Exam # 2 Flashcards
1
Q
Which segment of the small intestine or proximal large intestines has the highest permeability through its tight junctions?
A
Jejunum
2
Q
Which segment of the small intestine or proximal large intestines has the lowest permeability through its tight junctions?
A
Colon
3
Q
Which segment of the small intestine or proximal large intestines has the highest resistance through its tight junctions?
A
colon
4
Q
Which segment of the small intestine or proximal large intestines has the lowest resistance through its tight junctions?
A
Jejunum
5
Q
Where does the water absorption take place in the gastrointestinal tract?
A
85% of water absorption intestine
takes place in the small intestine (55% in duodenum
and jejunum and 30% in ileum); about 14% is absorbed in the large
intestine
6
Q
What is required for efficient absorption of water?
A
- Increasing resorption surface
- Mucosa uptake mechanisms
- High blood perfusion
- Permeability
7
Q
How are the monovalent ions absorbed?
A
Na+ transport is very efficient since it represents the driving force for most transport processes Chloride is absorbed by carriers as well as passice through the paracellular pathway K+ is mainly absorbed in the small intestine through the paracellular pathway
8
Q
List in order of lowest to highest permeability the sections of intestine.
A
Colon -> Ileum -> Jejunum
9
Q
List in order of lowest to highest resistance the sections of the intestines.
A
Jejunum-> Ileum -> Colon
10
Q
What does calcitriol do?
A
Increases apical Ca++ channels Increases calbindin synthesis Increase Ca++ ATPase
11
Q
Where is Mg++ absorbed?
A
Through Mg++ channels and paracellularly
12
Q
How is Phosphate absorbed?
A
Through Na+/Phosphate symporter.
13
Q
Where is viatmin D produced? What influences its synthesis?
A
Produced in the kidneys. Synthesis is under the influence of PTH
14
Q
What is calcium absorption modulated by?
A
Modulated by vitamin D in intestine
15
Q
What is calcitriol and what will it stimulate?
A
Calcitriol is active vitamin D hormone. It will stimulate building/ opening of calcium channels at apical membrane.
16
Q
What occurs to the diameter of the intestine as we move from oral to aboral?
A
Diameter decreases as we move through GI tract.
17
Q
What is haptocorrin and what does it do?
A
Transcobalamin I. This protects B12 from stomach acid.
18
Q
What releases B12 from Haptocorrin?
A
Trypsin
19
Q
Where is B12 absorbed?
A
Ileum
20
Q
Where is iron absorbed ?
A
Small intestines
21
Q
What breaks down Fe3+ to Fe2+?
A
Ferriductase
22
Q
What is iron important for ?
A
The development of RBC/ B12
23
Q
Why is iron oxidized?
A
So it could be bound to protien (apotransferrin) which is converted to transferrin.
24
Q
What are the energy poor end products of catabolites?
A
CO2, H2O, NH3
25
What are the precursor molecules of complex molecules that are anabolites?
Some amino acids, Sugars, fatty acids, nitrogenous bases.
26
What are some energy sources in living organisms?
Glucose, Fatty acids, amino acids, ketone bodies, volatile fatty acids.
27
What are the phases of energy metabolism?
- absorptive phase: during active digestion and absorption of nutritents from the gut.
- Post absorptive phase: between meals, nutrients are being mobilixed from storage pools to tissues.
- Prolonged energy deficiency or food deprivation
28
What occurs during the absorptive phase of energy metabolism?
- Insulin is released
◦ Glucose is taken up by the liver and converted to glycogen and fatty acids o Fatty acids are sent out of the liver in VLDL to adipose tissue or muscle
◦ Amino acids are used for protein synthesis or are deaminated for gluconeogenesis
29
What is gluconeogenesis? Glycongenolysis?
Gluconeogenesis: Formation of new glucose
Glycogenolysis: Reuse of glucose.
30
What occurs during the post absorptive stage of energy metabolism?
◦ Glucagon is released (by liver)
◦ Glycogenolysis and gluconeogenesis are stimulated.
◦ Amino acids are mobilized from muscle.
31
What is occuring during a period of prolonged energy deficiency or food deprevation?
◦ Glucose and amino acids are conserved
◦ Fatty acids are mobilized in the form of non-esterified fatty acids (NEFAs)
◦ Formation of ketone bodies in the liver (mitochondria)
32
What happens in terms of carbohydrate utilization in glycolysis?
• Glycolysis: Once in the portal blood, glucose will reach the liver Glucose transport into cells is mediated by GLUT
33
How many GLUT transporters are there, and are they very specific?
• \> 14 different GLUTs (highly tissue-specific, insulin-induced)
34
What is glycolysis?
* Glycolysis is central ATP producing pathway as it produces energy without O2.
* Red blood cells and muscle take advantage of anaerobic glycolysis.
35
What is the net gain with glycolysis?
• Net gain:
◦ 2 pyruvate + 2 NADH + 2 ATP
36
What happens to the pyruvate after glycolysis?
It is converted into lactate.
◦ Pyruvate -\> mitochondria
◦ NADH -\> electron transport chain -\> NAD+
37
Why is NAD+ important?
NAD+ is needed to make more pyruvate.
38
What can be formed/ found after chronic inappetence?
increased ketone bodies
39
What can cause metabolic acidosis?
Increased lactate.
40
What is Aerobic glycolysis?
• Aerobic glycolysis: direct consumption and formation of ATP is the same as in anaerobic glycolysis, also NADH production is the same but pyruvate is imported into the mitochondria (to produce ACoA that enters into the Krebs cycle) and NADH can be oxidized (regeneration of NAD+) during the electron transport chain. During electron transport chain, 3 ATPs are produced for each NADH molecule that has been oxidized
41
What is anerobic glycolysis?
• Anaerobic glycolysis: 2 ATPs are generated for each molecule of glucose converted to 2 molecules of lactate (no net production of NADH)
42
What is the TCA cycle?
• The Tricarboxylic Acid Cycle (TCA)
◦ The TCA aka Krebs cycle or citric acid cycle is the final pathway where carbohydrates, amino acids, and fatty acids converge
‣ TCA is a traffic circle („roundabout“)
◦ The energy provided by the TCA is essential for most animals and humans
◦ TCA occurs close to the electron transport chain
◦ The process is aerobic because oxygen is used as an electron acceptor
◦ It delivers reduced NADH and FADH2
43
What is gluconeogenesis?
• Gluconeogenesis: Production of glucose from non-sugar molecules such as amino acids, lactate, and glycerol
44
What can occur during a prolonged fast?
• During a prolonged fast, hepatic glycogen stores are depleted, glucose is then formed from precursors other than carbohydrates (i.e. lactate, pyruvate, glycerol from TAG, and alpha-ketoacids from amino acids)
◦ Important tissues for gluconeogenesis: Liver and kidney
◦ Gluconeogenesis. Important substrates:
‣ Glycerol -\> Glycerol Phosphate
‣ Lactate -\> Pyruvate
‣ Amino acids -\> TCA Cycle -\> Oxaloacetate
45
What is glycogenesis?
* Glycogenesis is a mechanism to store glucose as glycogen in order to mobilize glucose in absence of a dietary source Main stores in the body: skeletal muscle and the liver
* Glycogenolysis is the process by which glucose is mobilized from glycogen granules in order to be sent into the blood and to other tissues
46
Where does the pentose phosphate cycle occur and what is another name for it?
• The pentose phosphate cycle - occurs in the cytosol (aka "hexose pathway")
47
What are the functions fo NADPH in physiologic channels?
An important source of electrons (reductases in the body)
• Carrying electrons to the electron transport chain complexes
• Reducing the enzyme cytochrome P450 (steroid hormone synthesis, bile acid synthesis, detoxyfication, etc)
• Respiratory burst in phagocytic cells (NADPH oxidase produces reactive oxygen species to kill bacteria)
• Synthesis of NO
48
What are the fate of dietarty lipids in the body?
Fate of dietary lipids in the body—very simplified Short- and medium-chain fatty acids: -\> get into the portal circulation (bound to albumin) and reach, finally, the liver
• Chylomicrons: -\> TAGs will be converted into free fatty acids and glycerol by the enzyme lipoprotein lipase which is expressed at the capillaries of skeletal muscle, adipose tissue, heart, lung, kidney, liver. FFA can be stored as TAG (adipocytes) or can be used to produce energy (in other cells) or remain in the blood (bound to plasma proteins)
• Chylomicron remnants (i.e. cholesteryl ester, phospholipids, lipoproteins, fat-soluble vitamins) will be endocytosed (receptor-mediated) by liver cells
49
What is the relevance of fatty acids?
◦ Energy: during a fast period fatty acids are bound to albumin in plasma (free fatty acids) on the way to the tissues (coming from adipose tissue) -\> oxidation (energy production in most tissues)
◦ Structural components: phospholipids and glycolipids in the plasma membrane
◦ Hormone precursors: prostaglandins
◦ Energy reserve: TAG in adipose tissues
50
What is the net gain of B-oxidation of fatty acids?
◦ From 1 palmitoyl CoA that has been oxidized to CO2 and H2O -\> 8 ACoA, 7 NADH, 7 FADH2
◦ From these molecules 131 ATP can be generated (minus 2 ATP needed = 129 ATP!)
51
What occurs in ketone body formation?
◦ The liver (mitochondria) can convert ACoA from fatty acid oxidation into ketone bodies –acetoacetate, 3-hydroxybutyrate (ß-) and acetone—which are important sources of energy during fast periods
◦ During a prolonged fast, fatty acids mobilized from adipose tissue come to the liver yielding much more ACoA than necessary (also fatty acid oxidation produces high amounts of NADH which shifts OAA to malate). The result is the utilization of excess ACoA for ketone bodies formation In peripheral tissues, ketone bodies are converted into ACoA which enters the TCA cycle
52
What are the Peptides and Polypeptides of physiologic importance?
• Peptides of physiological relevance:
◦ Oxytocin: produced in the hypothalamus (uterine contractions and milk
• secretion)
◦ Antidiuretic hormone (ADH): produced in the hypothalamus and essential for maintenance of water balance
◦ Bradykinin, a vasoactive substance
◦ Angiotensin II, a potent vasoconstrictor
• Polypeptides with physiologic relevance:
◦ Gastrin, stomach hormone, stimulates secretion of gastric glands
◦ CCK, stimulates pancreas and liver secretion
◦ Glucagon, produced by alfa-cells of the pancreas
◦ Atrial Natriuretic Peptide (ANP): produced in the heart (atria), essential for regulation of blood volume and pressure
53
What are the branch chain amino acids and what do they do in muscle cells?
* Branch-Chain amino acids (BCAA) serve as source of energy in muscle cells Valine, Leucine, Isoleucine After deamination, BCAA are converted into α-ketoacids which enter the TCA. At the same time pyruvate serves as an acceptor of the BCAA‘s amino group yielding to the formation of the amino acid alanine which leaves the muscle and is used by the liver for gluconeogenesis
* Alanine from branch-chain amino acids (BCAA) metabolism represents an important way to eliminate ammonia (NH3) from the body through the formation of urea which occurs only in the liver
54
What is the extrinsic control of GI tract?
Vagus and splanach nerves, non gi hormones, calcitriol
55
What is the intrinsic control of the gi tract?
Located in the wall of the GI tract (enteric nervous system of gi tract)
56
Does the GI tract function with the brain?
No the GI tract functions without the brain. The gut can keep moving outside of the body if provided adequate conditions
57
What plexus is located between the submucosa and circular muscles? What is its function?
Messiners Plexus, or plexus submucosa
Regulates mucus secretion and food absorption.
58
What plexus is located in the muscularis externa between the longitudinal and circular muscles? What is its function?
Plexus Myentericus ( Auerbach)
Control of the muscular activity (tone and contractions rhythm)
59
What are the cells of the GI tract arranged in and how many fibers are found?
* Cells are arranged in bundles of as many as 1000 parallel fibers (longitudinal or circular arranged)
* Within each bundle, muscle fibers are electrically connected with one other through gap junctions
* Each bundle of smooth muscle fibers is partially separated from the next by loose connective tissue, but the muscle bundles fuse with one another at many points and work as a syncytium (from Greek syn = “together“ and kytos = “cell“)
60
What are the functions of Senory nerve cells?
Detect changes/ stimuli and regulate function
61
What are mechansensitive cells?
recognize stretching of intestinal wall or volume changes (intraluminal pressure) and induce a response (e.g. gastric phase of gastric acid secretion)
62
What are chemosensitive cells?
(chemoreceptors): detect the presence of nutrients in the GI lumen, changes in the osmolarity, and changes in the pH and induce a response (e.g. sensibilization of enteroendocrine cells)
63
What is the function of interneurons?
• Interneurons: Process signals coming from other nerve cells or from the CNS and propagate them to other neurons (motor neurons)
64
What are motor neurons? What are the three types and their locations?
Induce change in the GI tract in response to a stimulus.
◦ Muscle motor neurons: primary located in the plexus myentericus
◦ Secreto motor neurons: primary located in plexus submucosus
◦ Vaso motor neurons: in both plexuses
65
What regulates GI function?
• Types of neurotransmitters secreted by enteric neurons
66
What are examples of the Non adrenerfic non cholinergic NANC substances?
```
Nitric oxide (NO); inhibitory substance that reduces the motility of the GI tract
‣ VIP (vasoactive intestinal polypeptide); inhibits gastric secretion, and causes vasodilation and relaxation of smooth muscle sphincters
‣ Substance P; excitatory substance, increases secretion and motility of the GI trac
```
67
What does the parasympathetic nervous system use to stimulate many GI functions?
Acetylcholine
68
What do preganglionic fibers of the PNS become integrated with?
fibers of the ENS.
69
What are the postganglionic neurotransmitters of the ENS?
‣ Acetylcholine (excitatory)
‣ NANC Substances VIP and NO (inhibitory)
70
What does the sympathetic nervous system use on the GI tract and what is its effect?
• Sympathetic nervous system uses Noradrenaline which has an inhibitory effect on the GI tract.
71
What has an origin in the medulla oblongota through the vagus nerve?
• Oesophagus, stomach, small intestine, colon, ascenders, pancreas, gallbladder, and liver
72
What has an origin in the sacral spinal cord through the pelvic nerve?
Colon descend and distal part of GI tract
73
What is the sympathetic ganglion chain and where are they located?
• On either side of the spinal cord, many sympathetic ganglia are arranged like a string, forming the sympathetic ganglion chain
74
What is the length of preganglionic and postganglionic neurons? ( are they short or long?)
• Preganglionic neurons have short axons, whereas postganglionic neurons have long axons extending to the target organs
75
What is the postganglionar neurotransmitter?
• Noradrenaline (inhibitory)
76
What are the two types of electrical waves of the electrical activity of the GI smooth muscle cells?
◦ The smooth muscle of the GI tract is excited by almost continual, slow, intrinsic electrical activity along the membranes of the muscle fibers.
◦ Two basic types of electrical waves:
‣ Slow waves
‣ Spikes.
77
What will change the speed and strength of peristalisis?
Peristalisis is always there but neuro component changes speed/ strength of peristalisis
78
What do slow waves indicate?
Most GI tract contractions occur rhytmically, this rhythm is determined mainly by the frequency of the “slow waves“ in smooth muscle membrane potential Slow waves are not action potentials; they are slow, ondulating changes in the resting membrane potential Intensity about 5 – 15 mV
Slow waves -\> no contractions.
79
What is the frequency of slow waves?
3 – 12 per minute (3 in the stomach, 12 in the duodenum, 8 to 9 in the terminal ileum
80
What are ICC?
specialized smooth muscle cells, the interstitial cells of Cajal (ICC)
81
What originates from ICC?
Slow waves
82
What are the functions of ICC?
◦ ICC are believed to be electrical pacemakers for smooth muscle cells ( similar to purkinje cells in the heart)
◦ ICC form network with each other and are interposed between the smooth muscle cells.
◦ ICC under cyclic changes and membrane Potential due to unique ion channels that periodically open and produce currents.
83
What are spike potentials?
These are true action potentials Occur automatically when the resting membrane potential of the GI smooth muscle becomes more positive than about -40 mV
84
What will cause induction of action potentials from slow waves?
◦ Slow waves will only induce an action potential when they reach smooth muscle cells that are (or were previously) sensitized
◦ Each time the peaks of the slow wave become more positive than -40 mV -\> spikes potentials appear on these peaks
◦ The higher the slow wave potential rises, the greater the frequency of the spike potentials
85
What are the 3 reflexes essential to GI function?
1) Reflexes that are integrated entirely within the gut wall: control of GI secretion, peristalsis, formation of mixing contractions, local inhibitory effects, etc
2) Reflexes from the gut to the pre-vertebral sympathetic ganglia and then back to the GI tract: transmit signals long distances to other areas of the GI tract
3)Reflexes from the gut to the spinal cord or brainstem and then back to the GI tract
86
What are the 3 reflexes from the gut to the prevertebral sympathetic ganglia and then back to the GI tract?
◦ gastrocolic reflex: signals from the stomach that causes evacuation of the colon
◦ enterogastric reflex: signals from the colon and small intestine inhibit stomach motility and stomach secretion
◦ colonoileal reflex: signals from the colon that inhibit emptying of ileal contents into the colon
87
What are examples of Reflexes from the gut to the spinal cord or brainstem and then back to the GI tract ?
◦ Reflexes from the stomach and duodenum to the brainstem and then back to the stomach to control gastric motor and secretory activity
◦ Pain reflexes that cause general inhibition of the entire GI tract
◦ The defecation reflex which travels from the colon and rectum to the spinal cord and back again to produce the colonic, rectal, and abdominal contractions required for defecation
88
What is the peristaltic reflex?
Stretching of the intestinal wall during the passage of a bolus triggers a reflex that constricts the lumen behind the bolus and dilates the lumen ahead of it -\> coordination of longitudinal and circular musculature -\> propulsive movement of the chyme.
89
What direction does the bolus of chyme travel in the SI?
Oral to aboral
90
What muscles move proximal to the site of distension during peristalisis?
Proximal to the site of distention -\> longitudinal muscle relaxes, circular muscle contracts
91
What muscles move distal to the site of distention during peristalisis?
longitudinal muscle contracts, circular muscle relaxes
92
What do excitatory neurons release during peristalisis?
• Excitatory motor neurons release Ach and Substance P -\> smooth muscle contraction
93
What do inhibitory neurons release during peristalisis?
• Inhibitory motor neurons release NO, ATP, VIP -\> smooth muscle relaxation
94
What is the vasovagal reflez?
• The term vagovagal reflex refers to gastrointestinal tract reflex circuits where afferent and efferent fibers of the vagus nerve coordinate responses to gut stimuli via the dorsal vagal complex in the brain
95
What stimulates the vagus affeent fibers? What does it control?
* The stimulation of the mechanical receptors located in the gastric mucosa stimulates the vagus afferent fibers
* It controls motility of the gastrointestinal muscle layers in response to distension of the GI tract by the chime, e.g. receptive relaxation of the stomach in response to mastication of food and deglutition
96
What are the divisions of the monogastric stomach and what is its job?
Proximal region ( extension past fundus) is the fastric reservoir, it stores and retains frood as it awaits eventual entry into the small intestine.
Distal region( area of the corpus) is the gastric pump. It grinds and sieves pieces of food into small particles that can be digested by the small intestines.
97
What is the sequence that causes inflow into the gastric pump
1. ) Gastric reservoir ( Tonic relaxation and contraction)
2. ) Small peristaltic wave in corpus
3. ) Move content into distal ( for mixing / grinding into smaller particles) if particles are not small enough they will go back for another grinding.
4. ) Emptying of fluid/ predigested particles into the duodenum ( fluid empty faster than solids) the finest particles go to duodenum.
98
What occurs during a hypocaloric meal ? Hypercaloric?
Hypocaloric: Stomach empties fast, every contraction of gastric pump will lead to emptying of the pyloric antrum
Hypercaloric: Food will be retained in the proximal part of stomach, food needs more time to mix, and empties slower. Retropulsion is present.
99
What induces the receptive relaxation (vasovagal reflexes)?
Induced by mastication/ degredation of food which activates mechanoreceptors in pharynx.This triggere vagus center, which causes inhibitory vagus nerve fibers ( which use NAC) which leads to short term relaxation of stomach during food intake.
100
What induces the Adaptive relaxation (gastr-gastric reflex)?
Food arrives which causes stressing and some fibers are inhibited.
101
What induces the feed back relaxation reflex ?
When nutrients are reaching duodenum and CCK is released, this induces relaxation due to vagus center. CCK will stop this.
102
What are the functions of intestinal motility?
◦ Mixing food with digestive juices (GI secretions)
◦ Enhancing contact between intestinal wall and food
◦ Peristalsis, the propulsive movement of the chyme to the distal (aboral) direction
103
What are the contraction patterns of the small intestine?
- Propulsive pattern and non propulsive pattern
104
What is the propulsive pattern?
peristaltic waves -\> fast aboral migrating contractions (faster in duodenum, medium in the jejunum and very slow in the ileum)
Speed will decrease as you move along GI tract
105
What is the non propulsive pattern of peristalsis?
Non-propulsive pattern: segmentation contractions -\> localized contractions of circular muscle, small segments of the intestine contract tightly dividing the gut into two segments of constricted and dilated lumen
| (It doesn‘t contribute significantly to the net aboral propulsion of the ingesta but it is important when nutrient concentration is high!)
106
What is another word for non propulsive pattern?
Segmentation
107
What is the duration of contractions of the interdigestive period?
Time in which stomach and small intestine are empty between meals -\> it lasts typically 80-120 min
108
What is Migrating Motoric Complex (MMC) and what does it do?
‣ Helps pushing undigested material out of the intestine
‣ Control of the bacterial population
CLEANS
109
What are the 3 phases of MMC? What is the duration of each stage?
◦ Phase I: motoric rest, no contractions (GI all quiet, ca. 60-70 min)
◦ Phase II: intermittent and irregular contractions sometimes isolated stronger ones (20-30 min)
◦ Phase III: strong peristaltic contractions starting from the stomach and migrating distally to reach the colon (3-10 min)
110
How often does phase 3 of MMC occur?
Occurs every 3 minutes
111
What occurs within the segments of the GI tract during the interdigestive cycle?
Phases will alternate in each segment
112
Which phase begins first in the stomach and duodenum?
Phase III
113
Which phase begins first in the jejunum?
Phase II
114
Which phase begins first in the ileum?
Phase 1
115
What are the motility paterns in the large intestines? What does each pattern do?
• Motility patterns observed in the large intestine are mainly:
◦ Peristaltic waves
◦ Antiperistaltic waves: oral migrating contractions that impede the movement of ingesta, causing a more intense mixing activity
116
TRUE or FALSE: • Mixing activity is prominent in the colon of all species
TRUE
117
What are Haustra?
• In horses and pigs, colonic segmentation is more pronounced and results in the formation of sacculations (=haustra)
118
What are the 2 types of pathologic contractions and what direction do they move?
• Giant contractions: high amplitude and long-lasting contraction
◦ oral migrating -\> vomiting
◦ aboral migrating -\> diarrhea
119
What causes vomiting?
* A defense mechanism and important clinical sign activated in order to eliminate gastrointestinal content
* A complex reflex involving many striated muscle groups and other structures outside the GI tract
* Is coordinated in the brainstem
120
How is stimuli of vomiting classified? What are the classifications?
Stimuli can be classified according to “when/where they originate“:
1) before food intake (color, smell, emotions, appearance of something) 2) after food intake (particles in intestinal lumen) -\> visceral afferents -\> vomiting center
3) after absorption (particles in the blood, e.g. drugs, toxins)
- \> stimulate the chemoreceptor trigger zone (CTZ) in the area postrema
121
What are frequent causes of vomiting?
- Pregnancy
- Medications, Toxins, Pain, Irradiation
- Smell/ Touch
- Cerebral Pressure
- Stomach stretching/ Inflammation
- Rotary Movement
122
What is the sequence of events of vomiting?
1) Antiperistaltic wave originates in duodenum ( vomiting may contain ingesta of intestinal origin)
2. ) Propulsion of ingesta towards stomach
3) Contraction of the abdominal muscles increasing intraabdominal pressure
4) Expansion of chest cavity while the glottis remains closed in order to lower the intrathoracic pressure.
5) Relaxation of LES
6) Opening of UES
123
What are key indications of vomiting? How can you tell it apart from regurgitation?
Vomiting is not normally one retching episode, and can include nausea, dizziness, ect. Abdominal effort is seen with vomiting. With regurgitation you do not see any signs, and there is a lack of abdominal contraction. It can be a single episode.
124
What is diarrhea?
* Diarrhea refers to an increase in frequency of defecation or fecal volume
* This increase is often due to increased water content
125
What is the cause of excess water in the gut?
1) Ingested water
2) Water secreted by glands of the GI tract
3) Water secreted or lost directly through the mucosal epithelium
• Through absorption in the intestine, the amount of secreted water slightly exceeds the amount ingested
• Diarrhea occurs when there is a mismatch between secretion and absorption
126
What are the two types of diarrhea?
- Malabsorptive diarrhea and hypersecretory diarrhea
127
What is malabsorption diarrhea? what can cause it?
• Malabsorptive diarrhea: occurs when absorption is inadequate to recover all secreted water
◦ Viral, bacterial, protozoan infections
◦ Destruction of the villi and reduced length (the rate of cell loss is higher than the rate of replacement)
◦ Shortened villi cause a loss of absorptive intestinal surface area
◦ More affected are mature enterocytes that possess the enzymes of the brush border and transport proteins.
128
What is secretory diarrhea and what can it cause?
• Secretory diarrhea: occurs when rate of intestinal secretion increases and overwhelms the absorptive capacity
◦ Some pathogenic bacteria produce enterotoxins which bind to enterocytes and stimulate the adenylyl cyclase activity and the production of cAMP -\> opening of chloride channels (water and other electrolytes follow)
129
What is the defecation reflex?
* Internal sphincter (smooth muscle) and external sphincter (striated muscle)
* Internal sphincter is both parasympathetic (sacral spinal segment) and sympathetic (lumbar) innervated. In most species, sympathetic stimulation causes constriction of the sphincter; whereas parasympathetic stimulation causes relaxation of the sphincter
* Internal sphincter is normally tonically contracted (continence) Voluntary constriction of external anal sphincter (trained animals) will block the reflective activation of defecation
130
What is the rectospincteric reflex?
• Feces accumulate in the rectum (reservoir) -\> peristaltic movement of feces into the rectum and relaxation of internal anal sphincter -\> urge to defecate (contraction of colon descendens and rectum as well as increase of intraabdominal pressure)
131
What is fermentive digestion?
Fermentative digestion occurs in specialized compartments localized before the stomach
(forestomach in ruminants) or after the stomach and small intestine (cecum and colon in
horses)
132
What are the microbes responsible for fermentive digestion?
The microbes responsible for fermentative digestion include bacteria, fungi, and protozoa
133
What is required for fermentation to occur ( conditions wise)?
Fermentation requires appropriate secretions, motility, and temperature conditions in the forestomachs
134
What in ruminant digestion allows for more finely grinded material?
Associated with fermentative digestion are regurgitation and remastication of food in order to provide more finely divided material and thereby a greater surface area for microbial digestion
135
What organ is the reticulum closest to?
the reticulum is close to the heart
136
What side of the body is the rumen most prominent?
The rumen occupies a prominent portion of the viscera on the left side of the animal
137
What kind of epithelium lines the forestomachs?
Squamous epithelium
138
What stomach in ruminants is the true stomach? What side can it be located?
Abomasum is true stomach. Right side
139
What is the largest compartment of the newborn ruminants stomach? How long is the non ruminant period? And what stimulates development of the adult stomach in a calf?
The abomasum is the largest compartment of the newborn‘s stomach
Enlargement of the forestomach occurs rapidly after birth but the rate depends on diet type (solid feeds accelerate development) and contact with adult ruminants (inoculation of microorganisms)
Nonruminant period: Birth to 3 weeks
140
What is the transitional period for calves to develop their normal adult ruminent stomachs?
3-8 weeks transitional period
141
What are the different grouping of ruminal bacterial species ?
(Hint: 11 total)
- Major celluolytic species
- Major Hemicellulolytic species
- Major Pectinolytic species
- Major amylolytic species
- Major ammonia- producing species
- Major lipid- utilizing species
- Major acid utilizing species
- Major proteolitic species
- Major Ureolytic species
- Major methane producing species
- Major sugar utilizing species.
142
What kind of rumen protozoa can be seen?
Systematically
- Flagelates (few species)
- Ciliates (more numerous)
143
What is the ruminal environement? What is the temperature, fluid content, ph, osmolality, and substrate availability?
- Substrate availability: food intake regulated by volume, structure, energy, palatability
- Temperature: about 0.5 to 1 degree Celsius above the body temperature
- Fluids: drink water and saliva
- pH: 5.5 -7 (acid synthesis and acid reabsorption, buffer substances coming from the saliva and rumen epithelium)
- Osmolality: 260 to ~400 mOsm/l
144
What occurs in the ruminal ecosystem?
Protozoa ingest large numbers of bacteria and hold bacterial number in check Protozoa may also play a role on starch and protein digestion -\> they prolong the digestion of these substances (ingest them and protect them from bacterial action
145
What is the example of syntrophy within the ruminants?
The waste products produced by one species serve as substrate for another
Example:
R. albus digests cellulose but cannot digest protein; B. ruminicola digests protein but cannot digest cellulose, then cellulose digestion by R. albus provides hexoses for the energy needs of B. ruminicola, and protein digestion by B. ruminicola provides ammonia and fatty acids for the growth of R. albus
146
What are the ruminal content layers?
A.) Gas Layer
B.) Fiber Mat (intense fermentation)
C.) Intermediate Zone (intense fermentation)
D.) Liquid Zone ( Moderate fermentation)
147
What are the volatile fatty acids and what is their fate?
VFA:
- Propionate - Liver (glycose)
- Acetate Butyrate - All tissues (energy)
- Acetate - Adipose tissue (Fatty acids)
148
What contains the most carbohydrates in the plants?
The cell wall of plants (leaves and stems) has a large portion of carbohydrates which are important for stability and rigidity of the growing plant (structure carbohydrates)
149
why are plant cell walls important substrates for fermentive digestion?
significant nutrient sources of many microorganism species
150
What are 3 carbohydrates in fermentative digestion and how are they metabolized?
Carbohydrates: cellulose, hemicellulose, pectin Cellulose, hemicellulose and pectin will be hydrolyzed by the enzyme cellulase. After hydrolysis, monosaccharides are released from the polysaccharide. These monosaccharides are NOT available for absorption by the animal; they are further metabolized by the microbes
151
What steps are included in the meyerhauf pathway? What does it look like?
Within the microbial cell, glucose enters the glycolytic pathway to produce 2 pyruvate from one glucose molecule (plus 2 NADH and 2 ATPs which is used by the microbes)
Looks like anearobic metabolism in non ruminants
152
What are the steps of digestion of carbs, protiens, and lipids in the ruminant?
1. ) Essentially all dietary proteins and carbohydrates are subjected to fermentative digestion in the forestomachs
2. ) Products are glucose, other monosaccharides, and short chain polysaccharides that are released into the fluid phase
3. ) This glucose and the other sugars do not become available to the host animal; they are absorbed into the cell bodies of microbes
4. ) Within the microbial cell, glucose enters the glycolytic pathway ...
5. )... to produce 2 pyruvate from one glucose molecule (plus 2 NADH and 2 ATPs which is used by the microbes)
6. ) Fermentative digestion is anaerobic and the products are volatile fatty acids (VFA, = short chain fatty acids, SCFA)
153
How many ATPs are produced from Acetate alone?
4
154
How many ATPs are produced from Butyrate?
3
155
How many ATPs are produced from propionate alone?
4
156
How many ATPs are produced from Acetate and propionate?
3
157
Why are protiens particularly vulnerable to fermentation?
Proteins are particularly vulnerable to fermentation because they are made of carbon compounds that can be further reduced to provide energy for anaerobic microbes
158
What do microbes produce that form short chain peptides as end products? Where are they absorbed?
Microbes do produce endopeptidases that form short-chain peptides as end products -\> these peptides are then absorbed into the microbial cell bodies
159
What can be used to form microbial protien? What can occur instead?
Once in the microbial cell, peptides can be used to form microbial protein or can be further degraded for the production of energy (VFA pathway)
160
What do amino acids contribute to?
* synthesis of microbial protein
* synthesis of VFA and ammoni
161
What can also synthesize amino acids?
Amino acids are also synthesized intracellularly from NH3 and VFA
162
What will happen when protiens are destroyed?
Essentially, protiens will be destroyed and used to make VFA, Ammines, and new protiens.
163
What must occur to an amino acid for it to enter the VFA pathway?
Must first be deaminated.
Deamination:
Amino acid -----\> NH3 + Carbon skeleton
164
Branch chain amino acids can can be.....
formed by adding either, valine, leucin, or isoleucine with CO2 and NH3
165
What do ruminants depend on to meet their own needs?
Because almost all dietary protein is fermented in the rumen, the ruminant depends on microbial protein to meet its own needs
166
What options do the ruminants have for protien absorption/ production?
Option 1: Microbes washed out of the rumen -----\> microbial protein reaching the abomasum and small intestine
Option 2: Protein can be produced in the rumen from protein and non-protein sources such as ammonia, nitrates, urea
167
What is urea recycling?
Urea, the nitrogen waste product of protein catabolism, is synthesized in the liver of the ruminant from two sources: (1) Urea coming from deamination of
endogenous amino acids (2) Nitrogen absorbed as ammonia from
the rumen
168
What is the differences in urea excretion in monogastric species vs. ruminants?
In monogastric animals, urea is excreted by the kidneys; in ruminants urea is also excreted into the rumen (through rumen epithelium and saliva). A portion of the urea reaching the rumen can be resynthesized into protein that will contribute to the amino acid needs of the host animal -\> under conditions of low dietary protein, ruminants are efficient conservers of nitrogen
169
What produces the fats and lipids for digestion? What else can be done to increase ration energy density? What is in most cattle diets?
Fats are rare in plants (\< 5% of dry mass); exception are oilseeds Microorganisms produce the necessary enzymes for lipids digestion, such as lipases and phospholipases
Over the last 25 years, the use of supplemental fats and oils in dairy cow rations has become a standard practice in some production systems Fats are supplemented to increase ration energy density
Most of the cattle diet contains polyunsaturated fatty acids (PUFA)
170
What are the fats and lipids found in the feed? Where exactly can they be found?
Triglycerides: Major lipid type found in cereal grains, oilseeds, animal fats, and byproduct feeds. Also present in milk (milk fat)
Glycolipids: Major lipid type found in forages
Phospholipids: Minor component of most feeds. Form the cell membrane of all animal cells, and the surface of milk fat globules. Important in fat digestion in the small intestine of cows
Free fatty acids: Minor component of dairy feeds, but major component of certain fat supplements
171
What will hydrolize fats?
microbial lipases
Example:
Anaerovibrio lipolytica --------\> Triglycerids
Butyrivibrio fibrisolvens -------\> Phospho- and glycolipids
172
What is the results of fats hydrolized by microbial lipases?
Glycerol, sugars, and free fatty acids
Glycerol and sugars -\> VFA
Released fatty acid -\> hydrogenation (biohydrogenation)
173
Where are fatty acids synthesized and where will absorption take place?
Synthesized - rumen
Absorption: abomasum and small intestine
174
What is the typical Acetic/propionic/butyric acid concentration ration in ruminants eating high forage diets and eating high grain diets?
70: 20:10 for animals eating high-forage diets
60: 30:10 for animals eating high-grain diets
175
What vitamins do microbes synthisize in ruminants?
- Vitamin C
- Vitamin K
- Vitamin B:
- B1 (thiamin)
-B12 (cobalamin)
176
What can cause vitamin B1 deficiency, B12?
- B1 (thiamin) deficiency is observed after a sudden change of feed from
roughage to concentrate
- B12 (cobalamin) deficiency in cobalt poor soils or using diets with too much grain
177
What animals cannot synthesize these vitamins and why?
due to the relative small fermentative activity in young ruminants, calves and lambs are not able to synthesize vitamins and these must be supplied with the diet
178
What are common substances in the rumen?
VFA, Na+, Cl-, Mg++, Ca++, H2PO4, HCO3-, Glucose
179
What can happen with a rapid diet change in a ruminant?
Rapid diet change destroys microflora and will decrease B1 synthesis
180
What is the difference between Ionized and Non ionized pathways of absorption of VFAs?
- Non ionized can diffuse through membrane easily
- Ionized carriers need (HCO3-/AC- antiporter)
181
What can happen with a diet that is starch rich?
Fast-fermentable carbohydrates (starch-rich diet) lead to an increase in VFA production -\> pH in the rumen gets more acidic
182
What is the normal pH of the rumen, and what is dependent on the pH of the rumen?
Ionization grade of VFA depends on the pH of the rumen (normal pH 5.5-7)
183
What is a Pk?
(pK indicate the pH at which a substance is 50% ionized and 50% non-ionized)
184
What occurs with the decrease in pH from a starch rich diet?
The acidic pH in the rumen stimulates proliferation of lactate-producing bacteria - \>exacerbation of the acidosis
185
What are the reasons for ruminal acidosis?
- Fast fermentable carbs
- Generation of high amounts of VFA
- Reduced mastication ( low HCO3-)
186
What occur intracellularly during ruminal acidosis?
Intracellular acidosis can occur due to more VFAs being in their non ionized form and being more able to diffuse into the cell.
187
How is sodium absorbed in the rumen?
1) Electrogenic transport: Na+ channel ( This generates gradient),
2) Electroneutral transport: NHE (Na+/H+ exchanger) (Exchanger)
3) Basolateral Na+/K+ ATPase
188
How does chlorine get absorbed into the rumen?
1) Cl-/HCO3- exchanger (antiporter)
2) Basolateral channel (not fully identified)
189
How does potassium get absorbed into the rumen?
1) Apical and basolateral channels
2) High luminal K+ concentration (transepithelial
potential difference)
190
Which side is more positive in terms of potassium, the luminal side or the portal side (blood)?
The portal side is more positive
191
Which part of the cell is more negative? Inside the cell or outside of the cell?
Inside of the cell is more negative
192
How is magnesisum absorbed in the rumen?
1) Electrogenic transport: Mg++ channel (dependent on potential difference between apical/basolat. side)
193
Where can you find areas of high K+ concentrations? What can this lead to in ruminants
Presence of high K+ concentrations are found in young pastures or potassium-fertilized pastures. This can lead to pastures grass tetany.
194
What is pastures grass tetany? What are the clinical signs?
Hyperkalemia from K+ fertilized/ young pastures.
Clinical signs: Irritability, mucscle twitching, staring, incoordination, staggering, collapse, thrashing, head thrown back, and coma, followed by death
195
What is the treatment of pastures grass tetany?
IV Magnesium solution. Can be corrected if not too late.
196
How is calcium absorbed in the rumen?
Reabsorption not fully understood
1) Probably electroneutral (Ca/H exchanger; not fully understood)
2) Basolateral Na/Ca exchanger And Ca ATPase
197
What is the omasum composed of, what does it look like? what do the composition do?
The omasum is composed of muscular folds (or leaves) that project from the greater curvature into the lumen. The canal connects reticulum with the abomasum
Bible folds.
198
What is the functions of the omasum?
- Concentration of the ingesta
- SCFA (VFA) absorption
(diffusion more relevant here)
- Na+ and Cl- absorption
- HCO3- reabsorption
| (absorption of water)
199
What is the role of rumen pillars and reticular folds
Reticular folds and rumen pillars are motile and they elevate and relax accentuating or reducing the divisions within the rumen
200
What are the 2 kinds of motility patterns in the rumen?
* mixing (primary contractions)
* eructation (secondary contractions)
201
What is responsible for the motility of the walls of the forestomach?
The walls of forestomachs are motile too and possess an enteric nervous system which is responsible for the motility patterns
202
What are the steps of the primary contractions in rumen motility?
A. The bolus into rumen (suspended near the cardia)
B. Biphasic (double) contraction of the reticulum
(1) First contraction is weak
(2) Second is forceful nearly obliterating the lumen of the reticulum (bigger particles pushed into the dorsal sac.)
C. Caudal-moving contraction of the dorsal sac moves ingesta further back into the dorsal sac
D. Cranial-moving contraction mixes the ingesta. Ingesta now under bacterial fermentation (producing gas). Gas accumulates in the dorsal sac
E. The smaller particles decant into the ventral sac
F. Contraction of the ventral sac separating big and small material; small goes over the cranial pillar into the cranial sac
G. Contraction of the cranial sac further separates material into big and
small
H. The reticulum contracts, the reticulo-omasal orifice relaxes and small particles (dense material) are forced through the opening into the omasum
A new cycle starts ...
203
What is the function of primary contractions?
The function of primary contractions is to reduce particle size of forage (from 1-2 cm to about 2-3 mm)
204
What has an effect on the rate of particle passage and rate of feed intake?
Digestibility and physical characteristic of feed.
Poorly digestible fiber needs longer to be broken down compared to good quality ones
205
How many reticulo-rumen contractions occur per minute? When are they more frequent? When are they less frequent?
1-3.
More frequent during eating and dissapear during sleep.
206
What determines the rate and strength of ruminal contractions?
Rate and strength of the contractions depend on the structure of the diet
207
What feed will stimulate the most frequent and strongest contractions?
Coarse, fibrous feeds stimulate the most frequent and strongest contractions
208
What is the functions of secondary contractions? When do they occur?
Function is to force gas toward the cranial portion of the rumen They occur at the end of a primary contraction cycle
209
What are the steps of the secondary contractions?
(1) Cranial-moving contraction starting in the caudo-dorsal blind sac
(2) Forward-moving contraction of the dorsal sac that moves gas toward the cardia. Gas will enter the esophagus and can then be eructated.
210
What is the regurgitation reflex? How frequently does this occur?
Function is to bring large particles from the rumen back to the mouth so that it can be chewed to reduce particle size
Normal frequency: 1 regurgitation every 2-3 min (60% of the cows in a herd should be actively chewing the cud)
211
What are the steps to the regurgitation reflex?
(1) It begins with a contraction at the mid-dorsal rumen and this pushes the gas cap caudally and the big particles toward cardia
(2) The lower esophageal sphincter relaxes and the bolus enters the esophagus and propeled to the mouth by antiperistalsis
212
What are the gases produced during rumen motility?
The gases produced during rumination are mainly carbon dioxide (60-70%) and methane (30-40%)
Traces of nitrogen, oxygen, and hydrogen might be present (intermediaries for other reactions)
213
What is the eructation frequency?
Eructation frequency is about 1/min
214
What is the eructation center? Where is it located?
Eructation center is localized in the medulla and receives afferent fibers from mechanoreceptors placed in the dorsal sac of the rumen (where gas accumulates)
215
What is tympanism? What can cause this?
Tympanism or bloatting occurs in cattle when the eructation mechanism fails.
Causes include:
- Blockage of the esophagus
- Impaired vagal nerve function
- Rabies
- More typical due to the ingestion of legumes
216
What is legume bloat? What is the treatment?
Legume bloat: when cattle feed on lush, rapidly growing alfalfa or clover pastures (contain waxy saponins). Gas becomes trapped in tiny bubbles and the normal free gas bubble cannot accumulate on top of the dorsal sac of the rumen -\> the presence of gas is not detectable by the mechanoreceptors of the dorsal sac
Introduce trochar to deflate cow
217
What controls reticulorumen motility?
ENS / Vagus Nerve
Control center for reticulorumen motility is located in the brainstem (dorsal vagal nucleus) -\> efferent fibers go to the rumen with the vagus nerve
218
What is the job of stretch receptors and chemoreceptors?
monitor distention, consistency of the ingesta, pH, VFA concentration, ions
219
What is the esophageal groove or the reticular groove? What is its purpose?
```
Esophageal groove (reticular groove) is a gutterlike invagination traversing the wall of the reticulum from the cardia to the reticulo-omasal orifice
It diverts milk away from the developing rumen and pass it directly to the abomasum
```
220
What is the kind of action of reticular groove closure? What stimulates it? And What occurs mechanically when it is stimulated?
Reticular groove closure is a reflex action (brainstem impulses arrive through the vagus) Afferent stimuli arise from centrally (anticipation of suckling -\> cephalic phase) and from the pharynx (suckling) When stimulated, muscles of the groove contract causing it to twist -\> lips of the groove close together forming a tube from the cardia to the omasal canal
221
What is ruminant ketosis?
Ruminant ketosis (and associated hypoglycemia) occur most frequently in high-producing dairy cows (usually within 6 weeks after calving or in late gestation)
222
what is the normal pathway of acetate and butyrate entering the krebs cycle?
Acetate, butyrate -----\> acetyl CoA ------\> citrate Provided there is enough oxaloacetate
223
What occurs if there is not enough oxaloacetate/ if there is an excessive amount of acetyl coa in ruminants?
If oxaloacetate is not enough or if the amount of acetyl CoA is excessive (excess oxidation of fat), acetyl CoA accumulates as acetoacetyl CoA which is subsequently degradated to acetoacetate, beta-hydroxybutyrate, and acetone (ketone bodies)
224
What is required for acetate and butyrate to enter the Krebs cycle?
Oxaloacetate
225
What animals are hindgut fermenters? What kind of waves do you have in the LI of these animals?
Horses.
Peristaltic and antiperistaltic waves
226
In horses what are potential sites of impactions? What does this make them more prone to? What can be done to prevent this?
- Any area of narrowing intestine can be a site of impaction. This makes them more prone to colic. Ingesta must be very fine to prevent this.
227
What conditions are essential for maintaining fermentation in hindgut fermenters?
1) Substrate supply
2) Control of pH (buffers)
3) Osmolality
4) Anaerobiosis
5) Retention of fermenting material
6) Removal of waste product and residue
228
What is the predominant motility pattern of the cecum in hindgut fermenters? the ventral colon?
The predominant motility pattern in the cecum is of mixing nature with low-amplitude contractions that move the ingesta from haustra to haustra
The predominant motility patterns in the ventral colon are haustral segmentations, propulsive peristalsis, and retropulsive peristalsis
Small particles flow to distal leaving the ventral colon
Big particles are retained
229
What do mechanism do ruminants have for digestion that horses do not? Rabbits also have something like this, what is it called?
In contrast to the ruminant, horses do not have a mechanism to recover and utilize microbial proteins and most of them passes out in the feces (cecotrophy in rabbits helps recover microbial proteins)
230
What is the benefit of ingesta passing through the stomach and small intestine before arrival in large intestine in hindgut fermenters?
Ingesta passage through the stomach and small intestine before its arrival to the large intestine -\> exposure to gastric acids and digestive enzymes may increase the digestion rate in the hindgut
231
Where is the urea recycling occuring in the ruminant? In the hindgut fermenter?
Hindgut: Colon and Cecum
Ruminant: Rumen
232
Who is more efficient at degrading cellulose?
Ruminants
233
Who is more efficient at absorption of VFA?
Ruminants
234
Who is more efficient at utilizing microbial protiens?
ruminants
235
Who is more efficent at digesting food of poor quality?
Horses
236
Who is more efficient at dealing with scarcity of food?
Ruminants (better at digesting/ absorbing)
237
Where does most carbohydrate digestion in ruminants occur?
Most carbohydrate digestion in ruminants occurs in the forestomach through fermentative digestion . Almost no digestible carbohydrate enters the intestine
238
What process do ruminants get their glucose from?
gluconeogenesis
239
What is the most important precursor of glucose in ruminants?
The VFA propionate
240
What level does propionate enter the Krebs cycle? What is it? What can it lead to?
Propionate enters the Krebs cycle at the level of succinate
Succinate is a 4 carbon intermediate that can lead to the formation of oxaloacetate which is the entry metabolite for gluconeogenesis
241
What percentage of glucose needs in ruminants is met by glucogonogenesis?
Gluconeogenesis covers ~85 - 100% of glucose needs
242
TRUE or FALSE: Ruminents always make enough glucose (and then some) to satisfy their needs?
FALSE: Ruminants exist in a constant state of potential glucose deficiency
243
What regulates insulin in ruminants?
Insulin levels are regulated by the concentration of VFA
244
Where is the propionate absorbed from and where does it originate from?
Almost all propionate absorbed from the rumen is extracted from the
portal blood by the liver and never enters the systemic circulation
245
Where are fatty acids synthesized in ruminants and what does this help them do ?
In ruminants, fatty acids are synthesized only in the adipose tissues using acetate as a precursor molecules and never glucose.
Ruminants also effectively conserve glucose
246
In high producing dairy cows, where does nearly all the glucose go? What is their energy source?
In high producing dairy cows nearly all the glucose they produce goes to lactose (milk sugar); the remaining tissues function on alternative fuel
247
What structures do avians not have in their digestive system?
- No soft palate, no teeth
248
what terminates at the cloaca?
Digestive, urinary and reproductive discharges
249
What do grain eating birds swallow and why?
Grain-eating birds swallow stones and gravel (grit) to help grind the food
250
What is true about Ceca in birds?
Ceca are paired in some species; in others they are rudimentary
251
TRUE or FALSE: Esophagus is large in diameter
TRUE
252
What are acids, strong acids, and weak acids?
• Acids: Donate hydrogen ions (protons) to make solution acidic
◦ Strong acid: Protons can completely dissociate in aqueous solutions.
◦ Weak acid: Protons dissociate incompletely in solutions.
253
What are bases, strong bases, and weak bases?
• Bases: Bases accept hydrogen ions and release OH-
◦ Strong base: Releases OH- completely in aqueous solutions.
◦ Weak base: Does not completely accept protons in an aqueous solution.
254
What is the relationship between pH and hydrogen concentration?
• Since it is negative Log 10 [H] then increased Hydrogen will result in decreased pH and decreased Hydrogen will result in increased pH
255
1. What are the common acids produced in the body?
* CO2
* Metabolism of proteins ( Sulfuric and phosphoric acids)
* Fats (ketoacids)
* Incomplete Oxidation of glucose (lactic acid)
256
What are the primary functions of buffers in maintaining acid- base balance?
• Buffers: Substances (chemicals/ proteins) that reversibly bind or release H+ , fast acting, responding to small pH changes. Cannot eliminate acids or bases from body.
257
What are the primary functions of the respiratory system in maintaining acid- base balance?
• Respiratory System: Maintain normal blood pH by altering CO2 removal rate from the blood. Responds slower than buffers but faster than kidneys.
258
What are the primary functions of the kidney in maintaining acid- base balance?
• Kidneys: Eliminate or retain H+, slow acting, responds to large pH changes.
259
Which reaction requires carbonic anhydrase?
Carbonic anhydrase catalyst is found within the body and can speed up the conversion of H2O + CO2 -\>
260
What is the dissociation constant (Ka)?
Ka (dissociation constant) = ([H+][HCO3-])/[H2CO3]
261
When HCL is added to the bicarbonate buffer, what happens?
• The reaction will quickly remove H+ ( being transformed into carbonic acid) in order to maintain pH
262
When NaOH is added to the bicarbonate buffer, what happens?
• The reaction will remove the hydroxide ion by having it bind to the H2O. Since this occurs the reaction will go up to maintain the pH and give a hydrogen to the lost.
◦ If not removed the hydroxide ion will increase the pH too much.
263
What is pKa?
• The pKa for buffer system is the pH at which there are equal amounts of the weak acid and its conjugate base
264
What is the required ratio of HCO3-/H2CO3 to make this buffer effective in maintaining acid-base balance?
20: 1
265
How do red blood cells help maintain normal pH in the tissues?
• Oxyhemaglobin will give off its O2 to the tissue and hb will take on a hydrogen from the increasing hydrogen content in the RBC and become deoxyhemaglobin. This will keep the pH more normal. Since it is closer to the normal pH than oxyhemaglobin
266
What do peripheral chemoreceptors sense?
• Peripheral chemoreceptors are located in the aortic arch or in the carotid bodies, and this detects hydrogen in the blood.
267
What do central chemoreceptors sense?
CO2
268
Which part of the central nervous system controls the respiratory rate?
PONs
269
Check w/ Caroline: How does the respiratory system help maintain acid-base balance?
* When increase of H+ is sensed in the blood the brain will send signal to respiratory system to decrease CO2 in the system, this will bring down hydrogen
* When CO2 is increased in the blood (via central chemoreceptors) central and peripheral chemoreceptors work together to regulate the CO2 in the blood.
270
What are titratable acids?
• Solutes filtered in base forms at glomeruli and bind secreted protons in the tubule fluid.
271
Why isn’t ammonia a titratable acid?
• Not filtered at glomeruli as base form
272
What is renal net acid excretion (NAE)?
• Renal Net acid excretion is sum of urinary titratable acids, plus urinary ammonium, minus urinary bicarb
273
How do the proximal convoluted tubule and thick ascending limb maintain normal pH?
* Proximal tubule and thick ascending limb are the major places that robustly reabsorb HCO3- and secrete hydrogen ions, but dont significantly change the pH of the tubule fluid
* Bicarb filtered out of tubule into the lumen of Blood vessels. It combines with Hydrogen to form H2CO3. This will be catalyzed by carbonic anhydrase and will be broken down to CO2 and H2O. This then moves into the epithelial cells where it will react with carbonic anhydrase to form H2CO3 again. This then then will be dissociated into Hydrogen and bicarbonate ( by ATPase). Bicarbonate is reabsorbed into the blood by cotransporter/ exchangers ( Sodium bicarb transporter and Cl-/HCO3- exchanger). The hydrogen will be excreted into the lumen again and can become ammonium or H2PO4-.
* Carbonic acid cannot pass membrane so this is why it must be broken down first then reassembled.
* pH will be maintained at 7.4
274
What do the type A intercalated cells in the collecting duct do?
Type A cells are acid secreting cells.
275
What do the type B intercalated cells in the collecting duct do?
Type B cell : base secreting cells
276
How does the kidney secrete ammonium?
• Renal ammonia ( in ammonium form) is generated in the proximal convoluted tubules it is called ammoniagenesis. This flows through renal tubules, and at the thick ascending limb of henles loop the NH4+ is resorbed. Most NH4+ will just stay and not go back into the blood. Some may go back to renal tubule at thin limb of henles loop. Some of the ammonia will go to the collecting duct where it will bind to the secreted/ excreted hydrogen to recreate ammonium.
277
In addition to ammonium, what else is produced from glutamine in the proximal tubule cells?
• bicarb HCO3-
278
What molecules are bound to ammonium in the medullary interstitium of the kidney?
Ammonium will bind to sulfatides
279
What are the differences in ammonium excretion in different species?
* In mice, rats, dogs, chickens, and humans, ammonia excretion accounts for up to 60% of renal net acid excretion (NAE) in basal conditions and can increase to 90% NAE in models of metabolic acidosis.
* Other species may be different. For example rabbits have low basal urinary ammonia excretion rates and do not increase ammonia secretion during metabolic acidosis.
280
What are the major causes and characteristic findings of respiratory acidosis?
• Causes: Damage/ depression to respiratory control centers, Respiratory pump injury (fractured ribs, bloated abdomen), Severe respiratory disease that obstructs airways or excessively stiffens the lungs.
• Findings
◦ Primary abnormalities:
‣ Increased PaCO2 \> 40 mmHg
‣ increased H+
‣ decreased pH \<7.35
◦ Compensatory changes:
‣ increased HCO3- (minor and insufficient)
‣ Renal: Increased H+ and NH3 production, elimination H+ in urine, generate new HCO3-
◦ All of these will bring pH towards normal.
281
Which cells’ function in the kidney’s collecting duct is enhanced during respiratory acidosis?
Type A cells
282
What are the major causes and characteristic findings of respiratory alkalosis?
• Causes: Stimulation of chemoreceptors by hypoxemia, Stimulation of intrapulmonary receptors by lung injury, Over use of ventilator.
• Findings
◦ Primary abnormalities:
‣ Decrease PaCO2 \< 40 mmHg
‣ Decrease H+
‣ Increase pH \> 7.35
◦ Compensatory changes:
‣ Decrease HCO3- (minor and insufficient)
‣ Renal: Increased elimination of HCO3- due to decreased production of H+ and NH3 (alkalosis)
283
Which cells’ function in the kidney’s collecting duct is enhanced during respiratory alkalosis?
Type B cell
284
What are the major causes, compensatory changes, and treatment of metabolic acidosis?
Causes:
• Increase in H+ production:
◦ Protein catabolism or ketone production during negative energy balance
◦ Anaerobic metabolism that leads to lactic acidosis
◦ In ruminants, excessive feeding of carbohydrates leads to increased H+ production in the rumen (rumen acidosis) • Failure of H+ elimination by the kidney
• Loss of buffer base:
◦ Diarrhea---excessive amounts of HCO3- are lost in the feces
Primary abnormalities : Increased H+, Decrease pH \<7.35, Decrease HCO3-
Treatment: IVF containing buffers (I.e lactate or bicarbonate). Restoration of depleted base by kidney.
285
What are the major causes, compensatory changes, and treatment of metabolic alkalosis?
Causes:
• Most common loss of H+
• Vomiting
• In ruminants RDA leads to trapping of H+ ions in the abomasum
• K+ depletion (hypokalemia) results in increased H+ secretion by the kidney.
Primary: Decrease H+
• Increase pH \>7.35
• Increase HCO3-
Compensatory: Increase in PaCO2 \>40 mmHg due to increased respiratory rate
Treatment: IVF ( saline, potassium, HCl)
◦ Cure diseases that cause the metabolic alkalosis
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How can you diagnose acid-base disorders using arterial blood gas?
**Normal:** pH, PaCO2, HCO3- all within normal range
**Respiratory acidosis; Partially compensated:** pH and PaCO2 acidotic, HCO3- alkalotic
**Respiratory Acidosis; Fully Compensated:** PaCO2 Acidotic, pH Normal, HCO3- Alkalotic
**Metabolic acidosis; uncompensated:** pH and HCO3- Acidotic, PaCO2 normal.
**Metabolic acidosis, fully compensated:** HCO3- Acidotic, pH normal, PaCO2 Alkalotic.
**Respiratory Alkalosis; partially compensated :** HCO3- Acidotic, pH and PaCO2 alkalotic.
**Metabolic Alkalosis; uncompensated:** PaCO2 Normal, pH and HCO3- alkalotic
**Mixed metabolic and respiratory acidosis; uncompensated**: PaCO2, pH, HCO3- alkalotic
**Respiratory alkalosis; partially compensated:** HCO3- acidotic, pH and PaCO2
**Metabolic acidosis; partially compensated:** pH, HCO3- acidotic, PaCO2 alkalotic
287
What result would indicate normal acid-base?
Normal: pH, PaCO2, HCO3- all within normal range
288
What lab results would indicate partially compensated respiratory acidosis?
Respiratory acidosis; Partially compensated: pH and PaCO2 acidotic, HCO3- alkalotic
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What lab results would indicate uncompensated metabolic alkalosis?
Metabolic Alkalosis; uncompensated: PaCO2 Normal, pH and HCO3- alkalotic
290
The external anal sphincter is innervated by what nerve. Is it sympathetic or parasympathetic? Internal anal sphincter?
External: Pudendal nerve (sympathetic)
Internal: Pelvic (parasympathetic)
291
How do neurohormones differ from neurotransmitters?
• Neurohormones are secreted by neurotransmitters, then are released into the blood to go to target organs. Neurotransmitters only have action at a small volume where release occurs, but neurohormones can have a wide variety of action across many targets, possibly very away from the site of synthesis. Neurohormones, however, are released systemically.
292
Define endocrine, paracrine, autocrine, intracrine, and exocrine.
utocrine- secreted and acts on same cell.
Paracrine- doesnt travel through blood, effects nearby cell
Endocrine- produced in one tissue and needs to go though bloodstream to target organ
Intracrine- Never leaves cell, acts on self within cell.
Exocrine- hormones released into body cavity such as the hormones produced by pancreas and released into body cavity
293
What are the two characteristics of hormones?
* Amplification: Small amounts of hormones can produce significant biological effect.
* Slow action: Effects of hormones can last minutes to days ( nervous system: milliseconds to seconds)
294
What are the differences in the synthesis between protein hormones and steroid hormones?
◦ Steroid Hormone: Lipid droplets stored in the cell are first converted back to cholesterol. The next step step in the synthesis of all steroid hormones from cholesterol involves cleavage of the side chain of cholesterol to form pregnenolone; this step occurs within the mitochondrion. After this the steroid hormone pathway continues into the ER and then returns back to mitochondria for final steps and then can be secreted immediately
◦ Protein Hormone:Protein hormones are initially synthesized as preprohormones in ribosomes and then cleaved in the rough endoplasmic reticulum to form prohormones and in the Golgi apparatus to form the active hormones, which are stored in granules before being released by exocytosis.Calcium content is increased within cell to help vesicles fuse with membrane to preform exocytosis.
295
Cholesterol synthesis, transport, and storage?
* Cholesterol is synthesized in the liver and delivered by LDL
* HDL will take cholesterol from the cell and bring it to the liver.
* LDL and VDL bring cholesterol/ triglycerides to the cell.
* Cholesterol is stored in lipid droplets or used immediately to make steroid hormones.
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6. What are the differences in transportation between steroid and protein hormones?
* Hydrophilic hormone binds to receptor in plasma membrane. which activates second messenger. This delivers message to the nucleus.
* Hydrophobic hormones can diffuse through the plasma membrane. Hormone binds to receptor and then moves int the nucleus.
297
7. What are the differences in metabolism between steroid and protein hormones?
• Hormone Metabolism:
◦ Steroid hormones:
‣ Reduction followed by conjugation with sulfates and glucuronides.
‣ Increased solubility of the steroids, allowing them to be excreted in the urine. Mainly occurs in liver.
◦ Protein Hormones:
‣ Reduction of disulfide bonds
‣ Cleaved by peptidases.
298
What are the characteristics of hormone-receptor interaction?
* Specificity
* High Affinity
* Reversible (non covalent)
299
What are the two primary mechanisms to terminate hormone-receptor interaction?
* dissociation- dependent on hormone concentrations
* Endocytosis and degradation by lysosomes
300
What occurs intracellularly in hydrophobic hormones?
• Hormone binds to receptor and is activated -\>then will be translocated into the nucleus, and then bind to sequence of DNA called "the response element". This binding will initiate new mRNA transcription, which will go to cytoplasm and produce new proteins
301
What occurs intracellularly in hydrophillic hormones?
• Hydrophillic hormones cannot pass the cell membrane so the hormone binds to receptor which then binds to a 2nd messenger to deliver message into the cell to produce biological signal.
302
How do the second messengers, i.e., cAMP and IP3/DAG, work in cells?
* cAMP: Cyclic AMP is one of these 2nd messenger. Enzyme is called adenocyclase this can convert ATP into cyclic AMP. This CAMP can then convert inhibitory catalytic subunit to just a catalytic subunit which could then phosphorylate other proteins/ enzymes and eventually provide transcription factors that can bind to the DNA sequence. The CAMP can then be broken down by PDE to AMP to remove it from the body.
* IP3/DAG: Hormone binds to receptor in plasma membrane. Receptor leads to G protein, and the G protein binds to GTP. This will activate phospholipase C. This will produce ITP3 and DAG. ITP3 can bind to calcium channel in the endoplasmic reticulum membrane into the cytoplasm. Ca++ concentration in ER is high, so the influx of Ca++ from the ER to the cytoplasm will activate alot of molecules. DAG and Ca++ can also activate Protein Kinase C which can also activate other transcription factors. Calcium will then pump back into lumen of the ER.
303
1. What are the differences in hormone production between anterior and posterior pituitary glands?
* Posterior Pituitary gland: Cannot produce own hormones.
* Anterior pituitary can produce own hormones and release into the blood. .
304
What are hormone production's positive and negative feedback regulations when an animal is in heat?
* When canine is in heat (ovulation) before ovulation ovary produces estrogen and blood will contain elevated luteinizing hormone After ovulation their is an increase in progesterone and estrogen/ luteinizing hormone will decrease.
* Positive -\> GnRH causes stimulation of LH which stimulates ovary to produce estrogen. Estrogen (positive feedback ) increases LH production and GnRH production
* Negative -\> Progesterone produced by the ovary (negative feedback) - Which will inhibit GnRH and this will significantly decrease LH production and decrease in estrogen
305
\*\*How are the six major anterior pituitary hormones regulated either negatively or positively?
* LH, FSH -\> Positive feedback of GnRH, Negative Feedback -\> Progesterone
* TSH -\> Positive feedback ( TRH) Negative Feedback -\> Dopamine, or increase of T3, T4
* GH -\> Positive feedback (GHRH ) Negative Feedback -\> GHIH (somatastatin)
* Prolactin -\>Positive feedback ( PRF) Negative Feedback -\> prolactin inhibiting hormone (dopamine)
* ACTH -\> Positive feedback (CRH), Negative Feedback -\> Cortisol increases, stress
306
What are the target organs and regulation of the six major anterior pituitary hormones?
FSH,LH -\> ovaries in female, testes in male -\> Regulated by GnRH produced by hypothalamus
TSH -\> Stimulates Thyroid hormone in thyroid-\>Produced by hypothalamus. Stimulated by TRH but inhibited by dopamine.
GH -\> acts on liver. Most mediated by IGF-1 and can stimulate growth of bone, fat or muscle. Hypothalamus stimulates GHRH which will stimulate production of growth hormone in the anterior pituitary gland. Hypothalamus also produces GHIH (somatastatin) which will inhibit growth hormone production.
Prolactin-\> Mammary Glands -\> Prolactin regulated by prolactin releasing factor from hypothalamus (stimulatory hormone) and prolactin inhibiting hormone (dopamine) which is also produced in the hypothalamus. Dopamine will inhibit prolactin while prolactin releasing factor is stimulatory.
ACTH -\> Adrenals -\> Hypothalamus releases Corticotropin releasing hormone (CRH)-\> which is sent to anterior pituitary gland which then stimulates production of ACTH.
307
What are the major causes, clinical manifestations, and diagnoses of Pituitary Dwarfism?
* Autosomal recessive inherited. Destruction of pituitary gland.
* German Shepard: 20%
* Clinical Signs: Slow growth, mental retardation, retained puppy hair coat, hypotonic skin, delayed dental eruption.
* Dx: IGF-1 / Serum Growth Hormone. (decreased)
* Not enough pituitary hormone being produced
308
What are the major causes, clinical manifestations, and diagnoses of Acromegaly?
◦ Causes: Pituitary adenoma/ hyperplasia.
◦ Cats: 8-14 years old
◦ Clinical Manifestations: Uncontrolled diabetes mellitus, polyuria, polyphagia, weight gain, hepatomegaly, ect.
◦ Dx: CT, MRI, of pituitary region/ Serum IGF-1 (increased)
• Too much function in pituitary gland.
309
What are the major steps of vasopressin synthesis?
• synthesized within cell within the hypothalamus and are carried via axon flow to the posterior lobe where they are located
• Magnocellular neurons ( Hormone production in hypothalamus)
1) Prepropressophysin leaves ER of magnocellular neuron
2) Signal peptide is removed and result is propressonphysin.
3.) This is contained within a vesicle and travels through axon
4.) during transport, this is further cleaved and forms another form of the peptide.
\*Fxn of NPH is unlcear
5) Secreted out of posterior pituitary into blood with stimulation, otherwise it just waits at the entrance until it is stimulated.
310
What are the major stimuli for vasopressin secretion?
◦ Osmolarity (osmo receptor are within the hypothalamus)
◦ Blood Volume (Blood volume receptor in the atrium of the heart)
311
How are the two vasopressin receptors and their functions?
- vasopression 2 in kidneys - \> Retain water -\> increase Blood volume, decrease osmolarity
• Vasopression 1 in blood vessels -\> vasoconstriction-\> Increased blood pressure
312
How does vasopressin increase water reabsorption in the kidneys?
Vasopressin will bind to receptor and use second messenger ATP (which is changed by adenylyl cyclase to cAMP). This will then cAMP will convert inactive PKA to active PKA. Which will then convert protein substrates into phosphorylated proteins. Phosphorylated will enhance the insertion of vesicles with Aquaporin AQP2. Exocytic insertion will insert aquaporin to the apical membrane
313
The causes of central and nephrogenic diabetes insipidus?
* Central DI: Defective secretion of ADH in posterior Pituitary gland
* Nephrogenic DI- Inability of the renal tube to respond to ADH
314
How do the modified water deprivation test and the ADH response test help differentiate central diabetes insipidus from nephrogenic diabetes insipidus?
• Modified water deprivation test will test to see if endogenous ADH is released in response to dehydration.
315
What are the primary stimuli for oxytocin secretion?
stretch of cervix in late pregnancy. -\> signal to hypothalamus -\> oxytocin produced / released by posterior pituitary gland
Suckling of nipple. -\> signal to hypothalamus -\> oxytocin produced / released by posterior pituitary gland.
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What are the major functions of oxytocin?
◦ Stretch of cervix in late pregnancy. (effect: contraction of uterus muscle)
◦ Suckling of nipple. (effect: Myoepithelial cell contraction and milk ejection).
317
Why is bicarbonate buffer is the most critical physiological buffering system?
bicarbonate has pka of 6.1 which is not ideal in normal physiologic conditions. The bicarbonate buffer system is also an open system that can be regulated, and there is a large amount of HCO3- in the blood. The lungs can regulate CO2 and change H2CO3 concentration, as well as the kidney being able to regulate HCO3 - concentration.
318
How does the kidney secrete titratable acids?
Is it just knowing that H+ from lumen will bind to HCO3- and HPO4 to create H2CO3and H2PO4 which gets secreted into the collecting ducts and is excreted via the urine
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