictures, herniations, reflex disease, alcohol/tobacco use
- Functional impairments: disruption of striated muscle or neuronal disorder like achalasia (result of denervation of esophageal smooth muscle and impaired function of LES) or Parkinson’s
What are hiatal hernias? Differentiate between the two kinds and tell me which causes each.
Diaphragmatic hernias which are caused by protrusion of the stomach through the diaphragm and into the thorax
- Most are sliding type. In the sliding type, the stomach slides into the thoracic cavity through the esophageal hiatus. Causes: coughing, bending, obesity, ascites, pregnancy.
- A second type is paraesophageal hiatal hernia – here the greater curvature of the stomach protrudes through an opening or tear in the diaphragm. Often occurs with reflux, ulcers, pancreatitis, etc.
Patients should avoid flat supine position and exercises with increased intra-abdominal pressure.
cystic fibrosis
leads to impaired salivary secretions through loss of CFTR protein that causes ducts to clog which results to damage to ducts and surrounding tissue; the surrounding tissue is replaced by fibrotic and fatty tissues; affects lungs, sweat glands, liver, etc.
Sjogren’s syndrome and its effects on the oral cavity
loss of CFTR; autoimmune disease of salivary glands; results in having a dry mouth
Tell me the 4 phases of gastric acid secretions and describe the stimuli that causes them
- interdigestive
- cephalic - activated by stimuli such as the sight or smell of food - These stimuli trigger a vagal response resulting in acid secretion
- gastric - vagal stimulation mediates secretion during the gastric phase - However, the stimulus is derived from distension of the stomach. Additionally, protein products in the stomach further induce acid secretion
- intestinal - The peptides induce the release of gastrin to increase activity of the parietal cell. The parietal cells may also be regulated by amino acids absorbed in the duodenum.
Clinical importance of Zollinger-Ellison syndrome
causes high serum gastrin levels; leads to development of acid-peptic disease
Three phases of pancreatic secretion and what regulates them
Cephalic – stimulated by sight, sell, taste, mastication – regulated via vagal pathways – 25% of max enzyme secretion
Gastric – stimulated by distension, gastrin, peptides/peptones – regulated by vagal/gastrin pathways – 10 to 20% of max enzyme secretion
Intestinal – stimulated by amino acids, fatty acids, H+ - regulated by CCK, secretin, enteropancreatic reflexes – 50 to 80% of max enzyme secretion
Stimulus(i) for returning the levels of pancreatic secretion from fed state to interdigestive state
Once the contents of the intestines, primarily fats, reach the ileum there is a release of peptide YY and somatostatin which decreases pancreatic secretions and returns activity to the interdigestive state.
What is cholecystitis?
Inflammation of the gallbladder. The inflammation can be caused by a stone becoming lodged in the cystic duct
What is cholelithiasis?
The formation of gallstones in the gallbladder. These stones are of two types: cholesterol or pigmented
What is cirrhosis?
Is characterized by fibrosis (scarring) of hepatic tissue resulting in altered hepatic blood flow and function. The scarring of the hepatic tissue is a result of inflammatory process stemming from hepatitis (acute or chronic), alcoholism, biliary obstructions, or autoimmune conditions.
Symptoms of a cirrhotic liver include portal hypertension and hepatocellular changes such as jaundice.
Categorization of cirrhosis include: alcoholic, biliary.
What is jaundice?
condition of hepatocellular failure that is characterized by a yellowing of the skin due to elevated blood levels of bilirubin.
Irritable bowel syndrome
Irritable bowel syndrome is an idiopathic chronic relapsing disorder characterized by abdominal discomfort (pain, bloating, distension, or cramps) in association with alterations in bowel habits (diarrhea, constipation, or both).”
Inflammatory bowel syndrome
Can be divided into two distinct diseases, ulcerative colitis and Crohn’s disease. Both diseases are characterized by inflammation of the GI tract.
Hirschsprung’s disease
functional motility disorder of the colon; This disease is a congenital disorder that occurs during development and is associated with the loss of ganglionic cells from the submucosal plexus and myenteric plexus that control the distal colon. The result is constipation, megacolon, and narrowing of a segment of the colon
Identify the sites of absorption for water soluble vitamins and minerals (folic acid, vitamin B12, calcium, and iron**).
folic acid - duodenum via exchange protein on surface of enterocytes
vitamin B12 - ileum via IF binding
calcium - duodenum via calcium channels in enterocytes
iron - small intestine
