QUIZ 5 Flashcards
(294 cards)
1
Q
Chemical energy
A
- fuel for cellular work
- ingested organic molecules are broken down and potential energy of their covalent bonds is converted to ATP
- energy cant be created or destroyed
- different amounts of ATP are derived from different food molecules
- one calorie= energy required to raise 1 ml of water 1 C
- food calories are kilocalories
- lipids (triglyceride) -> 120 ATP/steric acid -> 9kCal/gram
- carbs -> 30 ATP/glucose -> 4kCal/gram
- proteins -> 30 ATP/amino acid -> 4kCal/gram
2
Q
organic precursors
A
organic raw materials for biosynthesis (carbon skeleton)
–digest proteins down to amino acids and use to make our own nutrients
3
Q
essential nutrients
A
substances animals cannot synthesize
4
Q
dietary water
A
water ingestion/production of metabolic water
5
Q
dietary needs
A
- repackage energy in covalent bonds in food into ATP
- ATP energy currency -> work
6
Q
lipids
A
- most common lipid we digest is tryglyceride -> 3 fatty acids and one glycerol
- glycerol covalently linked to carboxyl group of fatty acid
- molecule that dissolved in a nonpolar solvent
- ex. cholesterol
7
Q
unsaturated
A
- double bond present
- there could be H there
- presents a kink
- liquid at room temp
- oleic acid
- cis double bond
8
Q
ester linkages
A
- joins glycerol to carboxyl group of fatty acid
- middle fatty acid can rotate
9
Q
phospholipid
A
- glycerol attached to two fatty acids and one phosphate group
- bilayer
- phosphate it on exterior (hypdrophilic)
- fatty acids on interior (hydrophobic)
10
Q
saturated fats
A
- straight (no kink)
- H bonds all around
- solid at room temp
- stearic acid
- can be more a risk for cardiovascular disease
11
Q
steroids
A
- lipid related molecules whose structure includes four linked carbon rings
- cholesterol is primary source of steroids in human body
12
Q
chemical energy: carbohydrates
A
- monosaccharides (fructose, glucose)
- disaccharides (sucrose)
- polysaccharides
13
Q
alpha glycosidic linkages
A
- digestable
- same side
- ex. glycogen, starch
14
Q
beta glycosidic linkages
A
- non digestable
- alternating -> allows for hydrogen bonds between neighboring chains -> cross bridges
- ex. chitin, cellulose (1-4 linkage of beta glucose)
15
Q
sucrose
A
- fructose + glucose = sucrose
- alpha glycosidic linkage
- table sugar
- digestable
16
Q
dextrose
A
- term for glucose
- in 0 calorie sweeteners
- its actually 4 calories
- agonist binds to receptors -> sweet taste response
17
Q
starch
A
- alpha 1-4 linkage of alpha glucose -> amylose -> linear chain
- alpha 1-6 linkages -> branched -> amylopectin
- polymer
18
Q
glycogen
A
- highly branched
- polymer
19
Q
polymers
A
- stores glucose (monomers) as polymers
- if you tried to store monomers it creates too much osmotic pressure created by many individual monomers
- pack more as polymers
- glycogen & starch
20
Q
proteins
A
- chains of amino acids
- central carbon
- amino group
- hydrogen
- carboxylic acid group
- side chain (R)
21
Q
peptide bonds
A
- links amino acids
- formed by ribosomes
22
Q
dehydration synthesis
A
- produces water
- links two structures by removing water
- forms polypeptide
- directional
23
Q
primary strucutre
A
-linear sequence of amino acids
24
Q
secondary structure
A
- folds in characteristic ways
- beta pleated sheets- antiparallel or parallel, amine hydrogen and carboxylic oxygen form H bonds
- alpha helix- carbonyl oxygen interacts with H of amine group (hydrogen bonds) -> 3.6 amino acids per turn
25
tertiary structure
- interactions between R groups
- chaperones help fold correctly
- once they been denaturation does not refold into protein
26
quaternary structure
- hemoglobin
| - more than one polypeptide interaction
27
denaturation
- hydrochloric acid in stomach denatures proteins for digestion
- H ions denatures
- enzymes then have excess to cleave bonds
28
Essential nutrients
- substances the body is unable to synthesize from organic precursors
- essential amino acids
- essential fatty acids
- vitamins
- minerals
- malnutrition- state of insufficiency of an essential nutrient
29
essential nutrients: amino acids
1. methionine
2. valine
3. threonine
4. phenylalanine
5. leucine
6. isoleucine
7. tryptophan
8. lysine
- histidine (required for newborns)
- 1-6 found in corn and other grains
- 2-8 found in beans and other legumes
- meat & fish fulfill these
30
essential nutrients: fatty acids
1. alpha-linolenic acid
2. linoleic acid
- omega 3 fatty acid
- omega 6 fatty acid
- require through diet
- ex. olive oil
31
essential nutrients: vitamins
-organic molecules required in small amounts
Fat soluble (accumulate in body):
-A: visual pigments, gene regulation
-D: allows dietary calcium to be absorbed
-E: antioxidant
-K: blood clotting
Water soluble (easily eliminated in urine):
-B complex: coenzymes -> many, deficiency can cause diseases
-C: antioxidant- connective tissue synthesis -> scurvy
32
antioxidants
- protect against the oxidative effects of O2
| - vitamin E and C
33
essential nutrients: minerals
- inorganic substance needed in small amounts
- calcium: 2nd messenger muscle contraction
- sodium, potassium, chloride
- iodine: thyroid hormone
- iron: hemoglobin (O2 transport)
- Mn, Co, Cu, Ni, Zn, S: enzyme cofactors
34
digestion occurs in specialized compartments
- intracellular digestion: specialized organelles: vacuoles
| - extracellular digestion: gastrovascular cavities, alimentary canals
35
intracellular digestion
- vacuoles
- unicellular
- brings food (bacteria) in through oral groove
- cytosome- specialized for endocytosis-> consumes food
- pendocytosis- taking in liquid
- food vacuole forms and is digested
- absorbs essentials
- exocytosis of waste through anal pore
36
gastrovascular cavities
- single opening to the outside used for both ingestion and elimination
- ex. hydra, flatworms (planarians)
- allows animal to consume larger prey than could be ingested and digested intracellularly
- cellular specialization- cells for secretion of acid, enzyme, and hormones; cells for absorption of nutrients
37
hydra
- gastrovascular cavities
- 10mm
- anchored by basal disc
- no anus
- cnidarians
- tentacles (stingers)- neurotoxins paralyze animal
- gas exchange occurs in the same cavities
- nutritive cells
- flagella creates current
- gland cells- digestive enzymes
38
alimentary canals
- two openings to the outside, one for ingestion (mouth) and one for elimination (anus)
- tube extends between openings
- food generally moves through the tube in one direction (with some exception- vomit)
- specialized regions within tube for digestion and absorption in a stepwise fashion
39
alimentary canal: birds
- lack teeth
- esophagus leads to crop
- crop- used for food storage
- moves to glandular stomach- chemical digestion
- move to gizzard- muscular organ that mechanically digests
- food can move backward from gizzard to stomach for more chemical digestion
- moves to intestine then anus
40
alimentary canals: humans
-esophagus to stomach
| -
41
sphincters
-control movement through GI tract
-upper and lower esophageal
-lower sphincter- prevents stomach acid backflow -> defect -> heart burn
-anal sphincter
-pyloric sphincter
Alimentary canal:
-oral cavity (mouth)
-esophagus
-stomach
-small and large intestine
Accessory organs:
-salivary glands
-liver
-gallbladder
-pancreas
42
layout of alimentary system
- Ingestion/digestion- oral cavity -> pharynx -> esophagus
- storage/grinding digestion- crop -> stomach -> gizzard
- digestion/absorption- intestine
- elimination- anus
43
oral cavity
- ingestion
- mechanical digestion
- teeth, tongue, muscles, jaw
- carnivores- sharp teeth
- omnivores- molars
- food is ground into smaller particles to provide greater surface area for digestive enzymes
- initial chemical digestion of carbohydrates -> salivary amylase
44
oral cavity: saliva
- salivary glands- exocrine glands
- produced by salivary glands:
1. parotid gland
2. sublingual gland
3. submandibular gland
- hypotonic solution
- triggered by presence or anticipation of food
- functions:
- lubricates mouth and food to facilitate swallowing: mucins (glycoproteins)
- begins carbohydrate digestion- salivary amylase breaks starches into smaller polysaccharides
- protects from invading microbes- immunoglobulins, enzymes, resident microbes
- balance: ion and buffers
- taste molecules need to be dissolved in saliva in order to taste
45
parotid gland
- salivary exocrine gland
| - rich in enzymes like amylase
46
sublingual gland
- salivary exocrine gland
- rich in mucins
- lubricates food to swallow
- glycosylated proteins that are viscous
47
submandibular gland
- salivary exocrine gland
| - mixed, with both enzymes and mucins
48
salivary gland
- Na/K ATPase pump -> creates gradient for sodium reabsorption
1. Acinar cells secrete extracellular fluid with proteins enzymes -> isotonic to ECF
- aquaporins are present here and water follows solute into duct
2. in the duct of the gland NaCl is reabsorbed and HCO3 & K are secreted -> hypoosmotic to blood plasma
- no aquaporins in duct
49
oral cavity: tongue
- dissolved molecules enter the taste pore
- several cells inside the taste pore allow to detect taste
- must be dissolved in saliva
- sweet, salt, bitter, sour, umami
- type 1 support cells- may sense salt
- receptor cells (type 2)- detect sweet, umami, and bitter
- presynaptic cell (type 3)- detects sour
50
umami
- savory
- meat
- amino acid glutamate stimulates receptors for detection of umami
51
bitter
- avoidance mechanism
| - toxins are bitter
52
receptor cells (type 2)
- detect sweet, umami, and bitter
- g-protein coupled receptor
- binding -> gustducin -> influx of Ca -> release of ATP through channels -> paracrine signals and binds to primary sensory neuron or neighboring cells -> action potential fire
- detects glutamate (umami)
- release ATP when ligand binds to their g-protein couple receptor, acts in paracrine matter
- ATP works as signal
- ATP binds to primary sensory neurons -> stimulates nerve
- ATP can also bind to neighboring cells
53
presynaptic cell (type 3)
- forms synapse with primary sensory neurons
- neurotransmitter is serotonin
- channel that conducts H ions
- senses H+ ions or decrease in pH -> H+ enters through channel -> H+ closes K channels -> decrease in K -> depolarization -> Ca influx -> serotonin released by exocytosis -> synapse with primary gustatory neurons
54
deglutition
- swallowing
1. tongue pushes bolus against soft palate (top) and back of mouth, triggers swallow reflex
- back of throat (pharynx) has sensory pressure receptors -> sensory afferent neurons send signal to medulla oblongata -> swallow -> move down esophagus -> smooth muscles contract behind bolus -> peristalsis -> moves bolus into stomach
- saliva keeps pieces of food together
55
spicy
- binds to pain receptors
| - somatosensory pathways
56
epiglottis
- cartilage
- as we swallow closes and blocks trachea
- aspiration- food moves in airway
57
pharynx/esophasgus
- conducts bolus of food to stomach by creating pressure gradients: bulk flow
- in humans:
- striated skeletal muscle at top of esophagus (voluntary)
- smooth muscle in lower esophagus (involuntary peristalsis)
- salivary amylase continues to digest starch and glycogen
58
peristaltic contraction
- contracts behind to bolus
- smooth muscle- involuntary
- relaxed in front of bolus so it can be propelled forward
- seconds after it happens again
- controlled by enteric nervous system
- rhythmic contractions
59
swallowing
- starts out voluntary
- once it hits the back of the throat (pharynx) there is feedback loop to the medulla
- efference -> contraction of smooth muscle -> peristalsis in the esophagus (autonomic)
60
sphincters
- opening from the esophagus -> lower esophageal sphincter
| - exit of stomach -> pyloric sphincter
61
stomach
- parietal cells secret hydrochloric acid -> denatures proteins and breaks apart extracellular matrix that holds tissues together
- secretes a proenzyme- pepsinogen -> converted to pepsin
- pepsin- cleaves peptide bonds
- pH of 1 or 2
- storage: large distensible organ -> we do not need to eat constantly -> small intestine not overwhelmed with food
- initial chemical digestion of proteins (some lipids via gastric lipase) takes place
- mechanical breakdown of food particles
- absorption of small hydrophobic substance (ethanol) (not main site)
- endocrine organ -> gastin
62
anatomy of the stomach
- lower esophageal sphincter
- fundus
- body
- antrum
- pylorus- connects stomach to duodenum
- pyloric sphincter
- rugae- foldings increase the SA
63
surface of stomach
- epithelium is folding inward in the invaginations -> mucosa
- mucosa forms gastric glands
- smooth muscle layer- submucosa
- three layers of smooth muscle -> myenteric plexus
- contractions mechanically breakdown food
64
gastric acid
hydrochloric acid
65
mucous surface cell and mucous neck cells
- secretes alkaline mucous
- protects stomach from its own acid
- mucous neck cells are located in the neck of the gastric gland
- alkaline comes from bicarbonate
66
parietal cells
- secretes gastric acid (hydrochloric acid)
- in the gastric gland
- washed up into the lumen to denature proteins
- also produces bicarbonate ion (base)
67
chief cells
- produces pepsinogen (zymogen)- inactive enzyme
- released into the lumen and onto the surface
- due to low pH pepsinogen autocatalyzes itself -> forms pepsin (active)
- pepsin- endopepdidase, cleaves peptide bonds
68
G cells
- endocrine cells
- produces gastrin
- gastrin NOT released into lumen -> released into circulation
- interstitial -> circulatory
69
stomach: protein digestion
- acidic environment of stomach (pH 1-2)
- disrupts extracellular matrix that binds cells together
- denatures (unfold) proteins
- creates more surface area on food particles -> more interactions between enzymes and substrates
- kills some microbes (some protection)
70
secretion of hydrochloric acid
- secreted by parietal cells
- H+/K+ ATPase pump in the apical surface (lumen of stomach side)
- not electrogenic (one for one)
- carbonic anhydrase combines water, CO2, and carbonic acid -> H+ and bicarbonate (HCO3-) -> H+ moves across apical surface into lumen
- biocarbonate moves across basolateral membrane (interstitial fluid side) in exchange for Cl -> Cl moves across apical surface into lumen
- H+ and Cl form hydrochloric acid
- bicarbonate moves into the capillaries by bulk flow -> gets incorporated into alkaline mucus
71
stomach acid (HCl)
- secondary and tertiary structures are disrupted by H+ ions
- H+ ions compete with hydrogen bonds -> denature secondary and tertiary structures
- unravels
- after they are denatured now peptide bonds are easier to cleave
- dont usually refold (bc they need chaperones) but ribonucleases can help renature
72
pepsin
- pepsinogen- inactive enzyme -> had 44 additional amino acids that maintain zymogen in an inactive form
- pepsinogen (inactive) -> pepsin (active) after release from chief cells into the lumen of stomach
- activated only where needed
- low pH of lumen causes the catalytic conversion
- HCl causes pepsinogen to unfold and autocatalytically cleave the inhibitory 44 amino acids -> pepsin
- pepsin cleaves pepsinogen to generate more pepsin
73
stomach: gastric juice
- aqueous mixture of pepsin and acid in the stomach lumen
- effective at digesting proteins because:
- acid denatures the proteins, exposing peptide bonds to pepsin
- pepsin is one of few enzymes that is most effective at low pH (gastric lipase also functions optimally at low pH)
74
stomach: protection
- alkaline mucus coats and protects the stomach epithelial cells from pepsin and HCl
- mucus neck/surface cells -> alkaline mucus
- bicarbonate (from parietal cells) is incorporated in the mucus
- mucus- physical barrier
- bicarbonate- chemical barrier that neutralizes acid -> if pepsin where to get to the bicarbonate layer activity would decrease due to higher pH (7)
- epithelial cells constantly sloughed- mitosis generates enough new epithalial cells to replace lining about every 3 days -> sloughed off cells are digested with food
75
GERD
- reflux of gastric juice into the esophagus can cause gastroesophageal reflux
- common after big meal
- acid and pepsin in direct contact with esophagus -> burns
- heart burn
76
peptic ulcer disease
- gastric juice can cause gastric and duodenal ulcers
- mucus defenses are compromised (not enough)
- pepsin and acid come in direct contact with living tissue of stomach
- digests the stomach itself
- common in duodenum (70%) because there is less protection there
77
omeprazol (prilosec)
- drug
- blocks H+/K+ ATPase proton pump
- covalently bonds to cystine residues in the pump -> disables
- parietal cells no longer release acid into the lumen
- raises pH of stomach
- provides time for ulcer to heal itself
78
stomach: mechanical digestion
- contents of stomach are mixed by contractions of smooth muscle in the stomach wall
- mixture of contents is called acidic chyme
- contractions slowly push the acid chyme through the pyloric sphincter into the small intestine
79
small intestine: functions
- major organ of digestion and absorption
- major site of enzymatic hydrolysis of macromolecules of food
- major site for absorption of nutrients (mostly monomers) into blood
- largest part of intestine (6 meters)
- endocrine organ
80
small intestine: nutrient absorption
- occur mainly in jejunum (and ileum)
- 3 levels of organization increase SA (300m^2) and facilitate absorption:
- plicae- large circular folds
- villi- finger like projections
- microvilli- epithelial cells on each villus have microscopic projections
81
anatomy of small intestine
- smooth muscle
- contracts in peristaltic motion
- crypt- glandular evaginations -> exo/endocrine cells
- circular muscle, longitudinal muscle
- peyers patch- lymphoid tissue (immune system)
82
villus
- rich blood supply (many capillary)
- most food is absorbed here
- increase SA
83
lacteals
- part of lymphatic system
| - within the villus
84
goblet cells
secrete mucus on villus
| -mucus for lubrication rather than protection
85
crypts
- have exo/endocrine
- envagination
- most fluid secretion occur here
- stem cells in crypts produce new epithelial cells to replace dead or damaged
- secrete ions and water (exocrine)
86
enterocyte
-transport nutrients and ions
87
microvilli
- make up brush border
| - increase SA
88
duodenum
- 23 cm long, posterior to pyloric sphincter
- acid chyme from stomach is mixed with digestive juice from: pancreas, liver/gallbladder, secretory cells in intestine wall
- chemical digestion
- bile salt- molecule of cholesterol that is conjugated to an amino acid
89
jejunum
- largest portion of small intestine
- 3 meters
- major site of chemical digestion and absorption
90
illeum
- more absorption
| - whats not absorbed by jejunum is absorbed here
91
bile
- contains bile salts, bile pigments, and cholesterol
- -cholesterol (hydrophobic) molecule conjugated into amino acid (hydrophilic) -> ampipathic molecule
- secreted by liver cell; stored in gallbaldder
- released into common bile duct -> into duodenum
- bile salts (cholesterol + amino acid):
- act as detergents -> coat fat droplets and keep them from clumping together (emulsifiers)
- facilitate fat hydrolysis by lipases
92
pancreatic juice
- exocrine pancreas secretes enzymes (zymogens) and bicarbonate
- released into the lumen of duodenom
- acinar cells from exocrine pancreas secrete zymogens and bicarbonate into pancreatic duct -> lumen of small intestine
93
exocrine pancreas
- bicarbonate- neutralizes acidic chyme from stomach into duodenum (raises pH to 7-8)
- peptidases- continue digestion of protein
- nucleases- hydrolyze DNA to RNA
- amylases- continue digestion of carbohydrates
- lipases- digests fats
- all are initially released into pancreatic duct, which joins the common bile duct and empties into duodenum
94
zymogens
- secreted by exocrine pancreas
- inactive as secreted
- become activated in the lumen of duodenum
- enzymes along the brush border called enteropeptidases activate zymogens by activating trypsin by cleaving precursor trypsinogen into trypsin
- trypsin activates zymogens enzymes -> digests foods
95
beta cells of the pancreas release insulin into ducts that lead into the circulatory system
- false
- no ducts in the beta cells
- exocytosis -> capillaries
96
bile salts as detergents and emulsify lipids
- lipid are not soluble -> bc bile salts are amphipathic they can emulsify (solubilize) lipids
- break up lipid droplet into smaller micelles
- hydrophobic side of the bile salt faces the lipid droplet and the hydrophilic side (amino acid) faces aqueous environment
97
lipid micelles
- contain triglycerides, phospholipids, monoglycerides, biglycerides
- lipase and colipase (pancreatic enzymes) breaks down triglycerides into fatty acids and monoglycerides -> these can be absorbed into intestinal cells by diffusion across brush border
- cholesterol is transported into cells by carrier proteins
- triglycerides are resynthesized and combine with cholesterol and proteins in intestinal cells to form chylomicrons
- diffuse by exocytosis on the basolateral surface
- chylomicrons are removed by lymphatic system (too large for capillaries)
98
chylomicrons
- allows us to circulate hydrophobic substances in aqueous environment of lymph and circulatory
- large
- lipoprotein
- phospholipid monolayer around the hydrophobic substances -> hydrophilic transport
- cholesterol + triglycerides + proteins = chylomicrons
- exocytosis through basolateral surface of small intestine cell -> move into lymphatics -> lymph to vena cava -> right side of the heart
99
small intestine: absorption of sugars and amino acids
- sugars and amino acids are absorbed through epithelial cells and into the blood stream
- capillaries in alimentary canal -> hepatic portal vein -> liver (removes any non-nutrient we may have absorbed) -> vena cava -> right atrium
- often secondary active transport, using gradients of Na established by Na/K ATPase pump
100
hepatic portal system
- most substances absorbed by the intestine pass through the liver
- liver serves as a filter that can enzymatically modify and break down many potentially harmful xenobiotic substance before they get into the systemic circulation
- enzymatic products are eliminated from the body in bile
- digestive tract arteries -> capillaries of stomach and intestines -> hepatic portal vein -> liver -> hepatic vein -> vena cava -> right atrium
101
lipids
- bypass the liver
- bc they are too big to move through capillaries through bulk flow
- lyphatics -> vena cava -> heart
102
carbohydrate breakdown
- pancreatic enzymes introduced in the duodenum breakdown polymers
- amylase
- polymers-> disaccharides -> monosaccharides
- monosaccharides are absorbed
- glucose or galactose enters with Na (Na gradient made on basolateral surface -> secondary transport) with SGLT at apical and leaves through GLUT2 at basolateral
- fructose enters on GLUT5 at apical and exits at GLUT2 at basolateral
- glucose is able to diffuse into capillaries by bulk flow -> liver -> vena cava -> heart
103
endopeptidase
- digests internal peptide bonds in the middle
- include pepsin in the stomach
- trypsin and chymotrypsin in small intestine
- cleaves into smaller peptides -> more free ends
104
exopeptidase
- digest terminal peptide bonds to release amino acids -> free amino acids
- free amino acids are what is being absorbed
- some peptides larger than tripeptides can be absorbed by transcytosis
105
absorption of amino acids and peptides
- proteins cleaved by endopeptidase and exopeptidase -> free amino acids
- amino acids cotransport with Na (Na gradient formed on basolateral surface -> secondary transport)
- move across basolateral surface and enter capillaries by bulk flow
- di and tripeptides cotransport with H+
- small peptides are carried intact across the cell by transcytosis
106
absorption of water and solute
- on basolateral surface there is a Na/K ATPase pump -> establishes gradient
- Na transport across the apical surface through sodium channels, symporters with Cl, antiporters with H+, antiporters with HCO3-, and symporters with organic solute (glucose, amino acids)
- water follows solute -> water moves through the paracellular pathway
- water moves from the lumen of small intestine through the intestinal cell into the ECF
107
small intestine has a large capacity for absorbing water
- small intestine absorbs a lot of water (7.5L a day)
| - drinking too much water can cause increased absorption diluting blood volume -> death
108
large intestine (colon)
- connected to small intestine at a T shaped junction
- one arm of the T is a pouch called the cecum
- functions:
- reabsorption of water- most water reabsorption occur in small intestine, excess water in colon can lead to diarrhea, insufficient water in colon can lead to constipation
- microbial digestion and absorption of microbial products
- elimination
109
regulation of digestion by hormones
- stomach secretes gastrin, a peptide hormone
- duodenum secretes two peptide hormones: secretin & cholecystokinin (CCK)
- released basolaterally into circulation
110
gastrin
- gastrin is produced by G cells
- released basolaterally into circulation (hormone from stomach)
- stimuli:
- food (proteins in stomach) and vagus nerve activation
- targets (binds to):
- chief cells -> pepsinogen -> pepsin
- parietal cells -> stomach acid (HCl)
- response:
- increased protein digestion
111
secretin
- released basolaterally into circulation (hormone from duodenum)
- stimuli: low pH in duodenum caused by acidic chyme
- targets: pancreas -> stimulates the secretion of bicarbonate
- response: raises pH duodenum for increased digestion and protects the duodenum from acidic chyme
112
cholecystokinin (CCK)
- released basolaterally into circulation (hormone from duodenum)
- stimuli:
- amino acids and fatty acids in duodenum
- targets:
- pancreas -> stimulates release of digestive enzymes (proteases, lipases, amylase)
- gallbladder -> bile is released into duodenum when gallbladder contracts
- response:
- increased digestion of fats and proteins
113
evolutionary adaptations
- appendix- has lymphoid tissue, houses bacteria that could potentially repopulate our system
- cecum- houses bacteria
- herbivores/omnivores have longer alimentary canals than carnivores, relatively
- long cecum is one ex. (in other animals cecum breaks down cellulose)
- plant materials more difficult to digest than animal cells
- longer tract provides: more time for digestion and more SA for digestion
114
ruminants
- cow
- eats plant -> rumen -> reticulum (backward flow) -> large material goes to oral cavity to be rechewed
- smaller material is passed to the omasum -> abomasum -> intestine
- rumen- large fermentation chamber -> anaerobic breakdown of carbohydrates (cellulose)
- abomasum- digestion
- omasum- absorption
- bacteria is digesting cellulose
115
symbiotic organisms
- microorganisms thrive in fermentation chamber in herbivores
- mircoorganisms provide nutrients
- digest cellulose into monosaccharides
- secrete fatty acid
- provide essential nutrients (vitamins)
- are digested by hosts to provide a direct nutrient source
116
most chemical digestion of carbohydrates occurs in the stomach
- false
- stomach is mostly for proteins
- further digestion of carbohydrates is in the small intestine (duodenum) by amylases
117
chief cells secrete pepsin
- false
- it secretes pepsinogen
- zymogen
118
pepsinogen enzymatically cleaves peptide bonds in ingested (dietary) proteins
- false
| - zymogen -> inactive
119
in response to reduction in pH (caused by acidic chyme), secretin is released into the lumen of the duodenum
- false
| - secretin is a hormone
120
structure of a long bone (femur or humerus)
- bone is living tissue (connective tissue) -> organ
- trabecular bone and compact bone consist of living cells (osteocytes, osteoblasts, and osteoclasts) embedded in a mineralized Ca organic matrix (collagen and hydroxyapatite)
- bone is an organ composed on multiple tissues:
- bone and cartilage tissue
- red marrow and blood (connective tissue)
- blood vessels (endothelial tissue)
- yellow marrow (adipose tissue, a type of connective tissue)
121
osteoblasts
- secrete proteins (collagen and proteoglycan)
- create the matrix of bone
- cells that take calcium from plasma and use it to build bone
- growth and remodeling
122
diaphysis
shaft
123
epiphysis
-ends of the bone
124
metaphysis
-includes the epiphyseal plate and scar
125
epiphyseal plate
- site of bone growth after birth
- growth plate
- made of cartilage from chondrocytes
- linear growth
- after puberty (no more growth hormone) osteoblasts create calcium phosphate crystals (hydroxyapatite) to replace cartilage)
126
trabecular bone
- aka spongy bone
- aka cancellous bone
- where red bone marrow is
- found in epiphyses
- trabeculae- distribute the force placed on the bone -> can remodel
- present prior to puberty and after
127
articulate surface
-forms joint with other bone
128
chondrocytes
- cartilage cells that secrete extracellular matrix scaffold for bone to grow on
- associated with the ends of the bones that form joints (articular surface)
129
osteoclasts
- cells that resorb bone
- these cells remove calcium from bone and deposit it in plasma
- secrete enzymes and acids that deplete the cell matrix
- multinucelated -> result from diffusion of macrophage stem cells
130
osteocytes
- mature, inactive osteoblasts found in bones that have stopped lengthening
- still alive
131
cartilage
- cartilage is a type of connective tissue
- composed of chondrocytes that secrete a large amount of collagen and heavily glycosylated proteins -> proteoglycans
- collagen and proteoglycans makeup extracellular matrix and semi-rigid structural properties characteristic of cartilage
- semi-rigid -> ear
132
bone tissue
- type of connective tissue
- composed of osteoblasts, osteocytes, and osteoclasts
- cells are embedded in extracellular matrix composed mostly of collagen and proteoglycans
- extracellular matrix of bone is rigid due to mineralization with hydroxyapatite (calcium based mineral) -> key difference between cartilage and bone
133
lacunae
-osteoblasts get trapped in here and become osteocytes
134
bone growth
- bones start out as cartilage in fetus
- cartilage replaced by bone
- growth continues at the ends of long bones in epiphyseal plates until end of puberty
- epiphyseal closure occurs when bones stop growing
- bone growth may be restarted after injury
135
development of embryonic cartilage and bone
- step 1- mesenchymal cells differentiate into chondrocytes -> chondrocytes at the center of the growing cartilage model secrete extracellular matrix (proteoglycan and collagen) -> forms a semi-rigid structure -> chondrocytes enlarge and begin to secrete phosphate salts and calcium -> cartilage begins to calcify -> chondrocytes die as the matrix calcifies
- step 2- mesenchymal cells differentiate into osteoblasts -> osteoblasts cover the shaft of the cartilage in a thin layer of bone -> cells in the middle start to undergo apoptosis -> cavity forms
- step 3- blood vessels penetrate the cartilage -> vascularization -> new osteoblasts form a primary ossification center -> mesenchymal cells differentiate into osteoclasts -> breaks down matrix -> forms a marrow cavity new osteoblasts form a primary ossification center
- step 4- bone of the shaft thickens and cavity enlarges -> cartilage near each epiphysis is replaced by shafts of bone
- step 5- blood vessels invade the epiphyses and osteoblasts form secondary centers of ossification at the ends of the bones
136
mesenchymal cells
- immature stem cells
- differentiate into chondrocytes and osteoblasts depending on stage of bone development
- osteoclasts are not formed by mesenchymal cells -> they are derived from macrophage stem cells!
137
growth of epiphyseal plate
- chondrocytes are rapidly proliferating and laying down extracellular matrix at the top of the plate
- extending the bone upwards bc more cells are being added
- osteoblasts are laying down new bone at the other end (trailing end) -> ossified
- this process is driven by growth hormone
138
why doesnt growth just happen at the ends of bones
- bc joints need to be able to fit together
| - this would affect bone/joint function
139
bone remodeling
- for life
- osteoblasts secrete collagen and proteoglycans and calcium and phosphate minerals (hydroxyapatite)
- hydroxyapatite binds to collagen and proteoglycans and form calcified bone matrix (rigid bone)
- osteoclasts secrete acids (hydrochloric) and enzymes -> dissolves, breaks down and solubilizes bone matrix
140
exercise
- affects the balance of osteoblast to osteoclast
- more exercise -> more osteoblast function -> denser bones
- less exercise -> more osteoclast function -> less dense bones
141
calcium balance in body
- input from: diet
- output to: urine (major) or feces (minor)
- regulation by: parathyroid hormone (PTH), calcitriol (vitamin D3), and calcitonin (minor role)
- calcium is absorbed in small intestine
- 99% of Ca in bone
- .9% in cells
- .1% in ECF
- calcium it taken from bones (resivior) and given to cells and ECF -> osteoporosis
- PTH recovers Ca from kidney so its not excreted as urine
142
blood
- connective tissue
- composed of cells, platelets, and fluid extracellular matrix (plasma)
- extracellular matrix is fluid in blood (rigid in bone)
- similar to interstitial fluid except plasma contains many proteins like albumins
- plasma is 92% water weight
143
components of blood
- 42% RBC
- <1% WBC
- 58% plasma
- PLASMA:
- water, proteins, other molecules
- composition varies (ex. hormone levels fluctuate)
- CELLS:
- erythrocytes
- leukocytes
- PLATELETS:
- fragments of megakaryocytes (large cells)
- no nucleus
- have mitochondria, smooth endoplasmic reticulum, and vesicles (granules) filled with cytokines and other signaling molecules
144
white blood cells
- immune function
- 4-11 x 10^3 cells per microliter
- lymphocytes
- monocytes- phagocytes, develop into macrophages and dendritic cells
- neutrophils
- eusinophils
- basophils
- mast cells
- macrophages, dendritic cells, and neutrophils are key cells that can do phagocytosis
145
platelets
- secrete factors
- fragments of megakaryocytes (large cells) -> platelets are not cells they are fragments of cells
- no nucleus
- carry out basic cellular function
- composition varies -> not constant
- composed of water, ions, organic molecules, trace elements, vitamins, gases
- albumins- protein that contributes to plasma colloid osmotic pressure: carriers for various substances
- have mitochondria, smooth endoplasmic reticulum, and vesicles (granules) filled with cytokines and other signaling molecules
146
hematopoiesis
- red blood cell formation
- occur in red bone marrow
- red bone marrow is in the epiphyses
- in children its everywhere
- in adults is mostly just ends of long bones, pelvic gurdle, spinal column, ribs, clavicle, scapula and skull bones
147
yellow bone marrow
- found in diaphysis
| - mostly adipose tissue
148
red bone marrow
- forms in the spaces between the mineralized bone
- contains pluripotent stem cells -> can develop into many but not all cell types
- blood cells develop in red bone marrow in a process called hematopoiesis- the cells then move into circulation
- differentiation- the process of activating a select set of genes to produce gene products found in only a specific cell type
- found everywhere in children
- found in ends of long bones, pelvic gurdle, spinal column, ribs, clavicle, scapula and skull bones for adults
149
pluripotent hematopoietic stem cell
- can become lymphocyte stem cell -> lymphocyte
- can become uncommitted stem cell -> committed progenitor cells -> can become either eosinophil, basophil, monocyte, neutrophil, megakaryocyte (into platelet), or erythrocyte
- refer to diagram in notes
150
red bone marrow continues
- highly vascularized
- consists of blood cells in different stages of development and support tissue (stroma)
- cells move in between endothelial cells into circulation
151
lymphocytes
- involved in specific immune responses
- T cells
- B cells
- natural killer cells
152
monocytes
- large phagocytic cells
| - can differentiate into macrophages (phagocytic) and dendritic cells (phagocytic)
153
neutrophils
-neutral dye, granules, phagocytic
154
eosinophils
-acidic dye, granules phagocyte
155
basophils
basic dye, granules
156
red blood cells
- function- gas transport
- appearance- round, red, biconcave, no nucleus
- count- 4-6 x 10^6 cells per micoliter
157
platelets
- function- blood clotting
- appearance- small fragments of cells
- no nucleus
- have granules
- mitochondria
- smooth endoplasmic reticulum
- count- 1.5-4.5 x 10^5 cells per microliter
- initially they are smooth -> when they are activated they become rough and stick
- become activated when they are needed to clot
158
blood clot (thrombus)
1. vessel constriction- blood loss -> constriction
2. platelets arrive -> platelet adhesion -> platelet activation -> platelet aggregation
3. formation of cross linked fibrin -> stabilizes the clot/platelet plug
4. restriction of the clot forming process to the area of vessel damage -> spreading of clots is lethal!
- note: no physiological mechanism to stop bleeding large arteries -> surgery
159
platelet adhesion, activation, and aggregation
- vessel wall is intact -> no collagen is exposed
- collagen wall of blood vessel is exposed to platelets at site of vessel damage
- platelet receptors in membranes bind to collagen -> activates -> platelets become rough -> platelets release several signaling molecules/factors that activate other platelets -> adhere to each other and the wall of the vessel -> loose platelet plug forms
- collagen acts as ligand
160
coagulation cascade
- overlaps platelets activation
- tissue factor exposed triggers coagulation cascade
- cross linked fibrin -> reinforces platelet plug
- stabilizes platelet plug
- each step is amplification -> fast
- Ca cofactor
161
tissue factor
- exposed tissue factor triggers coagulation cascade
- transmembrane protein (not an enzyme) found in smooth muscle membrane
- normally smooth muscle membrane is protected by endothelial cells
- intact endothelium in tissue factors releases factors that inhibit platelet formation
- during injury factor 7 (zymogen- inactive) comes in contact with tissue factor it activates -> conformation change -> factor 7 becomes enzyme
- factor 7 converts many factor 10's into active factor 10's
- active factor 10 cleaves prothrombin into thrombin
- thrombin cleaves fibrinogen into fibrin monomers
- active factor 13 cross links fibrin with Ca -> cross linked fibrin polymer
162
positive feedback
- active 10 will generate more active 7 -> active 10 is able to generate more active 7
- thrombin will generate more active 9 which converts inactive 10 to active 10
- positive feedbacks forms bursts of active 10
163
conversion of fibrinogen into fibrin, subsequent fibrinolysis
- tissue plasminogen activator (tPA) converts plasminogen (precursor to zymogen) into plasmin
- plasmin- enzyme that breaks down fibrin fragments -> dissolved blood clot
164
tissue plasminogen activator (tPA)
- important drug
- dissolved clot to prevent brain damage
- stroke
165
immunuology
-the study of the physiological defenses by which the body (the host) recognizes "self" from "non-self" (foreign matter)
166
pathogens
microbes that could potentially cause disease
| -some microbe are good
167
abnormal self cells
- cancerous cells-acquired mutations that allow to invade immune system
- virally-infected cells- recognize host cells
- old or dead cells- eliminate dead cells
168
transplanted tissues or organs
-drugs suppress the immune system during transplant
169
first layer of immune defense
- barriers
- physical- skin, mucosae, mucus, and other secretions
- mechanical- flushing mechanisms such as cilia
- chemical- enzymes and antibodies, pH
170
second layer of immune defense
- innate immune response: rapid, nonspecific, no memory, already present
- cells:
- macrophages
- neutrophils
- natural killer (NK) cells
- dendritic cells
- eosinophils
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second layer of immune defense
- innate immune response: rapid, nonspecific, no memory
- cells:
- macrophages
- neutrophils
- natural killer (NK) cells
- dendritic cells
- eosinophils
- Chemicals:
- complement- system of peptides -> cascade
- interferons- peptides that are released from host cells that have become infected
172
third layer
- adaptive immune response: slow, specific, has memory
- cell mediated responses:
- B lymphocytes
- plasma cells
- T lymphocytes
- cytotoxic T cells
- helper T cells
-antibody -mediated responses
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pathogens: viruses
- viruses are not cellular life forms
- viruses replicate inside host cells (ribosomes)
- an infected host cell can release 1000s of viral particles
- immune system must recognize and kill infected host cells
- cytotoxic T lymphocytes are the main defense against viruses that have infected host cells
- viral antigens are displayed via MHC 1 on infected cells
- virus infected host cells release interferons (a peptide)
174
influenza virus
-envelop surrounds nucelic acid
175
antigens
- small peptides
| - displayed on surface of cells
176
interferons
- peptide signaling molecules
- cytokines
- released by virus infected host cells
- signal to neighboring host cells to prevent them from also becoming a virus factory
177
pathogens: bacteria
- are cellular life forms
- replicate rapidly on their own (need nutrients)
- upon infection, replicate outside of host cells, in the hosts tissues
- high mutation rate
- release variety of toxins that kill host cells
- release enzymes that break down host macromolecules -> cells disintegrate
- release peptides that form pore in our cells -> rapid diffusion -> bacteria uses that cells nutrients
- immune system must recognize and eliminate bacterial cells
178
epithelium
- protective barrier of skin and mucous membranes is the bodys first line of defense
- GI tract
- prevents microbes from getting into tissues
179
gladnular secretions
- trap and disable pathogens
- secretions include:
- mucus- catches microbes so it can be spit out or swallowed -> stomach kills microbes with pH
- antibodies
- enzymes
180
stomach acidity
-the low pH of the stomach helps destroy swallows pathogens
181
mechanical removal
- pathogens can be physically removed
- mucociliary escalator- cells that line our airways secrete mucus
- tears- lysozymes in tears
- coughing, sneezing
- GI motility
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phagocytic cells
- dendritic cells
- neutrophils
- macrophages
183
antigen-presenting cells (APCs)
- dendritic cells
- macrophages
- present antigens on surface by way of MAC 2 molecules
184
primary lymphoid tissue
- immune cells develop and mature into primary lymphoid tissue
- where cells are born
- *red bone marrow
- *thymus- where T cells mature
185
lymphatic pathway: pluripotent hematopioetic stem cell
- becomes lymphocyte stem cells
- cells are born in red bone marrow
- in the thymus T lymphocytes mature (T cells)
- B lymphocytes and NK cells develop
186
adaptive immune response
- T cells
| - B cells
187
B lymphocytes
- develop into plasma cells
| - plasma cells produce antibodies
188
monocytes
- develop into macrophage
| - dendritic cells
189
mast cells
- packed with granules that contain histamine
| - histamine causes inflammation
190
thymus gland
- in thoracic cavity beneath the sternum and above heart
- important for development of T cells
- eliminates T cells that recognize "self" as foreign
- when it fails to eliminate T cells that recognize "self" as foreign -> autoimmune disease (B cells persist -> type 1 diabetes)
- produces peptides: thymosin, thymopoietin, thymulin
191
secondary lymphoid tissue
- immune cells interact and response to pathogens in secondary lymphoid tissue
- located in places where they can intercept pathogens to keep them from entering general circulation
- encapsulated lymphoid tissue:
- spleen
- lymph nodes
- diffuse lymphoid tissues:
- GALT (gut-associated lymphoid tissue)
- tonsils
192
spleen
- has macrophages that engulf foreign particles within circulation
- removes old or dead RBC
- secondary lymphoid tissue
193
lymph nodes
- throughout body
- during injury bacteria enters interstitial fluid -> swept into vesicles
- lymph nodes intercept these pathogens with macrophages
- secondary lymphoid tissue
194
GALT (gut-associated lymphoid tissue) and tonsils
-diffuse lymphoid tissue (secondary) -> adaptive immune system
-not encapsulated
-B cells and plasma cells (producing anitbodies) -> recognize foreign invaders
GALT:
-largest immune organ
-intestine
-bc intestine has thin surface for absorption it also allows for bacteria to diffuse in
195
innate immune defenses
- several strategies used to eliminate microbes or prevent them from reproducing or spreading within body
1. phagocytes
2. natural killer (NK) cells
3. antimicrobial proteins- complement & interferons
4. inflammation
5. fever
196
natural killer cells
- release molecules that will kill an infected host cells
- NK cells get very close to infected host cell and release chemicals to kill
- induces programmed cell death
- tumor cells
- virus infected cells
197
how do phagocytic cells know which cells are foreign?
- they express pattern recognition receptors (PRRs) on their cell membranes
- PRRs specifically bind to pathogen-associated molecular patterns (PAMPs) -> classes of molecules that are the surface of the bacteria (ligand)
- binding leads to phagocytosis and destruction of the microbe
198
PAMPs and PRRs
- PAMPs (pathogen-associated molecular patterns) are conserved molecular structures (molecular motifs) produced by microorganisms, but not by host cells
- PAMPs can be though of as a molecular signature pattern for pathogens
- ex. of PAMP is lipopolysaccharide (LPS)- component of cell walls of many bacteria
- represent potential targets for the immune systems of host animals
- recognized by PRRs (pattern recognition receptors on host cells (phagocytes)
- PRRs evolved as a mechanisms to rapidly detect foreign invaders based on the presence of conserved molecular motifs
199
mechanism for recognition for NK cells
- normal host cells (with a nucleus) have major histocompatibility complex 1 (MHC 1) molecules on their surface; NKCs are blocked from attacking these cells -> dominant inhibition on
- some viruses and tumors cause MHC 1 proteins to be down regulated -> infected host cells and tumor cells lack MHC 1 molecules and become targets for NK cells
- perforin forms a channel in the target cell membrane -> granzyme initiate apoptosis (programmed cell death)
- respond within first hour of an infection
- release cytokines that activate other parts of immune system
200
MHC 1
-major histocompatibility class 1
-all cells that have a nucleus express MHC 1
-
201
cytokine
- a family of peptide messengers released by one cell that affect the growth and activity of another cell
- cytokines are made on demand, unlike peptide hormones, which are made in advance and stored in vesicles (insulin)
- act locally
- peptide signaling molecule
202
antimicrobial proteins
- complement proteins
- interferons
- control infection by:
- directly killing microbial cells
- inducing apoptosis in infected cells
- aiding the adaptive immune system
203
antimicrobial proteins: complement
- a family of about 30 proteins that are activated in a cascade
- made in advance
- initially secreted in inactive forms
- initiation of the activation cascade can occur by several mechanisms -> classical pathway
- classical pathway is initiated when complement protein C1 bind to an antibody-antigen complex (an antibody bound to surface of a bacterium)
- central complement protein is called C3
- function of complement proteins:
- acts as Opsonins
- assemble into membrane attack complexes (MACs) -> pores
- act as chemotaxins (attract other immune cells)
- activate mast cells
204
complement cascade- classical pathway
- bacterium invades tissues -> into circulatory system
- bacterium is coated in antibody
- C1 binds to the antibodies -> activates C1
- activation of hydrolase (an enzyme) that cleaves C3 protein into C3a and C3b
- C3a- binds to mast cells which releases histamine -> causes inflammation
- C3b- function as Opsonin
205
C3a
- binds to mast cells to release histamine
- histamine causes inflammation
- local capillaries dilate and become more permeable to cells and fluid -> leakage and fluid and cells into interstitial fluid
206
Opsonin
- chemicals (usually proteins) that bind to a microbe and promote phagocytosis
- bacteria coated with antibodies -> antibody is acting as opsonin
- tags bacteria
- ex. C3b
- C3b is not an antibody itself
207
bacterial hiding antibodies
- bacteria will hide antibodies behind a carbohydrate coat
- this is where C3b comes into play
- C3b is still able to be recognized by phagocytic cells
208
C3b
- functions as an opsonin
- activates other complement proteins -> C9
- C9- forms an aqueous pore in cell membrane
209
complement cascade: Membrane attack complex (MAC)
- a group of complement proteins (C9 and others) insert into the bacterial cell wall and form pores that cause cell lysis
- C9 and other complement proteins insert themselves into membranes of pathogen -> create pores
- water and ions enter the pathogen though pores -> pathogen swells and lyses
- macrophages clean the debris
210
antimicrobial proteins: interferons
- proteins released by one virally infected host cell that prevent viral replication in neighboring host cells (interferons interfere with viral replication)
- virus enters host cell -> synthesis of viral nucleic acid & proteins -> assembly of new viral particles -> release of viral particles -> viral invasion of another host cell -> repeat
- group of about 20 cytokines that are produced by host cells
- primarily used against virus but also against other pathogens and host cells that are tumorigenic
- can also activate NKCs and macrophages
- used for drug therapy
211
interferon mechanism
- interferons are produced by host cells
- triggered by viral DNA
- turn on host genes that express interferons in response to viral DNA
- interferons are released by exocytosis
- bind to cell surface receptor -> signaling cascade -> influences gene expression
- proteins that are expressed interfere with viral replication by shutting down translation
- prevents neighboring cells from doing viral replication
212
interferon drug therapy
- interferons beta-1a and beta-1b are used in a management of multiple sclerosis -> autoimmune disorder characterized by loss of myelin in neurons of brain and spinal cord
- interferon therapy is also used along with other drugs as treatment for certain cancers
213
inflammation
- local redness, heat, swelling, and pain
- chemical signals cause capillaries to become more permeable to:
- plasma proteins -> causes water to move into tissues down osmotic gradient (swelling)
- phagocytic cells-> neutrophils and monocytes leave the capillaries and enter the tissue in a process called extravasation (aka diapedesis)
- major signal is histamine released from mast cells
214
inflammation ex
- splinter -> brings in bacteria
- resident cells (cells already present in the tissue) like macrophages and mast cells work
- mast cell release histamine which binds to receptors on endothelial cells of capillaries -> increase permeability
- allows other immune cells to diffuse through and join the fight -> extravasation
- mast cells also secrete chemotaxins which also attracts cells to join the fight
215
overall reaction
- bacteria enters ECF (interstitial fluid)
- complement proteins become activated as bacteria is coated -> complement cascade
- C3a activates mast cells which secrete histamine which increases inflammation -> additional cells help fight (extravasation)
- phagocytes eat up debris
216
inflammation: mast cells and histamine
- inflammation is a component of normal immune response to invading pathogens
- allergy is an inappropriate inflammatory response to nonpathogenic antigen such as pollen
- initial immune steps that occur during the first exposure to an allergen are equivalent to the normal primary immune response to an antigen
- after initial exposure, antibodies are generated against the allergen and bind to surface of mast cells
- exposure after this results in an exaggerated inflammatory response characterized by the excessive release of histamine
- drugs known as antihistamines block g protein receptors for histamine and help relieve some symptoms of allergic attack (histamine H1 receptor blockers)
- normal immune pathway put into hyperdrive
217
overall review
- breach in the barrier -> bacteria enters ECF
- replication of bacteria
- compliment proteins are activated as bacteria is coated with antibodies (first line of defense) -> compliment C1 binds -> active C3a -> mast cells secrete chemotaxins and histamine -> increases permeability and attracts additional cells to be recruited at the site (extravasation)
- macrophages engulf bacteria directly
- opsonins (C3B protein) are created and coat the bacteria -> phagocytic cells recognize -> engulf
218
fever: pyrogens
- exogenous and endogenous
- endogenous ex.- interleukin IL-1 (IL-1), *IL-6, and tumor necrosis factor (TNF)
- exogenous ex.- components of the cell walls of bacteria (*lipopolysaccharide)
- exogenous pyrogens can stimulate endogenous pyrogen production, or may act directly on the hypothalamus
- initially act on a specific region of the anterior hypothalamus that lacks a blood brain barrier -> leads to synthesis of prostaglandin E2
- pathogens replicate optimally at temperatures below 37C -> this is why fever inhibits reproduction (some immune cells work better at higher temp too)
- fever can be associated with an increase in innate immune activity (phagocytosis) and increased microbial destruction/elimination
- drugs such as aspirin reduce fever by blocking the production of prostaglandins
219
prostaglandin E2
- lipid signaling molecule which acts in the pre-optic nucleus of the hypothalamus to increase the temperature set point
- synthesized after pyrogens act on specific region of anterior hypothalamus
220
both macrophages and neutrophils are components of the innate immune response to a pathogen
true
221
summary: host response to pathogen
- lesion -> bacteria enters -> replicates
- resident cells (macrophages & mast cells) release pro-inflammatory chemical signals (histamine)
- histamine binds to receptors on endothelial cells -> capillary wall becomes more permeable -> more resident cells are recruited -> swelling -> increases blood flow to the site (red color) -> mast cells release more histamine
- monocytes/neutrophils are joining the fight by engulfing
- scar tissue and barriers are forming to prevent further bacteria
- ALL bacteria must be engulfed
222
inflammation
local redness, swelling, heat, pain due to increased capillary permeability to plasma proteins and movement of water from plasma to the interstitial compartment
223
pus
- yellowish
- viscous fluid
- forms as cells in the area (neutrophils) begin to die
- plasma membrane of neutrophils breaks down and forms pus
224
necrotizing fasciitis
- flesh eating bacteria
- antibiotics dont work
- failure of innate immune system
- vibrio vulnificus
- bacteria is releasing enzymes and peptides that form pores in the cells of his skin/tissues
- breaks down collagen and proteoglycan that forms the extracellular matrix
- cells lyse and burst
- IV drugs dont work bc the bacteria is breaking down the RBCs (drugs cant work bc they arent properly circulating in the blood)
- rapid
- not enough immune cells were recruited to the site to combat the bacteria
225
antibacterial drugs
- in the past bacterial infections were way more deadly
- now that we have medication death rates have dropped
- alexander fleming introduced these drugs in 1928
- derived through microbes
- bacteria can adapt to these drugs
226
antigen presenting cells (APCs)
- dendritic cells
- macrophages
- present foreign antigens to the adaptive immune system
227
antibody mediated response
humoral response
- refers to soluble factors (antibodies) that are present in blood plasma
- specific recognition
228
2 divisions of the adaptive immune system
- cell mediated immunity: immune cells use contact with pathogens/abnormal cells and subsequent contact-dependent signaling processes to neutralize them (t and b cells)
- humoral immunity: antibody mediated responses
229
Step 1. encounter and recognize: adaptive immune
- B cells
- Helper T (TH) cells
- cytotoxic T (TC) cells
- encounter and recognize antigens (foreign molecule)
- antigens are acting as ligands
- bind with specific receptor proteins
230
antigen
- small foreign fragment of a protein, lipid or carbohydrate that triggers an immune response (usually protein bc of diversity)
- only a small sequence needs to recognized
- each adaptive immune cells can only recognize ONE potential antigen
- healthy animals do not gave adaptive immune cells specific to self antigens (leads to autoimmune diseases)
- many adaptive immune cells will never encounter an antigen they recognize (most arnt used)
- have specific receptors that recognize foreign molecules
- specific!
- ex. 8-16 amino acids in a folded protein, thousands of potential antigens in a given protein, millions in a microbial cell
231
PRR vs antigens
- PRR recognize broad molecular patterns/motifs
| - antigens recognize specific foreign molecules
232
Step 2. activate: adaptive immune
- T and B cells (lymphocytes) become activated after interacting with an antigen
- lymphocytes respond to contact-dependent signaling by proliferating and changing patterns of gene expression
- activated B cells proliferate -> become specialized to secrete antibodies
- activated helper T cells release cytokines in order to help the overall response
233
antibodies
- soluble form of B cell receptors
- specific to antigen
- act as opsonins
- trigger mast cell degranulation
- activate complement
- activate B cells
- stable and can circulate for very long in the plasma
- do not have enzymatic activity
- neutralize toxins
234
Step 3. Attack: adaptive immune
- lymphocytes kill microbes or abnormal cells
- cytotoxic T cells directly attack cells with exposed foreign antigens on their surface (virus and cancer cells)
- antibodies that are produced by B cells are attacking by clumping antigens, inactivating bacterial toxins, acting as opsonins, triggering mast cell degranulation, activating compliment cascades, activating B cells
235
lymphocytes
-B and T cells
236
Step 4. Remember: adaptive immune
- second response to a particular antigen is faster and more robust than the first response
- memory
- long term memory cells
- 1st expose may take up to a week
- 2nd exposure is rapid
237
B cell receptors (BCRs)
- expressed on surface of B cells
- encoded by two genes that undergo rearrangement during development
- huge amount of BCRs (10 billion)
- secreted B cell receptors are antibodies
- can bind soluble proteins directly (toxins)
- consists of two identical heavy chains and two identical light chains linked by several disulfide bridges (stable)
- not an antibody bc it has a transmembrane domain (membrane anchored antibody)
- transmembrane and cytosolic domains initiate signaling cascade in response to antigen binding
- alternative splicing of the initial RNA molecule splices out the transmembrane domain -> creates an antibody
- bivalent- two antigen binding sites per antibody
- *specificity stems from gene rearrangment in the variable region
- constant regions are constant within a class
238
T cell receptors (TCRs)
- expressed on surface of T cells
- encoded by two genes that undergo rearrangement during development
- huge amount of BCRs (10 billion)
239
B cell activation
- antigen binds to B cell receptor
- high specificity and high affinity interaction
- 2nd messenger signaling pathways lead to changes in gene expression and other cellular processes
- clonal expansion occurs- B cell divides to produce multiple identical cells with the same BCR (proliferation (OD MITOSIS))
- some B cells become memory cells while others become plasma cells
240
memory cells
- long lived
| - respond rapidly to nexr exposure to the same antigen
241
plasma cells
- short lived
- each plasma cell secretes antibodies that recognize a specific antigen
- differentiated B cells that secrete antibodies
- antibodies are just soluble forms of the B cell receptor
- a lot of endoplasmic reticulum present on these cells to ramp up production of antibodies (proteins)
242
clonal expansion
B cell divides to produce multiple identical cells with the same BCR
- proliferation
- mitosis rapid
- amplification
243
B cells attack with antibodies
Antibody functions:
1. antigen clumping- two bacteria become linked together making it easier to engulfed by a macrophage
2. inactivation of bacterial toxins- simple binding to toxins can disable/neutralize them
3. act as opsonins to tag antigens for phagocytosis- encapsulated bacteria is coated with antibodies which bind to phagocyte receptors (recognition) triggering phagocytosis
4. trigger degranulation of mast cells- binding of pathogens releases granules which are packed with histamine -> kills pathogen by lysing
5. activates compliment cascades- signals mast cells to degranulate
6. activate B lymphocytes- proliferation of plasma and memory cells -> secretion of antibody
244
T cell receptors TCRs
- consists of one alpha chain and one beta chain linked by a disulfide bridge
- monovalent! -> one antigen binding cells
- two chains
- variable region for gene rearangement
- cannot bind soluble molecules directly (needs help) -> coreceptors
245
T cell-antigen interactions
- T cell interactions require:
- antigen specific for a T cells TCR
- correct MHC (Class 1 or 2)
- other membrane proteins (CD8 or CD4) -> coreceptors
- these extra proteins and helpers avoid T cells from self reactive -> safe guard
246
antigen presentation
- foreign proteins are digested inside a host cell
- resulting peptide fragments (antigens) are displayed on the surface of the host cell by host membrane proteins called major histocompatibility complex proteins (MHCs)
- process called antigen presentation
- MHC proteins are essential for adaptive immune system to recognize foreign molecules
- MHC proteins are subdivided into two groups: class 1 and class 2
247
Class 1 MHC
- expressed on the surface of all nucleated cells (bc all nucleated cells have the potential to become a viral factory or can have mutation)
- interacts with cytotoxic T cells
- requires CD8 co-receptor on cytotoxic T cells (helps with specificity of targeting)
- causes destruction of infected or abnormal self cells
- mistakes in this process can be very bad
248
class 2 MHC
- expressed on the surface of antigen presenting cells (macrophages, dendritic cells, and B cells)
- interacts with helper T cells
- requires CD4 co-receptor on helper T cells
- causes enhancement of both B cell and cytotoxic T cell activity
249
how are viral host cells being recognized as bad
- viral proteins are being made
- host enzymes break it down into viral protein fragments (antigens)
- these associate with MHC class 1
- undergo exocytosis and are being displayed on the surface
- cytotoxic T cell comes and recognizes this foreign peptide
- coreceptor CD8 interacts with MHC1 -> forms a tight junction that is super specific
- protein-protein interaction
- cell releases perforin and granzymes that kill the host cell
250
antigen-presenting cells APCs
- bridge between the innate and adaptive immune response -> macrophages (innate) are attracting adaptive immune (helper t cell)
- macrophages, dendritic cells, and B cells are primary APCs
- phagocytic cells that engulf pathogens and enzymatically break down the pathogens proteins to small peptide fragments (antigens) (no reason to kill the host cell)
- antigens are displayed on the surface of the APC via MHC class 2 receptors
- helper T cells interact with APCs that display (or present) antigen via MHC2 receptors
- CD4 co receptor binds to MHC class 2 verifies the interaction
- binding activates the T cell inducing it to secrete cytokines such as interleukin 2 which stimulates other immune cells -> cause them to proliferate and differentiate
251
b cells
phagocytic
252
class 1 MHC molecules are present on the surface of dendritic cells but not mast cells
false
- this is true for class 2
- class 1 can be found on dendritic and mast cells
- class 1 MHC molecules are present on the surface on dendritic cells, but not RBCs (no nucleus) -> true
253
adaptive immune response to pathogen include cell mediated immunity and humoral immunity
true
254
T cell activation
- antigen is presented to T cell on an MHC
- antigen binds to T cell receptor -> high specificity and affinity interaction between MHC, antigen, TCR, and co receptors
- 2nd messenger signaling pathways lead to changes in gene expression and other cellular processes
- clonal expansion- t cell divides to produce multiple identical cells with the same TCR
- cytokine production- t cells secrete cytokines that activate other innate and adaptive immune cells -> interleukin-1, interluekin-2, and tumor necrosis factor (TNF)
255
interluekin-2
- secreted by helper T cells in response to binding to class 2 MHC
- stimulates other immune cells and cause them to proliferate
- ex. increased proliferation of B cells -> differentiation -> plasma (antibodies) and memory cells
256
MHC Class 1 and 2 work together
- virus infected host -> displays viral peptides on surface -> class 1 MHC -> cytotoxic T cell recognizes
- macrophage engulfs virus -> displays virus and MHC class 2 -> helper t cell binds -> secretes cytokines (interleukin-2)
- interluekin-2 binds to receptors on the cytotoxic T cell and causes clonal expansion -> proliferation of cytotoxic t cells kills infected/abnormal host cells
257
attack: cytotoxic t cells
- virus infected host cells
- display virus on surface
- CD8 co receptor
- class MHC 1
- cytotoxic T cell recognizes and secretes perforin and granzymes (within same granule vesicle)
258
perforin
- peptide
- initially inactive
- in presence of calcium it will form a pore in the membrane of host cell
- does not exist free in the plasma
- cytotoxic cell is so close to the host cell the distance is short
- causes unregulated flux of water, ions, small molecules, and enzymes -> swell
- granzymes can enter through the pores -> cell death
- produced by cytotoxic T cells (and NK cells) and is stored in inactive form in the same granules as granzymes
259
granzymes
- proteases (enzymes that break down proteins)
- released by cytotoxic T cells (an NK cells) and stored in cytoplasmic granules (secretory vesicles)
- enters host cells through pores made by perforin
- initiate cell death pathways in host cell
- controlled cell death
- granzyme b initiates by activating caspases (enzymes that when activated control cell death)
- programmed cell death is important bc lysing it would release so much dangerous debris -> collateral damage
260
necrosis
- uncontrolled
| - can cause collateral damage to surrounding cells
261
adaptive immunity memory
- primary immune response makes memory B cells, helper T cells and cytotoxic T cells that can persist for decades
- subsequent exposure to an antigen causes a faster and more robust adaptive immune response
- takes about 5 days for the body to even start making antibodies after first exposure
- antibodies peak at 2 weeks
- 2nd exposure sees antibodies right away exponentially at much higher levels
262
vaccines: primary immune response
- contain weakened or dead microbes or mixtures of molecules isolated from a microbe (lots of antigens)
- microbes grown in a large quantities in cells or eggs (viruses_ or in vats (bacteria)
- often contains adjuvants: immune response enhancing molecules (sometimes PAMPs)
- cause a primary immune response, usually with little or no symptoms of microbial disease
- no replication bc dead
- often cause inflammatory response and fever
263
immunosuppressants
- cortisone, azathioprine
| - *cyclosporine- isolated from a fungus found in a soil sample
264
acute rejections
- occurs after the first few months of transplant
- mediated by T cells and B cells
- can usually be prevented with immunosuppressants
265
cyclosporine
- blocks the expression of the gene that encodes interleukin-2 in T cells
- in helper t cells ^
- shows importance of interleukin-2 and helper t cells
266
risks and limitation of immunosuppressants
- infection
- tumor formation, especially lymphomas
- not a cure (must be taken for life)
- reactivation of latent infection (TB)
267
leading cause of death in america
-heart disease
268
Heart disease: atherosclerosis in a coronary artery
- caused by lack of exercise, poor diet
- occlusion
- build up of LDL cholesterol in artery of heart
- blocks hearts blood supply
- lack of blood flow causes ischemia- insufficient blood supply to a tissue -> tissues may die or have low function
- waste products are not being removed
269
major risk factors for heart disease
- *high blood cholesterol (LDL cholesterol)
- high blood pressure (hypertension)
- diabetes
- being overweight
- being physically inactive
- smoking
- having a family history of heart disease
270
cholecystokinin is a peptide hormone produced by cells of the stomach
- false
- produced by the duodenum (intestine) not stomach
- CCK -> gallbladder -> smooth muscle contraction of gallbladder -> introduced bile into bile duct
- CCK also initiates protein release in pancreas
271
bile salts
- from liver
- detergents
- ampipathic molecule
- emulsifies fat droplets into micelles by coating them
272
pancreatic lipase and colipase
- break down triglycerides into monoglycerides and free fatty acids
- monoglycerides and free fatty acids move out of micelles and into intestinal cells by diffusion (small enough)
- cholesterol is transported into cells by carrier protein
- triglycerides are resynthesized and combined with cholesterol and proteins in the intestinal cells to form chylomicrons
- chylomicrons are removed by the lymphatic system
273
chylomicrons
- efficient way of transporting lipids in aqueous environment
- triglycerides are resynthesized and combined with cholesterol and proteins to form chylomicrons
- triglycerides are in the middle, phosphate head groups on outside -> efficient for transporting hydrophobic molecules
- these chylomicrons are removed (exocytosis) by lymphatics (too big)
274
lymphatics
- chylomicrons that enter the lymphatic system are bypassing the liver
- go to the right side of the heart and back into systemic circulation
- it eventually ends up back in the liver where it repackages the chylomicrons as LDL cholesterol particles
- increased pizza -> increased lipids -> higher your LDL cholesterol
275
Low density lipoprotein (LDL) particle
- triglycerides and cholesterol are transported in plasma as large, macromolecular complexes of lipid and protein known as lipoprotein particles
- 45% cholesterol
- 25% proteins (apolipoprotein B100 binds to lipids)
- 21% phospholipids
- 9% triglycerides
- major risk factor for atherosclerosis
276
development of artherosclerosis
- LDL cholesterol accumulates in the wall of the artery
- macrophages ingest cholesterol and become foam cells in the wall of the artery (innate)
- over long period of time (decades) plaques form
277
heart failure
-plaques and blocks limit the amount of blood flow
-heart adapts to the changes by enlarging
-walls become thinner and weaker (especially left ventricle) due to enlarge (cant pump out CO)
-
278
pulmonary edema
-accumulation of LDL cholesterol in the walls of the left epicardial artery -> occlusion
-excess fluid accumulation in the lung tissues and air spaces, including the alveoli
-output from left ventricle is declining due to weakened heart muscle, right ventricle keeps pumping -> fluid backs up in the lungs -
> difficulty breathing
-bc left is enlarged they are pumping different volumes of blood (5 liters pumped on right side and only 2 pumped out)
-the extra 3 liters are pushed out into circulation at the level of pulmonary capillaries -> into lung interstitial environment (fused basement membrane) -> bc this layer in enlarging the diffusion distance is increasing -> less efficient diffusion of gases
-stiff lungs due to increased fluid as well
-difficulty breathing
279
- heart failure -> enlarged heart -> weak and thin walls -> CO drops -> MAP initially declines from 93 to 85 -> person feels light headed and lies down
- with a MAP of 85 (drop in MAP) the kidneys will continue filtering blood at a normal rate (180L/day)
-true
| -
280
- heart failure -> enlarged heart -> weak and thin walls -> CO drops -> MAP initially declines from 93 to 85 -> person feels light headed and lies down
- with a MAP of 85 (drop in MAP) the levels of renin in the blood will increase significantly
-false
281
- heart failure -> enlarged heart -> weak and thin walls -> CO drops -> MAP initially declines from 93 to 85 -> person feels light headed and lies down
- with MAP= 85 autoregulatory mechanisms would be sufficient to maintain a nearly constant GFR
- true
- if your using autoregulation to maintain GFR you dont need renin
- myogenic -> reduced stretch -> relaxes -> increased flow an GFR
- tubuloglomerular feedback -> reduced flow -> reduced paracrine factors -> relax -> increase flow and GFR
- true for MAP of 80-180
282
a normal health person is lying down and stands up suddenly. how person is vertical and heart must work against gravity to pump blood around circulatory system
-cardiac output falls from 5 to 3 -> the baroreceptor reflex will be initiated
-true
283
a normal health person is lying down and stands up suddenly. how person is vertical and heart must work against gravity to pump blood around circulatory system
- cardiac output falls from 5 to 3
- sympathetic outflow will increase
- heart rate and force of contraction will increase, leading to an increase in cardiac output
- peripheral vascular resistance increases, due to vasoconstriction in vascular beds such as the skin and gastrointestinal tract
- true
- true
- true
284
a person with heart failure stands up suddenly. now person is ventricle and heart must work against gravity to pump blood around circulatory system
- cardiac output falls from 5 to 2
- with MAP 70, autoregulatory mechanisms will maintain GFR at 180 L/day
- false
- false because BP below 80 or above 180 is not controlled by autoregulatory mechanisms
- GFR will drop
285
a person with heart failure stands up suddenly. now person is ventricle and heart must work against gravity to pump blood around circulatory system
- cardiac output falls from 5 to 2
- with MAP 70, levels of circulating renin will increase
- true
- MAP below 80 renin increases
- weakened heart -> MAP falls to 70 -> RAAS initiated -> different paracrine factors are released (prostaglandins) due to the dramatic drop in MAP -> act on granular cells -> release renin
286
renin is a peptide hormone
- false
- its an enzyme
- function in a pathway that produces a hormone
287
vasopressin is a peptide hormone that is synthesized in the posterior pituitary
- false
- vasopressin is synthesized in the hypothalamus
- released at the level of the posterior pituitary
288
urine volume in heart failure patient decreases and blood volume increases
- angiotensin 2 increases vasopressin and aldosterone release
- vasopressin -> increase recovery of water
- aldosterone -> increase sodium recovery
- overall this is absorbing more water which increases blood volume and decreases urine
289
nitroglycerin and furosemide (lasix)
- nitroglycerin-given when difficulty breathing, goes into circulation, releases nitric oxide, vasodilator
- furosemide-blocks ion uptake in the ascending loop of henle, increases urine volume by blocking reabsorption
- blood volume decreases a little with increase in urine volume -> water is drawn from extracellular compartment (lung tissue) to maintain blood volume -> lungs clear of excess fluid -> person can breathe again
290
heart failure development
-behavioral + genetic factors -> high LDL cholesterol -> risk of artherosclerosis -> over time -> coronary artery disease -> weakened LV heart muscle -> pulmonary edema -> difficulty breathing -> 911 -> furosemide and nitroglycerin -> increase in urine and vasodilation -> decreased workload on the heart -> lungs clear of fluid
291
plaques
- overtime the increase LDL cholesterol continues to accumulate
- if the plaque ruptures -> VERY BAD!
- rupture exposes tissue factor and collagen to the lumen of the blood vessel -> creates a clot -> blocks the artery -> cardio myocytes die -> lethal
292
tissue factor binds to receptors on platelets
- false
| - tissue factor binds to tissue factor 7 -> initiates clotting cascade
293
collagen is an extracellular matric protein that can function as a ligand and activate platelets
-true
294
clot
-platelet plug + fibrin net -> stable
