Biology Flashcards
Insulin
Favors the transport of glucose into organs as well as the storage of excess glucose when blood glucose concentrations are high
Glucagon
Triggers the release of sugar stores and raises blood glucose concentration
Type 1 Diabetes Mellitus
- Autoimmune disease in which insulin producing cells (beta cells) in the islets of Langerhans are destroyed
- Requires regular injections of insulin to prevent hyperglycemia and to permit entry of glucose into cells
Type 2 Diabetes
Caused by end-organ sensitivity to insulin; partially inherited and due to environmental factors (high carb diets and obesity)
Hormones
Signaling molecules that are secreted directly into the bloodstream to travel to a distant target tissue. At that tissue hormones bind to receptors inducing a change in gene expression or cellular functioning
Peptide Hormones
- Range in size from quite small (ADH) to relatively large (insulin)
- Derived from larger precursor polypeptides that are cleaved during posttranslational modification. These smaller units are taken to Golgi for further modifications that activate the hormone and direct it to correct location. Released by exocytosis after being packaged in vesicles
- Charged, and cannot pass through plasma membrane, they bind to an extracellula receptor
- Peptide hormone is considered the first messenger and it binds to receptor and triggers transmission of a second signal called the second messenger.
- Type of receptor determines what happens
Signaling Cascade
The connection between the hormone at the surface and the effect brought about by second messengers within the cell. At each step there is a possibility of amplification
Ex: One hormone molecule may bind to multiple receptors before it is degraded. Also, each receptor may activate multiple enzymes each of which will trigger the production of large quantities of second messengers
Second Messenger Examples
Cyclic Adenosine Monophosphate (cAMP), Inositol Triphosphate (IP3) and calcium
Activation of a G protein coupled recepto
Binding of a peptide hormone triggers the receptor to either activate or inactivate an enzyme called adenylate cyclase raising or lowering the levels of cAMP. cAMP can bind to intracellular targets such as protein kinase A, which phosphorylates transcription factors like cAMP response element binding protein (CREB) to exert the hormone’s ultimate effect
Effects of Peptide Hormones
Usually rapid but short lived because these hormones act through transient second messenger systems. It is quicker to turn them on and off, compared with steroid hormones but their effects do not last without relatively constant stimulation.
Peptides are generally water soluble so they can travel freely in the bloodstream and do not require carriers
Steroid Hormones
- Derived from cholesterol and are produced primarily by gonads and adrenal cortex
- Derived from non polar molecule so they can easily cross the cell membrane
- Receptors are usually intracellular (in cytosol) or intranuclear
- Upon binding to receptor, steroid hormone-receptor complexes undergo conformational change
- receptor can then bind to DNA resulting in either increased or decreased transcription of particular genes depending on identity of hormone
Effects of steroid hormones
Slower but longer lived than peptides because steroid hormones cause alterations in the amount of mRNA and protein present in a cell by direct action on DNA
Steroid hormones are not water soluble and thus must be carried by proteins in bloodstream to travel around the body. Some of these proteins are very specific and carry only one hormone while other proteins are non specific. Hormones are generally inactive while attached to a carrier protein and must disassociate to function
Dimerization
common form of conformational change which is pairing of two receptor-hormone complexes
Amino acid derivative hormones
- Less common
- Hormones are derived from one or two amino acids usually with a few additional modifications
- Ex: Thyroid hormones are made from tyrosine with the addition of several iodine atoms
- Chemistry of this family of hormones is less predictable
- Catecholamines (epinephrine and norepinephrine) bind to G protein couples receptors while the thyroid hormones bind intracellularly
Direct hormones
-Secreted and act directly on a target tissue
-Ex: insulin released by the pancreas causes increased uptake of glucose by muscles
Other hormones such as tropic hormones require an intermediary to act
Gonadotropin releasing hormone
Stimulates the release of LH and FSH. LH then acts on the gonads to stimulate testosterone production in the male and estrogen production in female. GnRH and LH do not cause direct changes in physiology of muscle, bone, and hair follicles; rather they stimulate the production of another hormone by another endocrine gland that acts on these target tissues
Hypothalamus
Regulates the pituitary gland through tropic hormones
- Located in forebrain above pituitary gland and below thalamus
- Because the pituitary and hypothalamus are close the hypothalamus controls the pituitary through paracrine release of hormones into a portal system that connects two organs
Suprachiasmatic nucleus
receives some of the light input from retinae and helps to control sleep-wake cycles
Negative Feedback
Occurs when a hormone (or product) later in the pathway inhibits hormones (or enzymes) earlier in the pathway. This type of feedback maintains homeostasis and prevents wasted energy by restricting production of substances that are already present in sufficient quantities
Hypothalamus Interactions with the Anterior Pituitary
- Hypothalamus secretes compounds into the hypophyseal portal system which is a blood vessel system
- Hormones released from hypothalamus travel to anterior pituitary by traveling down pituitary stalk and binding to receptrs in AP stimulating release of other hormones
Hormone examples from Hypothalamus and AP
Gonadotropin releasing hormone –> FSH and LH
Growth hormone releasing hormone –> GH
Thyroid releasing hormone –> TSH
Corticotropin releasing hormone –> ACTH
Prolactin inhibiting factor
- Actually is dopamine
- Released by the hypothalamus and causes a decrease in prolactin secretion
Hypothalamus and Posterior Pituitary
- PP does not receive tropic hormones through portal system
- Neurons in the hypothalamus send their axons down the pituitary stalk directly into PP which can then release oxytocin and ADH
OXytocin
Hormone that stimulates uterine contractions during labor as well as milk letdown during lactation
Also involved in bonding behavior
ADH
- Aka vasopressin increased reabsorption of water in the collecting ducts of the kidneys
- Secreted in response to increased plasma osmolarity or increased concentration of solutes within the blood
Prolactin
- Stimulates milk production in the mammary glands
- During pregnancy, estrogen and progesterone levels are high
- Release of dopamine decreases prolactin secretion
Milk Ejection
- Occurs when the newborn infant latches onto the breast
- Nipple stimulation causes activation of the hypothalamus resulting in two different reactions
- Oxytocin is released from the PP resulting in contraction of the smooth muscle of the breast and ejection of milk through the nipple
- Hypothalamus stops releasing dopamine onto the anterior pituitary allows prolactin release, causing production of milk and regulation of the milk supply
Endorphins
Decrease the perception of pain
Growth Hormone
- Promotes the growth of bone and muscle
- Energetically expensive and requires large quantities of glucose
- Prevnts glucose uptake in certain tissues (those that are not growing) and stimulates breakdown of fatty acids
- This increases the breakdown of glucose allowing muscle and bone to use it
ADH
Secreted in response to low blood volume or increased blood osmolarity
Action is at the level of the collecting duct where it increases the permeability of the duct to water
Net effect is a greater reabsorption of water from the filtrate in the nephron. This results in greater retention of water which results in increased blood volume and higher blood pressure
Triiodothyronine (T3) and Thyroxine (T4)
- Produced by the iodination of tyrosine in the follicular cells of the thyroid
- 3 and 4 refer to the number of iodine atoms attached to tyrosine
- Increased T3 and T4 will lead to increased cell respiration –> greater amount of protein and fatty acid turnover by speeding up synthesis and degradation of these compounds
Hypothyroidism
A deficiency of iodine or inflammation in the thyroid. Thyroid hormones are secreted in insufficient amounts of not at all
Condition characterized by lethargy, decreased body temperature, slowed respiratory, cold intolerance, weight gain
Hyperthyroidism
Excess of thyroid hormone. Heightened activity level, increaed body temperature, increased heart rate and weight loss
Calcitonin
- Produced by C-Cells from follicular cells
- Calcitonin acts to decrease plasma calcium levels by increasing calcium excretion from the kidneys, decreasing calcium absorption from the gut, and increasing storage of calcium in the bone
- High levels of calcium in the blood stimulate secretion of calcitonin from the C-cells
Parathyroid Glands
- Four small pea-sized structures that sit on the posterior surface of the thyroid
- Hormone produced: Parathyroid Hormone (PTH)
PTH
- Serves as an antagonistic hormone to calcitonin raising blood calcium levels
- Decreases excretion of calcium by the kidneys, increases absorption of calcium in gut by Vitamin D, and increases bone resorption freeing up calcium
- PTH is also subject to feedback inhibition
- As levels of plasma calcium rise, PTH secretion is decreased
- Affects phosphorus homeostasis by resorbing phosphate from bone and reducing reabsorption of phosphate in the kidney (promoting excretion in urine)
- Activates Vitamin D, which is required for the absorption of calcium and phosphate in the gut
Adrenal Glands
- Located on top of kidneys
- Each adrenal gland consists of cortex and a medulla
Adrenal Cortex
Secretes corticosteroids including: glucocorticoids, mineralocorticoids, cortical sex hormones
Glucocorticoids
- Steroid hormones that regulate glucose levels
- These hormones also affect protein metabolism
- Cortisol and Cortisone
- Released under control of adrenocorticotropic hormone
- CRF from hypothalamus promotes release of ACTH from ant pituitary which promotes release of glucocorticoids from adrenal cortex
Cortisol and Cortison
- raise blood glucose by increasing gluconeogenesis and decreasing protein synthesis
- Decrease inflammation and immunologic responses
- Cortisol known as stress hormone because it is released in times of stress which increases blood sugar and provides a ready source of fuel in case the body must react quickly to a dangerous stimuli
Mineralocorticoids
- Used in salt and water homeostasis
- Most profound effect on kidneys
- Ex: Aldosterone
Aldosterone
- Increases sodium reabsorption in the distal convoluted tubule and collecting duct of the nephron
- Water follows the sodium cations into the bloodstream increasing blood volume and pressure
- BP increases but plasma osmolarity unchanged
- Aldosterone also increases the reabsorption of potassium and hydrogen ions in same segments of nephron promoting their excretion in the urine
- Under control of renin-angiotensin-aldosterone system
Renin-angiotensin-aldosterone system
-Decreased BP causes the juxtaglomerular cells of the kidneys to secrete renin, which cleaves an inactive plasma protein, angiotensinogen, to its active form angiotensin 1. Angiotensin 1 is converted to angiotensin 2 by angiotensin-converting enzyme (ACE) in the lungs
Cortical sex hormones
- Adrenal glands also make cortical sex hormones (androgen and estrogens). Because males already secrete large quantities of androgens in the testes, adrenal testosterone plays a small role in male physiology
- Females are much more sensitive to disorders of cortical sex hormone production
- Certain enzyme deficiencies in the synthetic pathways of other adrenal cortex hormones result in excess androgen production in the adrenal cortex
Adrenal medulla
Responsible for production of sympathetic hormones epinephrine and norepinephrine.
Specialized nerve cells in the medulla are capable of secreting these compounds directly into the circulatory system
Epinephrine and Norepinephrine
Epinephrine can increase the breakdown of glycogen to glucose (glycogenolysis) in both liver and muscle as well as increase the basal metabolic rate
Both hormones will increase heart rate, dilate the bronchi, and alter blood flow to supply the systems that would be used in a sympathetic response..so vasodilation of blood vessels leading to the skeletal muscle, heart, lungs, and brain increasing bloodflow to these organs
Pancreas
- Exocrine and endocrine function
- Small groups of hormone producting cells are grouped into islets of Langerhans throughout the pancreas
- Islets contain alpha, beta, and delta cells
- Each cell type secretes a different hormone: alpha cells glucagon, beta insulin, and delta somatostatin
Glucagon
-Secreted during times of fasting
-When glucose levels run low the secretion of glucagon stimulates degradation of protein and fat, conversion of glycogen to glucose, and production of new glucose via gluconeogenesis
-Certain Gi hormone such as cholecystokinin and gastrin increase glucagon release from alpha cells
When glucose conc is high glucagon is inhibited
Insulin
- Antagonistic to glucagon and is secreted when glucose levels are high
- Insulin induces muscle and liver cells to take up glucose and store it as glycogen for later use
- Insulin also stimulates anabolic processes such as fat and protein synthesis
Hypoglycemia
-Caused by insulin with low blood glucose conc
Hyperglycemia
Underproduction or insensitivity to insulin (diabetes)
Excess Glucose and Kidneys
In kidneys excess glucose in the filtrate will overwhelm the nephron’s ability to reabsorb glucose resulting in its presence in the urine
Because it is an osmotically active particle and does not readily cross the cell membrane, the presence of glucose in the filtrate leads to excess excretion of water and an increase of the urine volume
Polyuria
Increased frequency of urination
Polydipsia
Increased thirst
Somatostatic
Inhibitor of both insulin and glucagon secretion. High blood glucose and amino acid concentrations stimulate its secretion. It is also produced by the hypothalamus where it functions to decrease growth hormone secretion in addition to its effects on insulin and glucagon
Pineal Gland
Locatd deep within brain and secretes hormone, melatonin. Blood levels of melatonin are at least partially responsible for sensation of sleepiness
Pineal gland receives projections directly from the retina but is not involved in vision
Erythropoietin
Stimulates bone marrow to increase production of erythrocytes (RBC’s) it is secreted in response to low oxygen levels in the blood
Produced by kidneys
Atrial Natriuretic Peptide (ANP)
- Released by heart to help regulate salt and water balance
- When cells in the atria are stretched from excess blood volume they release ANP
- ANP promotes excretion of sodium and increases urine volume
- This effect is antagonistic to aldosterone bc it lowers blood volume and pressure and has no effect on blood osmolarity
Thymosin
Released by thymus which is important for T cell development and differentiation
Thymus atrophies by adulthood and thymosin levels drop
Kinesin
Motor protein that is one of several different proteins that drive movement of vesicles and organelles along microtubules in axons. Drives anterograde movement from soma toward axon terminus
If a kinesin inhibitor is added to neurons in culture what is the likely result?
Atrophy of axons
If the potassium leak channels were blocked, wht would happen to the membrane potential?
The flow of potassium out of the cell makes the interior more negatively charged. Blocking the potassium leak channels would reduce the magnitude of the resting membrane potential making the interior less negative
What would happen to the membrane potential if sodium ions were allowed to flow down their concentration gradient?
Sodium ions would flow into the cell and reduce the potential across the plasma membrane, making the interior of the cell less negative and even relatively positive if enough ions flow into the cell
Repolarization
- Sodium channels close quickly and remain closed until resting membrane potential is reached
- Potassium channels open more slowly but stay open longer and even overshoot membrane potential by 20 mV . At this point they close. Potassium leak channels and the pump continue to work to bring membrane back to resting potential
Would an axon be able to conduct action potentials if its entire length were wrapped in myelin?
No, the action potential requires the movement of ions across the plasma membrane to create a wave of depolarization
How does myelin sheath speed the movement of action potentials?
By forcing the action potential to jump from node to node (saltatory conduction)
Equilibrium potential for Na
+50. If the interior of the cell is too positive, the positively charged ions repelled
Equilibrium potential for K
- Negative potential, -90
- If the interior of the cell is too negative, the positively charged ions cannot escape the attraction
If a neurotransmitter causes the entry of chloride into the postsynaptic cell, is the neurotransmitter excitatory or inhibitory?
Chloride ions are negatively charged so the entry of chloride ions into the cell will make the postsynaptic potential more negative so it is inhibitory
Signals can be sent in only one direction through synapses such as the neuromuscular junction. Which of the following best explains unidirectional signaling at synapses between neurons?
Signaling is unidirectional because only the presynaptic cell has vesicles of neurotransmitter that are released in response to action potentials and only the postsynaptic neuron has receptors that bind neurotransmitter to either depolarize or hyperpolarize the cell
Hydrophilic Hormones
Peptides and amino acid derivatives must bind to receptors on the cell surfae
Hydrophobic Hormones
Steroid hormones
Must bind to receptors in the cellular interior
Peptide Hormones
-Synthesized into the rough ER and modified in the Golgi. Stored in vesicles until needed when they are released by exocytosis. In bloodstream they dissolve in plasma since they are hydrophilic. Cannot cross biological membrane and must communicate with interior of target cell by second messenger cascade
Tropic hormones
hormones that control hormones
ACTH
adrenocorticohormone is secreted by the anterior pituitary and stimulates activity of the adrenal cortex which is responsible for secreting cortisol. ACTH is a tropic hormone because it does not directly affect physiological endpoints but merely regulates another regulator (cortisol). Cortisol regulates physiological endpoints including cell response to stress and glucose
Feedback regulation ACTH
The level of ACTH is influenced by level of cortisol. When cortisol is needed, ACTH is secreted and when cortisol increases sufficiently, ACTH secretion slows
CRH/CRF
Corticotropin releasing hormone causes increased secretion of ACTH. Just as ACTH secretion is regulated by feedback inhibition from cortisol, CRH secretion is inhibited by cortisol
Thyroid hormone
Produced from the amino acid tyrosine in the thyroid gland and comes in form of T3 and T4. The production of thyroid gland is increased by TSH from anterior pituitary which is regulated by hypothalamus and CNS. Tyrosine derived hormone but behaves like a steroid hormone; found within cells and not on surface
Aldosterone
Steroid hormone; It’s receptor would be found within target cells and not on their surface
Virus
- Infect all life forms on earth including plants, animals, protists, and bacteria
- Obligate intracellular parasite, so they are only able to reproduce within cells
- While within cells viruses have some of the attributes of living organisms such as the ability to reproduce but outside cells, viruses are without activity
- Unable to perform any of the chemical reactions characteristic of life
Viral structure
Possess a nucleic acid genome packaged in a protein shell. The exterior protein packaging helps to convey the genome from one cell to infect other cells. Once in a cell, the viral genome directs the production of new copies of the genome and of the protein packaging needed to produce more virus.
Viral genome
May consist of either DNA or RNA that is either single or double stranded and is either linear or circular. Viruses utilize ever conceivable form of nucleic acid as their genome. However, a given type of virus can have only one type of nucleic acid as its genome and a mature virus does not contain nucleic acid other than its genome
Adaptability of viruses
The exterior protein shell of a virus is typically a rigid structure of fixed size that cannot expand to accommodate a larger genome so the genome carries very few genes and relies on host-encoded proteins for transcription, translation, and replication
Capsid
Protein coat that surrounds the viral nucleic acid genome. Provides the external morphology that is used to classify viruses. It is made from a repeating pattern of only a few protein building blocks. Genome located within capsid head
Helical capsids
Rod shaped
Tail fibers of a virus
attach to the surface of the host cell as does the base plate
Sheath (virus)
Contracts using the energy of stored ATP, injecting the genome into the host
Viral infection
A virus binds to a specific receptor on the cell surface as the first step in infection. After binding, the virus will be internalized either by fusion with the plasma membrane or receptor mediated endocytosis. Only cells with receptors that match the virus will become infected explaining why only specific species or specific cell types are susceptible to infection
Bacteriophage Life Cycles
The first step in binding to the exterior of a bacterial cell in a process termed attachment. The next step is injection of the viral genome into the host cell in a process termed penetration or eclipse. Then the phage can follow the lytic cycle or the lysogenic cycle
Lytic Cycle of Phages
As soon as the phage genome has entered the host cell, host polymerases and/or ribosomes begin rapidly transcribing and translating it. One of the first viral gene products made: hydrolase a hydrolytic enzyme that degrades the entire host genome. Multiple copies of phage genome are produced as well as an abundance of capsid proteins. Then each capsid protein assembles itself around a new genome. Then lysozyme is produced which destroys the bacterial cell wall
Lysogenic cycle of phages
Problem with lytic cycle: all host cells are destroyed. Clever viruses enter the lysogenic cycle. Upon infection, the phage genome is incorporated into the bacterial genome and is now referred to as a prophage and the host is a lysogen. Prophage is silent and genes are not expressed and viral progeny not produced because transcription of phage genes is blocked by a phage-encoded repressor protein that binds to specific DNA elements in phage promoters (operators). Every time host cell reproduces itself, prophage is reproduced too. Eventually, prophages become activated. It now removes itself from host genome and enters lytic cycle
Consequence of lysogenic cycle
When the viral genome activates, excising itself from the host genome it may take part of the host genome along with it. When the virus replicates the small piece of host genome will be replicated and packaged with the viral genome
Transduction
If a virus integrates the stolen DNA from host genome with its own genome. It will code for a trait that the newly infected host did not previously possess such as the ability to metabolize glucose
RNA viruses (+)
- Must encode RNA-dependent RNA pol (and do not have to carry it)
- A (+) with a single stranded RNA genome is the simplest imaginable type of viral genome
- As soon as the (+) RNA genome is in the host cell, host ribosomes begin to translate it, creating viral proteins. The viral genome acts directly as mRNA (genome is infective) meaning injecting an isolated genome into the host cell will result in virus production. In order for the virus to replicate itself, one of the proteins it must encode must be an RNA-dependent RNA polymerase
JOB of RNA dependent RNA polymerase
to copy the RNA genome for viral replication; the host never makes RNA from RNA
(-) RNA Viruses
- Must carry RNA dependent RNA pol
- The genome of a - RNA virus is complementary to the piece of RNA that encodes viral proteins. The genome of a - RNA virus is the template for viral mRNA production. Must not only encode an RNA dependent RNA polymerase it must actually carry one with it in the capsid. When the virus enters the host cell, this enzyme will create a (+) strand from the (-) genome.
Retroviruses
- Must encode reverse transcriptase
- Ex: HIV undergoes lysogeny. They integrate into the host genome as proviruses.
What a viral genome does?
In order to integrate into our double stranded DNA genome, a viral genome must also be composed of double stranded DNA. Since these viral genomes enter the cell in an RNA for, they must undergo reverse transcription to make DNA from an RNA template. This is done by RNA-dependent DNA polymerase (reverse transcriptase) encoded by the viral genome
Three main retroviral genes
gag (codes for viral capsid proteins), pol (polymerase codes for reverse transcriptase), and env (codes for viral envelope proteins)
After integration of a retrovirus into the cellular genome, a reverse transcriptase inhibitor is added to the cell. Will the production of new viruses be blocked?
No reverse transcriptase is only required for one phase of the retrovirus life cycle: copying of RNA genome into DNA. so that it can integrate into host genome and be transcribed. Once the viral genome has integrated, transcription to prouduce viral mRNA and new viral RNA genome does not require reverse trascriptase. It can proceed with normal host cell enzymes
Double Stranded DNA Viruses
- Often encode enzymes required for dNTP synthesis and DNA replication
- Often have large genomes that include genes for enzymes involved in deoxyribonucleotide synthesis needed to make DNA
Prions
Do not follow Central Dogma (take translation and transcription out of equation) because they are self-replicating protein. The prion itself is a misfolded version of a protein that already exists.. When the normally folded protein comes into contact with the prion the prion acts as a template and normal protein is altered and become infectious
Transmissible spongiform encephalopathies
Prions responsible for this class of diseases. Causes degeneration in the nervous system especially the brain where characteristic holes develop and are always fatal. The misfolded proteins are found in the nervous tissues are very resistant to degradation by chemicals or heat making them hard to destroy
Fatal Familial Insomnia
An autosomal dominant condition inherited on chromosome 20. Prion diseases can be genetically linked through mutations in the gene that codes for the prion protein
Viroids
Consist of a short piece of circular, single stranded RNA (200-400 bases long) with extensive self-complementarity (it can base pair with itself to create some regions that are double stranded) Generally they do not code for proteins and they lack capsids. Some viroids are catalytic ribozymes while others when replicated produce siRNAs that can silence normal gene expression.
Replication of viroids
A viroid RNA dependent RNA polymerase synthesizes a (-) strand which is circularized by an RNA ligasederived from the host and then is used as the round rolling template to make more (+) copies that match the original viroid sequence. Viroids hijack the cell DNA dependent RNA polymerase and direct it to read RNA templates
Plasmid
Genetic element that can be found in prokaryotic cells. CIrcular piece of double stranded DNA which is much smaller than the genome. Plasmids are referred to as extrachromosomal genetic elements. They often encode gene products which may confer as advantage upon a bacterium carrying the plasmid (antibiotic resistance gene). Many capable of autonomous replication.
Bacterial Cell Membrane and the Cell Wall
Bacterial cytoplasm bounded by a lipid bilayer similar to human plasma membrane. Outside bilayer is a cell wall that provides support for the cell, preventing lysis due to osmotic pressure. Bacterial cell wall made of peptidoglycan, a complex polymer unique to prokaryotes containing cross linked chains made of surgars and amino acids.
Gram positive
Stain strongly to a dark purple color; have a thick peptidoglycan layer outside of the cell membrane and no other layer beyond this.
Gram negative
Stain weakly (a light pink color) have a thinner layer of peptidoglycan in the cell wall but have an additional outside layer containing lipopolysaccharide. Intermediate space bw cell membrane and outer layer is the periplasmic space where sometimes enzymes are found that degrade antibiotics
Endotoxins
Normal components of gram negative bacteria (outer membrane of it) that aren’t inherently poisonous. When many bacteria die and their disintegrated outer membranes are released into circulation cell sof immune system release so many chemicals that patient goes into septic shock causing blood to be released into tissue causing dip in blood pressure and other fatal problems. They have various chemical structures including: lipopolysaccharide, which contains sugars bound to lipids
Exotoxins
Are toxic secreted by gram negative and gram positive into surroudning medium. Exotoxins help the bacterium compete with other bacterial species such as normal inhabitants of the mammalian gut.
Capsule
Sticky layer of the polysaccharide goo surrounding the bacterial cell and often surrounding an entire colony of bacteria. It makes bacteria more difficult for immune system cells to eradicate and enables bacteria to adhere to smooth surfaces such as respiratory tract
Flagella
Long whip like filaments help bacterial motility. Can be monotrichous (flagellum located at one end), amphitrichous (flagellum located at both ends), or peritrichous (multiple flagella) Components of flagellum encoded by over 35 genes. Components = filament, hood, and basal structure. Basal structure contains a number of rings that anchor the flagellum to the inner and outer membrane for gram neg and serve to rotate the rod and the rest of the attached flagellum
Rotation of rod powered by
Diffusion of H+ down the proton gradient across the inner membrane by electron transport
Bacterial Motion
Can be directed toward attractants or away from toxins (chemotaxis). Connections between chemotaxis and flagellar propulsion is dependent upon chemoreceptors on the cell surface that bind attractants or repellants and transmit a signal that influences the direction of flagellar rotation. The response of flagellar rotation to chemical attractants is not dependent on an absolute concentration but to a change in the concentration over time. As bacterium moves through solution it is able to detect whether it is moving toward or away from the highest concentration and respond accordingly
Pili
Long projections on the bacterial surface involved in attaching to different surfaces.
Sex pilus
Special pilus attaching F+ Male and F- female bacteria which facilitates the formation of conjugation bridges
Fimbriae
Smaller structures that are not involved in locomotion or conjugation but are involved in adhering to surfaces
Bacteria and temperature
Bacteria have ability to tolerate environmental variables. Each bacteria has an optimal growth temperature. Most bacteria favor mild temperatures similar to the ones that humans and other organisms favor (30 degrees) they are called mesophiles.
Thermophiles
Can survive temperatures up to 100 degrees in boiling hot springs or near geothermal vents in the ocean floor.
Psychrophiles
Thrive at very low temperatures near 0 degrees
Autotrophs
utilize carbon dioxide as their carbon source
Heterotrophs
rely on organic nutrients created by other organisms
Chemotrophs
Get their energy from chemicals
phototrophs
get their energy from light
Chemoautotrophs
Build organic macromolecules from carbon dioxide using the energy of chemicals. They obtain energy by oxidizing inorganic molecules like H2S
Chemoheterotrophs
Require organic molecules such as glucose made by other organisms as their carbon source and for energy
Photoautotrophs
Use only carbon dioxide as a carbon source and obtain their energy from the sun
Photoheterotrophs
Odd in that they get their energy from the Sun like plants but require an organic molecule made by another organism as their carbon source
Minimal medium
contains nothing but glucose in addition to the agar
Lawn
Dense growth of bacteria seen in Petri dishes
Plague
Clear in the lawn
Auxotroph
Bacterium which cannot survive on minimal medium because it can’t synthesize a molecule it needs to live. It requires an auxiliary trophic substance to live. It requires an auxiliary trophic substance to live.
Facultative anaerobes
Will use oxygen when its around but they don’t need it
Tolerant anaerobes
Can grow in the presence or absence of oxygen but do not use it in their metabolism
Obligate anaerobes
Poisoned by oxygen. This is because they lack certain enzymes necessary for the detoxification of free radicals which form spontaneously when oxygen is around
Respiration vs Fermentation
Respiration is glucose catabolism with use of an inorganic electron acceptor such as oxygen. Fermentation is glucose catabolism which does not use an electron acceptor such as oxygen; instead a reduced by-product of glucose catabolism such as lactate or ethanol is given off as waste
Anaerobic respiration
Refers to glucose metabolism with electron transport and oxidative phosphorylation relying on an external acceptor other than O2
Binary fission
Each bacteria grows in size until it has synthesized enough cellular components for two cells rather than one replicated its genome and then divides in two
Bacterial Life Cycle
Growth is exponential (log phase)
- Prior to achieving exponential growth, bacteria that were not previously growing undergo a lag phase, during which cell division does not occur even if the growth conditions are ideal. Cells that are not actively producing components that are needed for cell division such as dNTPs. The lag period is a time when biosynthetic pathways are very strictly producing new cellular components so that cells can then begin to divide
- As metabolites in the growth medium are depleted and metabolic waste products accumulate, the bacterial population passes from log phase to stationary phase in which cells cease to divide for lack of nutrients. IN the last stages of the stationary phase, cell death may occur as a result of the medium’s inability to support growth
Endospore Formation
Some types of gram positive bacteria form endospores under unfavorable growth conditions. They have tough, thick external shells comprised of peptidoglycan. Within endospore are found the genome, ribosomes, and RNA which are required for the spore to become metabolically active when conditions become favorable. They are able to survive temperatures above 100 degrees. Metabolic reactivation is termed germination. A single bacterium is able to form only one sperm per cell
Transduction
Transfer of genomic DNA from one bacterium to another by a lysogenic phage
Transformation
If pure DNA is added to a bacterial culture, the bacteria internalize the DNA in certain conditions and gain any genetic information in the DNA
Conjugation
Bacteria make physical contact and form a bridge between the cells. Once cell copies DNA and this copy is transferred through the bridge to the other cell. Bacteria that have the F factor are male of F+ and will transfer the F factor female cells. Bacteria that do not contain the F factor are female F- and will receive the F factor from males cells to become male.
F factor
A single circular DNA molecule. Although much smaller than the bacterial chromosome, it contains several genes many of which are involved in conjugation itself. After the male cell produces sex pili and the pili contact a female cell, a conjugation bridge forms. The F factor is replicated and transferred from the F+ to the F- cell. DNA transfer between F+ and F- cells is unidirectional. Although it is extrachromosomal it does sometime become integrated into the bacterial chromosomes through recombination.
Archaea
Organisms that live in the world’s most extreme environments they differ from other bacteria because their cell wall lacks peptidoglycan. Genetically, they share traits with eukaryotes including the presence of introns and the use of many similar mRNA sequences. They are single celled so they reproduce via fission or budding
Parasitic Bacteria
Can be either obligate (must be inside a host cell to replicate) or facultative (that they can live and replicate inside or outside of a host cell). Damage is being done to the host cell. However to ensure a continued supply of energy and cellular materials needed to survive and reproduce parasitic bacteria need to modulate the course of that damage
Mycobacteria
The genus of bacteria which encompasses the cause of tuberculosis as well as other diseases has members which are obligate and others which are facultative
Symbiotic bacteria
Coexist with a host where both the bacterial cell and the host cell derive a benefit. Ex: Rhizobia genus which is responsible for the fixing of nitrogen in the nodules that exist in the roots of legumes.
Cyanobacteria
Responsible for nitrogen fixing in marine environments
Tendons
Strong connective tissue formed primarily of collagen; attaches muscle to bone
Antagonistic vs Synergistic
Muscles that are responsible for movement in opposite directions are antagonistic and muscles that move a joint in the same direction are synergistic
Sarcolemma
Cell membrane of the myofiber that is made of the plasma membrane and an additional layer of polysaccharide and collagen. This additional layer helps the cell to fuse with tendon fibers. Each myofiber has myofibrils which are like specialized organelles responsible for the striated appearance of skeletal muscle and generates the contractile force of skeletal muscle
Sliding Filament Cycle
- Binding of the myosin head to a myosin binding site on actin also known as cross bridge formation. At this stage, myosin has ADP and Pi bound
- The power stroke, in which the myosin head moves to a low energy conformation, and pulls the actin chain toward the center of the sarcomere. ADP is released
- Binding of a new ATP molecule is necessary for release of actin by the myosin head
- ATP hydrolysis occurs immediately and the myosin head is cocked (set in a high energy conformation). Another cycle begins when the myosin head binds to a new binding site on the thin filament
These steps occur spontaneously
When does contraction occur in the myofiber
Only when the cytoplasmic Calcium increases. This is because in addition to polymerized actin, the thin filament contains the troponin-tropomyosin complex that prevents contraction when the Calcium is not present
Tropomyosin
Long fibrous protein that winds around the actin polymer blocking all the myosin binding sites
Troponin
Globular protein bound to the tropomyosin that can bind Calcium. When troponin binds Calcium troponin undergoes a conformational change that moves tropomyosin out of the way so that myosin heads can attach to actin and filament sliding can occur
Neuromuscular junction
The synapse between an axon terminus (synaptic knob) and a myofiber. Not a single point but rather a long trough or invagination of the cell membrane. Elongated to fill the long synaptic cleft. Purpose is to allow the neuron to depolarize a large region of the postsynaptic membrane at once
Impulse Transmission at the NMJ
Typical of chemical synaptic transmission; action potential arrives at axon terminus triggering opening of calcium channels resulting in increase in intracellular ca triggers the release of vesicles of acetylcholine which must diffuse across synaptic cleft and bind to ACh receptor resulting in postsynaptic sodium influx which depolarizes postsynaptic membrane Depolarization = end plate potential. ACh will continue to stimulate postsynaptic receptors until it is destroyed by acetylcholinesterase. Summation is required to initiate an AP in the postsynaptic cell. Single MEPP is insufficient to cause myofiber to contract. When a sufficient EPP occurs, threshold is reached and sodium channels open . This initiates a AP in the myofiber propagated by neurons. The AP must depolarize the entire myofiber if contraction is to occur but APs only occur at the cell surface because they are by nature a depolarization of the cell membrane and the myofiber is so thick that an AP on its surface will not depolarize its interior. the T tubules are the solution
T Tubules
Deep invaginations of the cell membrane which allow the AP to travel thick into the thick cell
Sarcoplasmic reticulum
Huge, specialized smooth ER which enfolds each myofibril in the cell. SR is specialized to sequester and release Calcium.
Twitch
Smallest measurable muscle contraction
How does the nervous system increase the force of contraction?
- Motor Unit Recruitment: Motor unit is a group of myofibers innervated by the branches of a single motor neuron’s axon. Results from the activation of one motor neuron and a larger twitch can be obtained by activating more motor neurons..
- Frequency Summation: Each contraction ends when the SR returns the Calcium to low resting levels. If a second contraction occurs rapidly, there is insufficient time for the Ca to be sequestered by the SR and the second contraction builds on the first. Force of contraction increases. Rapidly repeating series of stimulations results in the strongest possible contraction (tetanus)
Energy Storage in the myofiber
Glycolysis and the TCA cycle are not fast enough to keep pace with the rapid ATP utilization during extended contraction. Creatine phosphate fulfills need for an intermediate term energy storage molecule
Type 1 Slow Twitch Fibers
Fibers also known as red slow twitch or red oxidative fibers because of their high myoglobin content. They have a much better blood supply than fast twitch fibers due to an extensive capillary network. Combination of good oxygen delivery from blood stream and ability to store oxygen on their myoglobin allows these fibers to maintain contraction for extended periods of time without fatigue (marathon runners)
Type 2A Fast Twitch
Fast twitch oxidative fibers somewhat resistant to fatigue. They cannot maintain activity for as long as slow twitch fibers (around 30 minutes) but far exceed the duration of use by Type2Bfibers
Type 2B Fibers
Known as white fast twitch fibers due to their lack of mitochondria; these fibers contract with great force. they fatigue just as quickly maxing out around one minute of use. Provide the explosive force needed for jump shots and pole vaults
Cardiac muscle and skeletal muscle similarities
- Thick and thin filaments striations
- T tubules
- Troponin-tropomyosin regulates contraction
- Length tension relationship affects cardiac more: Increasing the amount of blood that returns to the heart can stretch cardiac muscle to optimize the length tension relationship and maximize cardiac output
Cardiac muscle and skeletal muscle differences
- Cardiac muscle cells are not structurally (but yes functionally) syncytial (they each have one nucleus) while skeletal muscle cells are syncytial.
- Cardiac muscle cells connected to neighbors by intercalated disks which allow action potentials to propogate throughout the entire nuclei
3 Some of the Calcium required for cardiac muscle cell contration comes from the extracellular environment through the voltage gated Calcium channels. Skeletal muscles all the Calcium for contraction comes from the sarcoplasmic reticulum - Does not depend on stimulation by motor neurons (cardiac muscle). Most important nerve releasing ACh at synapses with the heart in inhibitory (vagus nerve) Synapses with the sinoatrial node where it releases ACh to inhibit spontaneous depolarization with the result being a slower heart rate. In skeletal neurons release ACh to stimulate contraction
- The AP in cardiac muscle depends not only on the sodium channels as in skeletal muscle) but also on voltage gated calcium channels (slow channels) becaue they respond more slowly to threshold depolarization opening later than the fast channels and talking longer to close
Plateau phase of cardiac muscle cell action potential
- Longer duration of concentration facilitates ventricular emptying (better ejection fraction) and 2. longer refractory period helps prevent disorganized transmission of impulses throughout the heart and makes summation and tetanus impossible.. Advantageous because the heart must relax each after contraction. Skeletal have steeply spiking AP while cardiac muscle cells have a spike and a plateau
Smooth muscle and skeletal muscle
Actin and myosin; triggered by increase in cytoplasmic Ca, do not branch
Differences smooth muscle and skeletal muscle
- Much narrower and shorter than skeletal muscle cells
- T tubules not present
- Each smooth muscle has only one nucleus and is connected to neighbors by gap junctions which allow impulses to spread from cell to cell
- Thick and thin filaments not organized in sarcomeres in smooth muscle. Instead they are dispersed in the cytoplasm
- troponin-tropomyosin complex not present. Contraction is regulated by calmodulin and myosin light chain kinase. Calmodulin binds Ca and then activates MLCK. MLCK phosphorylates a portion of myosin molecule thus activating its activity
- Smooth muscle cells have almost no sodium fast channels it takes ten to twenty times as long as a skeletal muscle action potential
- Some smooth muscle that must sustain prolonged contractions has action potentials similar to those of cardiac
- Smooth muscles have a constantly fluctuating resting potential. Ions pass through gap junctions between neighboring cells causing the changes in resting potential to propagate like waves through the connected smooth muscle cells. These fluctuations in resting potential are called slow waves are not spike potentials and do not elicit muscle contractions but they are necessary to help coordinate the action potentials
- Smooth muscles are innervated by motor neurons (like skeletal muscle) but for smooth they are autonomic motor neurons not somatic.
Connective tissue
Derived from a single pregenitor, the fibroblast. This name derives from ability to secrete fibrous material such as collagen, a strong fibrous protein. It is primarily extracellular material with a few cells scattered in it. Consists of ground substance (thick viscous material) and matrix (with fibers)
Fibroblast derived cells
Adipocytes, chondrocytes, osteocytes
Ingredient of ground substance
proteoglycans; large macropolymers consisting of protein core with many attached carbohydrate chains. The carbohydrate chains are called glycosaminoglycans and like all carbohydrates, they are very hydrophilic. Surrounded by large body of water which gives them their characteristic thickeness and firmness
Loose connective tissue
basically packing tissue and include areolar tissue (soft material located between most cells throughout the body) and adipose tissue
Dense connective tissue
Tissues that contain large amounts of fibers (esp collagen) such as tendonds, ligaments, cartilage, bone
Flat bones
Ex: scapula, ribs, and the bones of the skull
Important for protection of organs
Ingredients of bone
Hydroxyapatite and collagen; hydroxyapatite is a solid material consisting of calcium phosphate crystals. During bone synthesis, collagen is laid down in a highly ordered structure Then crystals form around the collagen framework giving bone its characteristic strength and inflexibility
Compact Bone Organization
unit of compact bone structure is the osteon. In the center is a hole called the central canal which contains blood, lymph, and nerves. Surrounding the canal are concentric ring of bone termed lamellae. Tiny channels or canaliculi branch out from the central canal to spaces called lacunae. In each lacuna is an osteocyte or mature bone cell. Osteocytes have long processes which extend down the canaliculi to contact other osteocytes (exchanging nutrients and wastes)
Cartilage
Strong but very flexible extracellular tissue secreted by cells called chondrocytes. Three types of cartilage (hyaline, elastic, fibrous).
Hyaline
Strong and somewhat flexible. Larynx and trachea are reinforced by hyaline cartilage and joints are lined by hyaline cartilage known as auricular cartilage
Elastic cartilage
found in structures that require support and more flexibility than hyaline cartilage can provide; it contains elastin
Fibrous cartilage
Very rigid and is found in places where very strong support is needed such as the pubic symphysis and the invertebral disks of the spinal column
Ligaments
connect bones to other bones
tendons
connect bones to muscles
Joint
point where one bone meets another
Immovable joints
Synarthroses
Basically points where two bones are fused together
Amphiarthorses
Slightly movable joints
Provide both movability and a great deal of support
Diarthroses
Freely movable joints
Synovial fluid
Lubricating movable joints kept within the joint by the synovial capsule
Articular cartilage
The surfaces of the two bones that contact each other are perfectly smooth because they are lined by this cartilage. Easily damaged b overuse or infection
Endochondral ossification
Hyaline cartilage is produced and then replaced by bone
Intramembrous ossification
synthesis of bone from an embryonic tissue called mesenchyme
Growth of long bones
Structure called epiphyseal plate is seen between diaphysis and epiphysis, As chondrocytes divide, this epiphsis and diaphysis are forced apart. Then the cartilage is replaced by bone
Goals of circulatory system
- Distribute nutrients from digestive tract, liver, and fat tissue
- Transport oxygen from lungs to entire body and CO2 from the tissues to the lungs
- Transport metabolic wastes from tissues to excretory system
- Transport hormones from endocrine glands to targets and provide feedback
- Maintain homeostasis of body temperature
- Hemostasis (blood clotting)
Perfusion
flow of blood through a tissue
Ischemia
Inadequate blood flow results in tissue damage due to shortages of O2, nutrients, and buildup of metabolic wastes
Hypoxia
When adequate circulation is present but the supply of oxygen is reduced
Arteries
Vessels that carry away blood from the heart at high pressure
Veins
Vessels that carry blood back toward the heart. Except for the largest vessels near the heart, veins lack a muscular wall
Arterioles
As arteries pass further from the heart, they pressure of blood decreases and they branch into increasingly smaller arteries. Have smooth muscle in their walls that can act as a control valve to restrict or increase the flow of blood into the capillaries of tissues
Capillaries
What arterioles pass into; very small vessels often just wide enough for a single blood cell to pass. Have thin walls made of a single layer of cells and are designed to allow the exchange of material between the blood and the tissues.
Venules
After passing through capillaries blood collects in these small veins and then into the veins leading back to the heart
If the arterioles constrict in a tissue, will material diffuse through the wall of the arterioles into the tissue?
No, all exchange of material between the blood and tissues must occur in capillaries. The walls of arterioles are too thick and muscular for exchange to occur
Endothelial Cells in Blood Vessels
- Vasodilation and vascoconstriction: secretion of substances like nitric oxide and endothelin can regulate vessel diameter
- Inflammation: release of inflammatory chemicals stimulates endothelial cells to increase expression of adhesion molecules which allow white blood cells to adhere to endothelial cells and enter injured tissue
- Angiogenesis: growth factors stimulate endothelial cells to break free from existing vessel and proliferate in surrounding tissue forming new vessels together
- Thrombosis: Undamaged endothelial cells secrete substances that inhibit coagulation cascade preventing formation of clots inside unbroken vessels
Endothelial Cell Dysfunction
Leads to pathogenic conditions including: hypercholesterolemia, hypertension, clot formation, coronary artery disease, atherosclerosis
Hepatic Portal System
Blood passes through capillaries in the intestine then collects in veins to travel to liver where the vessels branch and the blood passes through capillaries
Portal System Benefit
Evolved as direct transport systems, to transport nutrients directly from the intestine to the liver or hormones from the hypothalamus to the pituitary without passing through the whole body
Coronary arteries
Very first branches from the aorta which branch to supply blood to the wall of the heart. they encircle the heart forming a crown shape
Coronary Veins
Deoxygenated blood from hear collects here and merges to form coronary sinus located beneath a layer of fat on the outer wall of the heart
Coronary sinus
Blood here is the only oxygenated blood that does not end up in the inferior vena cava or superior vena cava. Instead coronary sinus drains into right atrium
Valves
Necessary to ensure one way flow through the circulatory system. Valves in heart are important since the pressure differentials are so extreme. Ventricular pressure is higher than atrial pressure
Bicuspid Valve
Must withstand enormous pressures
Venous Valves
In passing through capillaries, blood loses its pressure. Thus, there is not much of a driving force pushing it toward the heart. Contraction of skeletal muscle becomes important because normal body movements push and squeeze the veins pressurizing venous blood and pushing it along. Venous valves prevent backflow as long as the valves hold up blood moved toward the heart. When the valves fail, varicose veins result
Diastole
Ventricles are relaxed and blood is able to flow into them from the atria. Atria contract during diastole to propel blood into the ventricles more rapidly. At the end of diastole, ventricles contract initiating systole
Systole
Pressure in the ventricles increase rapidly until the semilunar valves fly open and blood rushes into the aorta and pulmonary artery. Ventricles are contracting beginning at the lub sound and ending at the dup. At the end of systole, ventricles are empty and stop contracting. Pressure inside falls rapidly and blood begins to flow backward from the pulmonary artery into the right ventricle and from the aorta into the left ventricle. But very little backflow occurs because th semilunar valves shut when pressure in ventricles becomes lower than pressure in the great arteries. Full cardiac cycle done and is back in diastole
lub
Results from the closure of the AV valves at the beginning of systole
Dup
Sound of semilunar valves closing at the end of systole
Heart rate
Is the number of times the lub-dup cardiac cycle is repeated per minute. The normal pulse is about one beat per second. A stronger heart pumps more blood each time it contracts and thus may beat fewer times per minute and still provide adequate circulation
Stroke Volume
Amount of blood pumped with each systole
Cardiac Output
Total amount of blood pumped per minute defined by the equation: cardiac output (L/min) = stroke volume (L/beat) x heart rate (beats/min) CO = SV x HR
Frank Starling mechanism
If the heart muscle is stretched, it will contract more forcefully. It will be more stretched by filling it with more blood. If venous return is increased the heart fills more and muscle fibers are stretched and they respond by contracting more forcefully. The more blood the heart receives from the tissues, the more it pumps out to the tissues
Two principal ways to increase venous return
- Increasing the total volume of blood in the circulatory system (retaining water)
- Contraction of large veins can propel blood toward the heart
Functional syncytium
- Cardiac Muscle is one
- A syncytium is a tisssue in which the cytoplasm of different cells can communicate via gap junctions.
- Gap junctions found in intercalated disks, the connections between cardiac muscle cells
- Depolarization can be communicated directly through the cytoplasm to neighboring cardiac muscle cells through these gap junction
Slow calcium channel
These channels open in response to a change in membrane potential to a specific voltage (threshold voltage) and when open allow the passage of calcium down its gradient. These channels also stay open longer than the fast sodium channels do, causing the membrane depolarization to last longer in cardiac muscle than in neurons producing a plateau phase
T Tubules
To maximize the entry of calcium in the cell, cardiac muscle has involutions of the membrane. Action potential travels down these involutions (t-tubules) allowing the entry of calcium from the extracellular environment and also induce the sarcoplasmic reticulum to release calcium. Calcium causes the contraction actin myosin fibers
Sinoatrial node
- Initiates each action potential that starts each cardiac cycle. Divided into three phases: Phase 0, Phase 3, and Phase 4
- Unstable resting potential. Phase 4 (automatic slow depolarization) and is caused by special sodium leak channels that are responsible for its rhythmic automatic excitation. This inward sodium leak brings the cell potential to the threshold for voltage gated calcium when they open they cause Phase 0
- Phase 0: upstroke of the pacepaker potential. Caused by inward flow of Calcium
- Phase 3: repolarization. Caused by closure of the Ca channels and opening of the K channels leading to an outward flow of K from the cell
Phases of action potential in cardiac muscle cells
-Phase 0: Fast Na channels open
na influx
-Phase 1: Na channels inactivate; k channels open; k efflux
-Phase 2: Ca channels open; ca influx; k channels still open; k efflux
-Phase 3: Ca channels close; K channels still open; K efflux
-Phase 4: K channels close
Regulation of heart rate by autonomic nervous system
- Does not initiate the action potentials in the heart but does regulate the rate of contraction
- Reason the normal heart rate is 60-80 bpm is that the parasympathetic nervous system continually inhibits depolarization of the SA node
- Postganglionic neurons innervate the SA node releasing acetylcholine which inhibits depolarization by binding to receptors on the cells of the SA node
- Sympathetic system kicks in when increased cardiac output is needed during a fight or flight response. Sympathetic postganglionic neurons directly innervate the heart releasing norepinephrine and epinephrine binds to receptors on cardiac muscle cells
Vagal tone
Constant level of inhibition provided by the vagus nerve
Baroreceptors
In the aortic arch and in the carotid arteries that monitor pressure. When they notify the CNS that the pressure is too high, the CNS sends out information to correct the problems; increased vagal tone and decreased sympathetic input. When the pressure is too low, opposite happens
Hemodynamics
Study of blood flow
Ohm’s Law
Delta P = Q x R
Delta P is the pressure gradient
Q stands for blood flow or cardiac output
R denotes resistance
How can we change blood flow?
We can only change it by changing either the pressure (varied by increasing the force) or the resistance which is controlled by precapillary sphincters.
Peripheral resistance
Controlled by sympathetic nervous system Basal level of pressure is provided b constant level of norepinephrine released by sympathetic postganglionic axons innervating precapillary sphincters (input is known as adrenergic tone).
Sympathetic system can increase overall peripheral resistance thus increasing BP. It can also divert blood away from one tissue so that another is preferentially perfused. Activation causes sphincters in the gut to contract while arterioles supplying skeletal muscle are allowed to relax so that blood is diverted from the gut to skeletal muscle helping fight or flight
Systemic arterial pressure
Force per unit exerted by blood on the walls of arteries
120/80
120- systolic pressure. Very loud the sound comes from blood slamming into arteries (which are constricted by the cuff) each time the heart beats
80- diastolic pressure: lowest arterial pressure occurring at any time during the cardiac cycle
120 is the highest pressure that occurs in the circulatory system of the patient during the time the BP is taken. This level is attained as the ventricles contract (during systole).
80 mm Hg is as low as the pressure gets between heartbeats (during diastole)
Local autoregulation
Tissues in need of extra blood flow are able to requisition it themselves. Certain metabolic wastes have a direct effect on arteriolar smooth muscle causing it to relax. When a tissue is underperfused, wastes build up, and vasodilation occurs automatically. Principal determinant of coronary blood flow
Plasma
55 percent of blood volume and consists of electrolytes, buffers, sugars, blood proteins, lipoproteins, CO2, O2, metabolic wastes
Blood proteins
Most of which are made by the liver, include albumin, immunoglobins, fibrinogen, and lipoproteins
Albumin
Essential for maintenance of oncotic pressure (osmotic pressure in the capillaries due only to plasma proteins)
Immunoglobins
Key part of the immune system
Fibrinogen
Essential for blood clotting
Lipoproteins
Large particles consisting of fats, cholesterol, and carrier proteins. Their role is to transport lipids in the bloodstream
Ure
Principal metabolic waste product a breakdown product of amino acids. Basically a carrier of excess nitrogen
Bilirubin
Breakdown product of heme
Bone marrow stem cells
All the formed elements of the blood develop here from these in the bone marrow
Erythropoeitin
Hormone that is made in the kidney that stimulates RBC production in the bone marrow
Erythrocyte
Cell but has no nucleus or other organelles. Does require the energy of ATP for processes such as ion pumping and basic maintenance of cell structure during 120 day lifetime
- Lacking mitochondria, it relies on glycolysis for ATP synthesis
- Purpose of RBC is to transport oxygen to the tissues from the lungs and CO2 from the tissues to the lungs
Hemolytic disease of the newborn
Dangerous in the case of an RH- mother carrying a Rh+ baby. If it is the first baby there are no complications unless the mother had been previously sensitized. ON delivery some Rh+ from the child can mix with the mothers Rh- blood and lead to her sensitization. Future Rh+ babies are then at risk, since the anti-Rh antibodies can cross the placental barrier to clump and/or destroy the Rh+ baby’s red blood cells
Role of WBC’s
fight infection and dispose of debris
White Blood Cells
-Large complex cells with all the normal eukaryotic cell structures (nucleus, mitochondria)
Macrophages and Neutrophils
Move by amoebic motility (crawling) so they are able to squeeze out of capillar intercellular junctions and can roam free in the tissues hunting for foreign particles and pathogens
Chemotaxis
Movement directed by chemical stimulus
B cell
Mature into plasma cell and produce antibodies
T cell
Kill virus infected cells, tumor cells, and reject tissue grafts, also control immune response
Eosinophil
Destroy parasites; allergic reactions
Basophil
Store and release histamine; allergic reactions
Platelets
-Have no nuclei and a limited lifespan
-Derived from fragmentation of megakaryocytes (large bone marrow cells)
-Function is to aggregate at the site of damage to a blood vessel wall forming a platelet plug
Helps to stop bleeding
Fibrin
Threadlike protein which forms a mesh that holds the platelet plug together. When the fibrin mesh dries, it becomes a scab which seals and protects the wound. Plasma protein fibrinogen is converted into fibrin by protein thrombin when bleeding occurs
Thrombus
Blood clot, is a scab circulating in bloodstream. Calcium as well as many accessory proteins are necessary for the activation of thrombin and fibrinogen
Heme
Large multi ring structure that has a single iron atom bound at its center. The role of heme with its iron atom is to bind oxygen.
Hemoglobin Binding Cooperative
When none of the subunits have oxygen bound, all four subunits assume a tense conformation that has a relatively low affinity for oxygen. When one of the subunits binds to oxygen, its conformation changes from a tense to a relaxed state that has a higher affinity for oxygen. The change in the 3-D structure of the subunit with oxygen bound is then communicated to the other subunits through contacts between the polypeptides to alter their conformation and increase their conformation as well. Hemoglobin binds cooperatively
Hemoglobin _affinities
Level of O2 in active tissues is very low because they use it in oxidative phosphorylation. Thus in the tissues, hemoglobin has low affinity for oxygen and tends to release any oxygen it carries. When a RBC is passing through capillary in the lungs the hemoglobin it contains will have higher affinity due to cooperative binding and will tend to bind oxygen very strongly. Result is that a lot of oxygen picked up by RBC in the lungs and most of it is released as they pass through active tissues that need oxygen
Certain factors stabilize the tense configuration of hemoglobin
decreased pH, increased level of carbon dioxide in the blood, increased temperature
(bohr effect)
Percent saturation
= (# of O2 molecules bound) / (# of O2 binding sites) x 100%
Can quantify affinity of hemoglobin for oxygen. If hemoglobin is in the relaxed configuration then as more oxygen becomes available much more of it will be bound up. But if it is in the tense configuration, the tendency to bind oxygen is reduced and less will be bound
How is Carbon dioxide transported in the blood
- Conversion of Carbon dioxide to carbonic acid which can dissociate into bicarbonate and a proton which are really water soluble and are easily carried in the blood. Conversion catalyzed by carbonic anhydrase
- Transported by being stuck onto hemoglobin. It does not bind to oxygen binding sites but onto other sites on the protein. It stabilizes tense Hb
- More water soluble than oxygen so a lot is dissolved in the blood and carried from tissues into the lungs
Chylomicron
Type of lipoprotein that fats are absorbed from the intestine and packaged as
They enter tiny lymphatic vessels in the intestinal wall called lacteals which empty into larger lymphatics which eventually drain into a large vein near the neck
Why does water have a great tendency to flow out of capillaries through the clefts?
- Hydrostatic pressure created by the heart tends to squeeze water out of the capillaries
- High osmolarity of the tissues tends to draw water out of the bloodstream
Osmolarity of plasma
Plasma has a high osmolarity. Provided by high concentrations of large plasma proteins, mainly albumin. Albumin is too large and rigid to pass through the clefts so it remains in the capillaries and keeps water there too. Osmotic pressure provided by plasma proteins is called oncotic pressure
Capillary and Pressure
- At beginning of capillary, hydrostatic pressure is high. Results it that water squeezes out into the tissues
- As water continues to leave the capillary, the relative concentration of plasma proteins increases
- At the end of the capillary, the hydrostatic pressure is quite low but since blood is now concentrated the oncotic pressure is high. As a result water flows back into the capillary from the tissues
Capillaries during inflammation
Capillaries dilate increasing the size of the intercellular clefts. This allows more space for WBC to migrate into the tissues. Unfortunates side effect is that plasma proteins and a lot of water are lost into tissues (edema)
Lymphatic system
Lymphatic capillaries -> lymphatic vessels -> Lymphatic ducts -> Thoracic duct in chest -> Empties into large vein in neck
Lymphatic vessels
Have valves; fluid is called lymph and is filtered by lymph nodes that contain WBC’s that can initiate an immune response against anything foreign that may have been picked up in the lymph
Innate Immunity
Refers to general nonspecific protection the body provides against various invader.
Ex’s:
1. Skin
2. Tears, saliva, and blood contain lysozyme an enzyme that kills some bacteria by destroying their cell walls
3. Acidity of the stomach
4. Macrophages and neutrophils
5. Complement system is a group of about 20 blood proteins that can bind to surface of foreign cells leading to their destruction
Humoral immunity
Refers to specific protection b proteins in the plasma called antibodies or immunoglobulins. Antibodies recognize and bind to microorganisms leading to destruction and removal from body. Each antibody molecules has light chain and heavy chains joined by disulfide bonds. Each antibody has two regions, the constant region and the variable (antigen binding) region
Variable regions
Responsible for specificity of antibodies in recognizing foreign particles
IgM
Located in blood and B cell surface. Function is involved in initial immune response; pentameric structure in blood and monomeric structure on B cell as antigen receptor
IgG
found in blood and functions as involved in ongoing immune response; represents majority of antibody; can also cross placental barrier
IgD
Found in B cell surface; Serves with IgM as antigen receptor on B cell
IgA
Found in secretions helps protect newborns
IgE
found in blood and is involved in allergic reactions
Epitope
Small site that an antibody recognizes within a larger molecule
Carrier
Very small molecules do not start production of antibodies on their own but will when bound to an antigenic large molecule like a protein which is a carrier and the small molecule that became antigenic is a hapten
How do B cells produce a broad array of antibodies?
Immature B cells are derived from precursor stem cells in the bone marrow. The genes that encode antibody proteins are assembled by recombination from many small segments during B cell development. Many different B cell clones with variable region. Immature B cells express antibody molecules on their surface. When antigen binds to antibody on the surface of a specific immature B cell, that cell is stimulated to proliferate into one of two cells: plasma and memory cells
Plasma Cells
Actively produce and secrete antibody protein into the plasma.
Memory Cells
Produced from the same clone and have the same variable regions but do not secrete antibody; they are like preactivated dormant B cells. Waiting for antigen to reappear. It it does, then memory cells become activated and begin producing antibody quickly so that no symptoms of illness appear.
two types of T cells
T helpers (CD4) and T killers (cytotoxic T cells CD8)
Role of T helper
Activate B cells, T killer cells, and other cells of the immune system. T-helper is the central controller of the whole immune response. It communicates with other cells by releasing special hormones called lymphokines and interleukins
Host of HIV
Kills: Virus infected hot cells, Cancer cells, and foreign cells such as cells of a skin graft given by incompatible donor
T cells
Stands for thymus because this is where they develop during childhood. Trillions of different T cells produced in bone marrow. Each of these is specific for an antigen just as with B cells. Does not release antibodies. Protein on the T cell surface that can bind antigen is T cell receptor
MHC1 proteins
Found on surface of ever nucleated cell in the body and role is to randomly pick up peptides from the inside of the cell and display them on the cell surface. This allows T cells to monitor cellular contents. When a T killer cell detects the viral protein by binding to it displayed on the cells MHC1, it becomes activated and will proliferate
MHC2 proteins
Only antigen presenting cells have these. These APCs include macrophages and B cells. Their role is to phagocytize particles or cells, chop them up, and display fragments using the MHC2 display system which T helpers then recognize. After a T helper is activated by antigen displayed in MHC2, it will activate B cells and stimulate proliferation of T killer cells that are specific for the antigen. Activated B cells mature into plasma cells and secrete antibodies specific for the anigen.
BOne marrow
Site of synthesis of all the cells of the blood from a common progenitor
Spleen
filters the blood and is a site of immune cell interactions also destorys aged RBCs
Thymus
Site of T cell maturation. Shrinks in size in adults
Tonsils
masses of lymphatic tissue in the back of the throat that help catch pathogens which enter the body through respiration or ingestion
Autoimmunity
Immune system will only recognize and destroy foreign antigens. Production of many B cells and T cells is random and so they must go through a selection process to eliminate any self-reactive cells. For B cells this occurs in bone marrow but can also occur in lymph nodes. An immature B cell whose surface receptor binds to normal cell surface proteins induced to die through apoptosis. Those whose surface receptors bind to normal soluble proteins become unresponsive or anergic
T cells occurs in the thymus or in lymph nodes. Immature T cells whose antigen receptors bind normal proteins become anergic.
Ventilation
Simple movement of air into and out of lungs
Respiration
Actual exchange of gases
Conduction zone
Parts of the respiratory system that participate only in ventilation
Respiratory Zone
Parts that participate in actual gas exchange
Lungs pH regulation
In blood CO2 converted to carbonic acid by carbonic anhydrase. When CO2 is exhaled by lungs, amount of carbonic acid in the blood is decreased and as a result the pH of the blood increases (become more alkaline).
Hyperventilation
Causes alkalinization of the blood (respiratory alkalosis)
Hypoventilation
Causes acidification of the blood (respiratory acidosis)
Lungs Thermoregulation
Breathing can result in significant heat loss. Occurs through evaporative water loss. Liquid water absorbs heat as it changes into water vapor and this heat is removed from body during that process
Lungs protection from disease
Lungs provide a moist surface where chemicals can do harm. Mucociliary escalator and alveolar macrophages protect us from harmful inahled particles
Pathway of inhaled air
Nose -> Nasal cavity -> pharynx -> larynx -> trachea -> bronchi -> terminal bronchioles -> respiratory bronchioles -> alveolar ducts -> alveoli
Nose
Important for warming, humidifying, and filtering inhaled air
Nasal hairs and sticky mucus
act as filters
Nasal Cavity
An open space within the nose
Pharynx
Throat at the bottom of which is the larynx
Larynx
Made entirely of cartilage and keeps the airway open, contains epiglottis which seals the trachea during swallowing to prevent entry of food, contains vocal cords which are folds of tissue positioned to partially block flow of air and vibrate producing sound
Trachea
passageway which must remain open to permit air flow. Rings of cartilage prevent its collapse. Branches into primary bronchi each of which supplies one lung. Collapse is prevented by small plates of cartilage. Small bronchi are called bronchioles
Bronchioles
walls made of smooth muscle which allows diameter to be regulated to adjust airflow into the system
Alveolus
Actual structure across which gases diffuse
Alveoli
tiny sacs with very thin walls that are only one cell thick except where capillaries pass across its outer surface
Alveolar duct
walls are made entirely of alveoli and branches off a respiratory bronchiole
Respiratory Bronchiole
Tube made of smooth muscle just like the terminal bronchioles but has few alveoli scattered in its walls. This allows it to perform gas exchange so it is part of the respiratory zone
Respiratory Epithlium
Lined by epithelial cells. From the nose all the way to the bronchioles, they are tall columnar shaped cells. They are too thick to assist in gas exchange so they provide a conduit for air. Some specialized to secrete sticky mucus and are called goblet cells. The columnar cells of the upper respiratory tract have cilia on their apical surfaces which sweep mucus toward pharynx where it is inhaled (mucociliary escalator)
Gas Exchanging cells
Tall columnar cells too large to permit rapid diffusion so these surfaces are lined by simple squamous cells. Also can’t have mucus covering gas exchange surface so alveolar macrophages fulfill this role of protection from disease and inhaled particles
Surface tension
force created with tendency of water molecules to clump together that causes wet hydrophilic surfaces to stick together in the presence of air (hydrophobic). Wax destroys surface tension
surfactant
Alveoli are as fine and delicate as tissue paper and they tend to collapse due to surface tension. Problem solved by a soapy substance (surfactant) which coats alveoli and reduces surface tension. It is a complex mixture of phospholipids, proteins, and ions secreted by cells in the alveolar wall
Pulmonary ventilation
Circulation of air into and out of the lungs continually to replace the gases in the alveoli with those in the atmosphere
Inspiration
-drawing of air into the lungs; active process driven by the contraction of the diaphragm which enlarges the chest cavity and lungs drawing air in
-Caused by muscular expansion of the chest wall which draws the lungs outward (expanding) and causes air to enter system.
-Lungs expand due to negative pressure in pleural space driven by contraction of the diaphragm which is below the ribs between the abdomen and the chest cavity. When it contract the diaphragm flattens and draws chest cavity downward forcing it and the lungs to expand. External intercostal muscles between the ribs also contract pulling ribs upward and expanding chest cavity
The pressure in the alveoli becomes negative
air enters lung and alveoli
expiration
movement of air out of the lungs; passive expiration driven by the elastic recoil of the lungs and does not require active muscle contraction
-When diaphragm and rib muscles relax, elastic recoil of lungs draws chest cavity inward reducing the volume of the lungs and pushing air out of the system into the atmosphere. During exertion or when a more forcible exhalation is required, contraction of abdominal muscles helps expiration by pushing upward on the diaphragm further shrinking the size of the lungs and forcing more air out. Forced expiration (active process)
Pleura
Each lung is not directly connected to the chest wall but is surrounded by membranes or pleura
Parietal pleura
Lines the inside of the chest cavity
Visceral pleura
Lines the surface of the lungs
Pleural space
between the two pleura; narrow space; pressure here is negative meaning tht the two pleural membranes are drawn tightly by a vacuum. This negative pressure keeps the outer surface of the lungs drawn up against the inside of the chest wall. A thin layer of fluid between the two pleura helps hold them together through surface tension
If the pleural space is punctured what would happened
Air will leak into the pleural space (in order to equalize it with the pressure of the atmosphere
Spirometry
Measurement of the volume of air entering or exiting the lungs at the various stages of ventilation measured by spirometer
Tidal volume
Amount of air that moves in and out of the lungs with normal light breathing and is equal to about 10 percent of the total volume of the lungs
Expiratory reserve volume
Volume of air that can be expired after a passive resting expiration
Inspiratory reserve volume
Volume of air that can be inspired after a relaxed inspiration
Functional residual capcity
Volume of air left in the lungs after a resting expiration
Inspiratory Capacity
The maximal volume of air which can be inhaled after a resting expiration
Residual volume
Amount of air that remains in the lungs after the strongest possible expiration
Vital capacity
Maximum amount of air that can be forced out of the lungs after first taking the deepest possible breath
Total lung capacity
The vital capacity plus the residual volume (TLC = VC + RV)
Pulmanry circulation
Deoxygenated blood in pulmonary artery gives rise to pulmonary capillaries also called alveolar capillaries. Each alveolus is surrounded by a few tiny capillaries, which are just wide enough to permit the passage of RBC’s and have thin walls to permit diffusion of gases bw blood and alveolus. Capillaries drain into venules. SMall increases in left atrial pressure have little effect on pulmonary circulation because pulmonary veins can dilate accommodating excess blood. However if pressure in left atrium increases the pressure will increase in pulmonary capillaries and blood will be forced out of the capillaries and into surrounding lung tissue (pulmonary edema)
Lymphatic system prevents pulmonary edema from developing by carrying interstitial fluid out of lungs
Henry’s Law
-Gases in the air equilibriate with gases in liquids. In order to diffuse into a cell, gas molecules from the air must dissolve into a liquid.
-The law is the amount of gas that will dissolve into liquid is dependent on the partial pressure of that gas as well as the solubility of that gas in the liquid
(O2) = Po2 x So2
Po2 is the partial pressure of oxygen in the air above the fluid
So2 is the solubility of oxygen in that liquid
In the lungs, oxygen and carbon dioxide diffuse between the alveolar air and blood in the alveolar capillaries. Driving force for the exchange of gases in the lungs is the difference in partial pressures between the alveolar air and the blood. Gases must first pass the alveolar epithelium and then through interstitial fluid and finally across capillary endothelium (three barriers form the respirator membrane)
Regulation of ventilation rate
Principal chemical stimuli that affect ventilation rate are increased Pco2, decreased pH, and decreased Po2 (with CO2 and pH being the primary regulators and O2 secondary). Variables are monitored by special autonomic sensory receptors. pH and Pco2 are connected through the carbonic acid buffer system of the blood
Peripheral chemoreceptors
Located in the aorta and the carotid arteries and monitor the Pco2, pH, and Po2 of the blood
Central Chemoreceptors
Found in the medullary respiratory control center and monitor the Pco2 and pH of the cerebrospinal fluid
Mechanical Stretching of Lung tissue
Stimulates stretch receptors that inhibit further excitatory signals from the respiratory center to the muscles involved in inspiration. Walls of bronchi contain smooth muscle that contract (bronchoconstriction) Irritation of the inner lining of the lung stimulates irritant receptors and reflexive contraction of smooth muscle prevents irritants from continuing to enter passageway. Contractile response determined by parasympathetic nerves that release ACh. During allergy attack mast cells release histamine which cause bronchoconstriction. Epinephrine opposes this causes airway smooth muscles to relax (bronchodilation)
Irriant receptors
in lung trigger coughing and bronchoconstriction when an irritating chemical such as smoke is detected
Components of nucletoides
phosphate groups, aromatic nitrogenou base, and ribose
Purine
G and A
Pyrimidines
C T U
Nucleoside
Ribose or deoxyribose with a purine or pyrimidine linked to the 1 carbon
Nucleoides
phosphate esters of nucleosides with one two or three phosphate groups joined to the ribose ring b the 5 hydroxy group
Structure of DNA
Right handed double helix held together by hydrogen bonds between bases. Two long polypeptide chains are hydrogen bonded in an antiparallel orientation. A is always H bonded to T and G is always H bonded to C
GC pair is held together by 3 bonds
AT held together by 2 bonds
Structure is also coiled. It corkscrews in a clockwise motion with the bases on the interior and the ribose/phosphate backbone on the exterior. Double helix is stabilized by can der walls interactions between the bases which are stacked upon each other
Chromosome
large pieces of linear ds-DNA.
Prokaryotic genomes
Composed of a single circular chromosome
DNA gyrase
Uses the energy of ATP to twist the gigantic circular molecule. It functions by breaking the DNA and twisting the two sides of the circle around each other. The resulting structure is a twisted circle that is composed of ds-DNA. The twists created by DNA gyrase are called supercoils since they are coils of a structure that is already coiled
Histones
Eukaryotic genome requires denser packaging to fit within the cell. they are wrapped around globular proteins called histones. After being wrapped around histones but before being completely packed away, DNA has microscopic appearance of beads on a string. The beads re called nucleosomes; they are composed of DNA wrapped around an octamer of histones
Centromere
Region of the chromosome to which spindle fibers attach during cell division. Fibers attach via kinetochores, multiprotein complexes that act as anchor attachment sites for spindle fibers. Centromeres made of heterochromatin and repetitive DNA sequences
Telomeres
End of linear chromosomes; These regions are distinguished by the presence of distinct nucleotide sequences repeated 50 to several hundred times. Usually 6-8 base pairs long and guanine-rich. Telomeres are composed of both single and double stranded DNA. Single stranded DNA is found at the very end of the chromosome and is about 300 base pairs in length. It loops around to form a knot held together by many telomere associated proteins. This stabilizes the end of the chromosome. Telomeres function to prevent chromosome deterioration and also prevent fusion with neighboring chromosomes; they function as buffers blocking the ends of chromosomes
Intergenic regions
Composed of noncoding DNA, they may direct the assembly of specific chromatin structures and can contribute to the regulation of nearby genes but many have no known function
Copy number variations
Structural variations in the genome that lead to different copies of DNA sections. Large regions of the genome can be duplicated or deleted . The specific mechanism by which this occurs is not clear, but it may be due to misalignment of repetitive DNA sequences during synapsis of homologous chromosomes in meiosis. Apply to much larger regions of genome
Tandem repeats
Short sequences of nucleotides are repeaed one right after theother from as little as 3 to over 100 times
Conservative replication
The parental ds-DNA would remain as is while an entirely new double stranded genome was created
Dispersive theory
both copies of the genome were composed of scattered pieces of old and new DNA
Semiconservative
Individual strands of the double stranded parent are pulled apart and then a new daughter strand is synthesized using the parental DNA as a template to copy from. Each new daughter chain is perfectly complementary to template
Topoisomerases
When helicase unwinds the helix at the origin of replication, the helix gets wound more tightly upstream and downstream from this point. The chromosome would get tangled and eventually break except that topoisomerases cut one or both of the strands and unwrap the helix releasing the excess tension created by the helicases
SIngle stranded DNA
Is much less stable than ds-DNA. Single stranded binding proteins protect DNA that has been unpackaged in preparation for replication and help keep the strands separated. Separated strands are referred to as an open complex. Replication can begin
RNA Primer
Must be synthesized for each template strand. Accplished by a set of proteins called the primosome of which the central component is an RNA polymerase called primase. Primer synthesis is important because the next enzyme DNA polymerase cannot start a new DNA chain from scratch. It can only add nucleotides to an exiting nucleotide chain
Prokaryotes Polymerases
DNA Pol 3: responsible for the super fast super accurate elongation of the leading strand;capable of 3 to 5 exonuclease activity (proofreading)
DNA Poly 1: Starts adding nucleotides at the RNA primer; this is 5 to 3 polymerase activity. Poor processivity. Also capable of 3 to 5 exonuclease activity (proofreading); removes the RNA primer; important for excision repair
DNA Poly2: participates in DNA repair pathways and is used as a backup for DNA poly 3; 5 to 3 polymerase activity and 3 to 5 exonuclease proofreading function
DNA Pol 4 and 5 are error prone in 5 to 3 polymerase activity but still function to stall other polymerase enzymes at replication forks when DNA repair pathways have been activated
Telomerase
An enzyme that adds repetitive nucleotide sequences to the ends of chromosomes and lengthens telomeres. Telomerase contains an RNA primer and reverse transcriptase enzyme
Inmost organisms, telomerase only expressed in germ line, embryonic stem cells, and some WBC’s
PHysical mutagens
ionizing radiation such as x rays, alpha particles, and gamma rays can cause DNA breaks. IF these only occur on one strand, they can be easily patched up because the DNA helix is still held together into one piece
UV light
causes photochemical damage to DNA. IF two pyrimidines are beside each other on a DNA backbone UVA light can cause them to become covalently linked. These primidine dimers distort the DNA backbone and can cause mutations during DNA replication if they are not repaired
Transposons
Both prokaryotes and eukaryotes have mobile genetic elements; transposons can cause mutations and chromosome changes such as inversions, deletions, and rearrangement
IS element: composed of a transposon gene flanked by inverted repeat sequences
-All tranposons contain a gene that codes for a protein transposase. This enzyme has cut and paste activity where it catalyzes mobilization of the transposon and integration into a new genetic location. Sometimes transposon is completely excised and moved and sometimes it is duplicated and moved while still maintained at the original location
-Many mobilizations have not effect because the transp
oson inserts into a relatively unimportant part of the genome. Transposons can cause mutations if they jump into an important part of the genome
-They can insert into any part of the genome and this can affect gene expression or cause mutations. They can jump into a promoter and turn gene expression off
-Can also cause structural changes to chromosomes when they work in pairs
Directionality of the transposon
If a chromosome has two transposons with the smae direction the transposon can line up beside each other so they are parallel. This causes the chromosomal segment between them to loop around. Recombination occurs be the tranposons. The original chromosome completely loses the DNA segment between the transposon. Segment of DNA that is lost takes one transposon with it meaning it can jump back into the genome elsewhere causing chromosome rearrangement
In born errors of metabolism
Huge group of genetic diseases that involve disorders of metabolism. Most of these are due to a single mutation in a single gene that codes for some sort of metabolic enzyme. Symptoms are caused by either the build up of a toxic compound that can’t be broken down or by the deficiency of an essential molecule that cannot be synthesized
Homology Dependent Repair
Repair pathways that rely on characteristic of DNa being double stranded so that mutations on one strand of NA can be repaired using the undamaged complementary information on the other strand. Can be divided into before DNA replication (excision repair) and after DNA replication (post replication repair)
Excision repair
involves removing defective bases or nucleotides and replacing them. IF these base are not repaired they can induce mutations during DNA replication since replication machinery cannot pair them properly
Post replication repair
Targets mismatched base pairs that were not repaired by DNA polymerase proofreading during replication. Mispaired bases must be identified and fixed.
Homologous recombination
One sister chromatid can help repair a DSB in the other. First DSB is identified and trimmed at 5’ ends to generate single stranded DNA. This is done by nucleases which break phosphodiester bonds and helicase. Many proteins bind these ends and starts a search of the genome to find a sister chromatid region that is complementary to the single stranded Dna. Once found, the complementary sequences are used as a template to repair and connect the broken chromatid. This requires a joint molecule where damaged and undamaged sister chromatid cross over.
Nonhomologous endjoining
Cells that arent’ actively growing or cycling through the cell cycle dont have the option of using sister chromatids to repair DSBs in a error free way. Since DNA replication isnt happening there is not chromosome backup to use. Even a poorly repaired chromosome is better than one with a DSB ince chromosome breaks can lead to rearrangements. Nonhomologous end joining is common in eu but not in prokaryotes. First broken ends are stabilized and processed an DNA ligase connects fragments.
Replication vs Transcription
Replication and transcription involve template driven polymerization. The driving force for both processes is the removal and subsequent hydrolysis of pyrophosphate from each nucleotide added to the chain with the existing chain acting as nucleophile. RNA polmerase has not been shown to possess the ability to remove mismatched nucleotides it lacks exonuclease acitivit so it cannot correct its errors. Transcription begins at a specific spot on the chromosome (start site) which is different from where replication begins (origin)
prokaryotic RNA polymerase
Large enzyme complex consisting of five subunits: two alpha, a beta, a beta’, and omega subunit This is the core subunit responsible for rapid elongation of the transcript. However core enzyme needs additional subunit (sigma factor) which is required to form what is sometimes referred to as the holoenzyme which is repsonsible for initiation
Prokaryotic Transcription
- Initiation occurs when RNA polymerase holoenzyme binds to a promoter. Typical bacterial promoter includes two sequences: Pribnow box at -10 adn -35 sequence. Holoenzyme scans the chromosome until it recognizes a promoter and then tops forming a closed complex
- RNA poly bound at promoter with a region of single stranded DNA is open complex and transcription can begin.
- Sigma factor helps polymerase to find promoters. The first it increases ability for RNA poly to recognize them and decreases the nonspecific affinity of holoenzyme for DNA
- Core enzyme elongate RNA chain processively . As the core enzyme elongates it moves along the DNA downstream in a transcription bubble
Prokaryotic and Eukaryotic Transcription Location
Prokaryotes have no nucleus so transcription occurs free in the cytoplasm in the same compartment where translation occurs and they occur simultaneously
Primary transcript in prokaryotes is mRNA. Product of transcription is ready to be translated. But the eukaryotic primary transcript is hnRNA and is modified extensively before translation (cutting off exons)
Introns
intervening sequences that are removed before RNA is translated
Spliceosome
Mediates splicing; complex contains over 100 proteins and 5 small nuclear RNA molecules; snRPS recognize and hydrogen bond to conserved nucleotides in the intron typically GU at the 5’ end, AG at the 3’ end .
Alternative splicing
Different options or patterns of splicing. One gene could have different promoters in the 5’ region which can change where/how the RNA begins.
Eukaryotic hnRNA modifications
These occur before trnalstion can happen
1. 5’ cap: methylated guanine nucleotide stuck on the 5’ end. Essential for translation
2. A 3’ poly A tail: string of several hundred adenine nucleotides.
Cap and poly-A tail are important in preventing digestion of the mRNA by exonucleases that are free in the cell
RNA Poly 1
Transcribes most rRNA
RNA Poly 2
Transcribes hnRNA (so ultimately mRNA), most snRNA, and some miRNA
RNA Poly 3
Transcribes tRNA, long ncRNA, siRNA, so miRNA, and a subset of rRNA
Translation
Synthesis of polypeptides according to the amino acid sequence dictated by the sequence of codons in mRNA. mRNA molecule attaches to a ribosome at a specific codon and the appropriate amino acid is delivered by a tRNA molecule. Then the second amino acid is delivered by another tRNA. Then eh ribosome binds the two amino acid together creating a dipeptide
transfer RNA
Composed of a single transcript produced by RNA poly 3. Tertiary structure of every tRNA molecule is similar. tRNA have a stem and loop structure stabilized by hydrogen bonds between bases on neighboring segments of the RNA chain. One end of the structure is responsible for recognizing the mRNA codon to be translated. This is the anticodon, a sequence of three ribonucleotides which is complementary to the mRNA codon the tRNA translates. Keys tep is specific base pairing between the tRNA anticodon and the mRNA codon. Dictates which amino acid will be added. The other end of the the tRNA molecule has the amino acid acceptor site which is where the amino acid is attached to the tRNA
Amino acid activation
tRNA loading: reaction coupling. Two energy high phosphate bonds are hydrolyzed to provide the energy to attach an amino acid to its tRNA molecule
Useful because breaking the aminoacyl t-RNA bond will drive peptide bond formation
1. amino acid is attached to AMP to form aminoacyl AMP. Nucleophile is acidic oxygen of aa and the leaving group is PP
2. Prophosphate leaving group is hydrolyzed to 2 orthophosphates. This reaction ishighly favorable
3. tRNA loading, an unfavorable reaction is driven foreward by the destruction of the high energy aminoacl
requires two atp equivalents because it uses two high energy bonds
Aminoacyl tRNA synthetase enzymes
Specific to each amino acid and there is at least oen amino acyl tRNA synthetase for every amino acid. Recognizes both the tRNA and the amino acid bsed on their three dimenstional structures
Eukaryotic and Prokaryotic Ribosome
Pro: 70S; Composed of 30S small subunit (16S rRNA and 21 peptides) and a 50S large subunit (23S and 5S and 31 peptides)
Eu: 80S; large (3 rRNA molecules 5S, 5.8S, and 28S and 46 peptides and sediments in a gradient at a rate of 60S) small has 33 peptides and one rRNA 18S
23S rRNA in pro and the 28S rRNA in eu have ribozyme function and help amino acids during protein synthesis via peptidyl transferase activity contributes to peptide bond formation
Binding sites in amino acids
A site: where each new tRNA delivers its amino acid
P site: where the growing polypeptide chain still attached to a tRNA is located during translation
e site: a now empty tRNA sits prio to its release from the ribosome
A -> P -> E
Initiation in prokaryotes
No promoter but instead a Shine Dalgarno sequence
1. Small ribosomal subunit 30S binds two initation proteins called IF1 and IF3. This complex then binds the mRNA transcript
2. aminoacyl-tRNA joins along with a third initiation factor (IF2) which is also bound to one GTP
3. The 50S subunit completes the complex
Process powered by the hydrolsis of one GTP molecule. First aminoacyl tRNA is special (initiator tRNA called fMet-tRNA) Initiator tRNA sits in the P site of the 70S ribosome hydrogen bonded with the start codon
Elongation Prokaryotes
- A second aminoacyl tRNA enters teh A site and hydrogen bonds with the second codon. This requires the hydrolysis of one phoshpate from GTP. Elongation factor is called Tu which is a GTPase
- Second elongation factor EF-Ts removes the remaining GDP from Ef-Tu. Peptidyl transferase activity of large ribosomal subunit 23S catalyzes the formation of a peptide bond between fMet and second amino acid. Then translocation in which tRNA 1 now empty moves into the E site, trna 2 holding the growing peptide moves into the P site and the next codon to be translated moves into the A site. Elongation factor EF-G helps with translocation
Termination Prokaryotes
Occurs when a stop codon appears in the A site. Instead of a tRNA a release factor now enters the A site. This causes peptidyl transferase to hydrolyze the bond between the last tRNA and the completed polypeptide.
Prokaryotes have 3 release factors which mediate translation termination b recognizing stop codons
1. RF1 recognizes termination codons UAA and UAG
2. RF2 recognizes UAA and UGA
3. RF3 is a GTP binding protein that doesn’t recognize a stop codon but leads to the dissociation of RF1/RF2 after peptide release
Eukaryotic Translation
- Begins with formation of the initiation complex. First a 43S preinitiation complex forms composed of the 40S small ribosomal subunit, Met-tRNA and several proteins
- Next complex is recruited to the 5’ capped end of the transcript by an initiation complex of proteins
- INitiation complex starts scanning the mRAN from the 5’ end looking for a start codon and then the large ribosomal subunit 60S is recruited and transltion begins
- eIF3 binds the small ribosomal subunit and prevent sit from prematurely associating with the 60S subunit
- eIF4A is a helicase and unwinds mRNA
- eiF4E binds the 5’ cap of the mRNA and eIF4G is a scaffold protein
Activity of EIF proteins is controlled by post translational modification such as phophorylation
eEF-1 subunits
One that helps with entry of an amino acyl tRNA into the A site and one that is a guanine nucleotide exchange factor catalyzing the release of GDP
Eukaryotic translocase is eEF-2
cap-independent translation
Eukaryotes are capable of starting translation in the middle of an mRNA molecule. The transcript must have an internal ribosome entry site. IREs make sure the cell can make essential protein when under sub-optimal growth conditions. Cells under stress generally inhibit translation and cap-independent translation allows the cell to make proteins when doing so is crucial for survival or programmed cell death
How does DNA methylation turn off eukaryotic gene expression?
- Methylation physically blocks the gne from transcriptional proteins
- Certain proteins bind methylated CpG groups and recruit chromatin remodeling proteins that change the winding of DNA around histones
Imprinting
When only one allele of a gene is expressed. In some situations, the maternal allele is expressed an inothers the paternal allele is expressed. Imprinted genes tend to be clustered together on chromosomes.
Primary method of regulation of gene expression in prokaryotes
- Regulation of transcription. some promoters are stronger than others but problem is that mechanism is preset and cant respond to changing conditions in cell.
- Transcription of enzymes in bioosynthetic pathways should be inhibited by their product
- Transcription of enzymes involved in catabolic pathways should be automatically inhibited whenever the substrate is not around and activated when it is
Repressible
Anabolic enzymes whose transcription is inhibited in the presence of excess amounts of product
Inducible enzymes
Catabolic enzymes whose transcription can be stimulated by the abundance of a substrate
lac operon
-Inducible since enzymes it codes for are part of lactose catabolism
-Components
1. P region: promoter site on DNA to which RNA polymerase binds to initiate transcription of Y, Z, and A genes
2. O region: operator site to which Lac repressor binds
3. Z gene: codes for enzyme B galactosidase which cleaves lactose into glucose and glactose
4. Y gene: codes for permease, a protein which transports lactose into the cell
5. A gene: codes for transacetylase an enzyme which transfers an acetyl group from acetyl-CoA to B galactosidase
Two genes each eith their own promoter that code for proteins
1. crp gene: located at a distant site, this gene codes for a catabolite activator protein (CAP) and helps couple the lac operon to glucose levels in teh cell
2. I gene: located at a distant site, this gene codes for the Lac represoor protein
Components of operon
coding sequence for enzymes and upstream regulatory sequences or control sites
Bacterial cells source of energy
Use glucose. In the presence of glucose, the lac operon will be off or expressed at low amounts. Mediated by teh CAP and repressor proteins. Glucose levels control a protein called adenylyl cyclase which converts ATP to cAMP. In high glucose conditions, adenylyl cyclase is inactivated and cAMP levels are very low. In low levels, the opposite is true. CAP binds cAMP and this binds the promoter of the lac operon which helps activate RNA poly at the lac operon and contribute to operon being turned on when glucose levels are low
I gene
codes for a repressor protein which binds the operator of the lac operon. This prevents RNA pol from binding the promoter and transcribing z Y and A genes blocking tanscription of the operon when lactose is absent. Repressor can bind lactose and this blocks its acitivit on the operator. This binding is allosteric causing a conformational change in tertiar structure of the repressor protoin so that is is no longer cpable of binding to the operator and then falls of f the DNA
High transcription of Z, Y, and A genes
Occurs when glucose is absent and lactose is present. Lwo glucose results in an increased amount of cAMP which binds to CAP and helps activate RNA polymerase activity at the Lac operon. latose presence means lav repressor is unable to bind the lac oeprator and negatively regulate trnascription and so the mRNA is transcribed at high levels. When level sof lactose become scarce there isnt enought to bind to rhe represoors and most of hte repressor proteins return to their original strucuter and noe rebind their operator decreasing transcirption of these genes
RNA translocation
mRNA transcripts must be exported from the nucleus to the cyplasm and can also be taken to othe areas of the cell. They are translationally silent when this is happening.
mRNA surveillance
Cells closely monitor mRNA molecules to ensure that only high quality mRNA transcripts are read by the ribosome. Defective transcripts and stalled transripts are degraded
RNA interference
way to silence gene xpression after a transcript has been made. It is mediated by miRNA and siRNA
Protein folding
Chaperones, family of proteins, that fold protein into correct 3D shape. If folded correctly the protein is said to be in its native conformation
Liver
- Responsible for excreting many wastes by chemically modifying them and releasing them into bile
- deals with hydrophobic or large waste products which cannot be filtered out by kidneys (kidney cn only eliminate small hydrophils dissolved in plasma)
- Synthesizes urea and releases it into the bloodstream
Urea
A carrier of excess nitrogen resulting from protein breakdown. Excess nitrogen must be converted to urea because free ammonia is toxic
Colon
Reabsorbs water and ions from feces. It doesn’t really excrete but it processes wastes already destined for excretion. Also is capable of excreting excess ions into the feces using active transport
Skin
Produces sweat which contains water, ions, and urea. Sweating not controlled by the amount of waste that needs to be excreted but by temperature and level of sympathetic nervous system activity
Kidneys
Final responsibility for excretion of hydrophilic wastes. Substances include water, sodium bicarbonate, and urea. Kidney is a sensitive regulator that must keep concentrations at optimum levels as opposed to simply dumping things
Anatomy of Urinary System
Blood enters kidney from a renal artery which is the direct branch of the lower portion of the abdominal aorta. Purified blood is returned to the circulatory system by the large renal vein which goes to inferior vena cava. Urine leaves each kidney in a ureter which empties into urinary bladder. The bladder is a muscular organ that stretches as it fills with urine. When it becomes full, signals of urgency are sent to the brain. There are two sphincters controlling release of urine from the bladder.
Anatomy of Urinary System
Blood enters kidney from a renal artery which is the direct branch of the lower portion of the abdominal aorta. Purified blood is returned to the circulatory system by the large renal vein which goes to inferior vena cava. Urine leaves each kidney in a ureter which empties into urinary bladder. The bladder is a muscular organ that stretches as it fills with urine. When it becomes full, signals of urgency are sent to the brain. There are two sphincters controlling release of urine from the bladder. An internal sphincter made of smooth involuntary muscle and an external sphincter made of skeletal voluntary muscle. The internal sphincter relaxes reflexively and the bladder contracts when the bladder wall is stretched. If a person decide the time is appropriate, they can relax the external sphincter allowing urine to flow from bladder into urethra and out of the body
Internal anatomy of the kidney
- Outer region is the cortex and inner is medulla
- Medullary pyramids are pyramid shaped striations within medulla. They appear like this because of collecting ducts. Urine empties from collecting ducts and leaves the medulla at the tip of a pyramid, known as papilla
- Each papilla empties into a space called a calyx and the calyces converge to form renal pelvis which is a large space where urine collects
- Renal pelvis empties into the ureter
Functional Unit of the Kidney
Is the nephron and consists of 2 components
- a rounded region surrounding capillaries where filtration occurs (capsule)
- Coiled tube (renal tubule) that receives filtrate from the capillaries in the capsule at one end and empties into a collecting duct at the other end which them dumps urine into the renal pelvis
Filtration
- Blood from renal artery goes to afferent arteriole which branches into a ball of capillaries (glomerulus)
- Then the blood goes into an efferent arteriole. Constriction of this arteriole results in high pressure in the glomerulus which causes fluid to leak out of the glomerular capillaries.
- Fluid passes through filter called the glomerular basement and enters Bowman’s capsule. Lumen of this capsule in continuous with the lumen of the rest of the tubule.
- Substances that are too large to pas through glomerular basement membrane are not filtered and stay in the blood and drain into the efferent arteriole (blood cells and plasma proteins)
Selective reabsorption
- Filtrate in the tubule includes water and small hydrophobic molecules such as sugars and amino acids and urea. Some of these must be returned to bloodstream
- They are extracted from tubule via active transport and picked up by peritubular capillaries which drain into venules that lead to the renal vein
- Most of the reabsorption occurs in part of the tubule nearest to Bowman’s capsule called the proximal convoluted tubule. All solute movement here is accompanied b water movement and so a lot of water reabsorption occurs here (70% of volume of filtrate is reabsorbed here)
- Selective reabsorption also occurs in distal convoluted tubule and is more regulated with hormones
Secretion
Movement of substance into the filtrate via active transport thus increasing the rate at which they are removed from the plasma. This is a back up method to ensure that what needs to be eliminated gets eliminated. Secretion occurs all along the tubule most secretion takes place in DCT and CD
Concentration and Dilution
Before filtrate is discarded into ureter as urine adjustments are made so that urine volume and osmolarity are appropriate. This occurs in distal nephron which includes DCT and the CD. Controlled by ADH and aldosterone
ADH
When you are dehydrated, there is low volume of fluid in bloodstream and high solute concentration. So you need to make small amounts of highly concentrated urine. Then ADH is released by post. pituitary and prevents water loos in urine by inc water reabsorption into distal nephron which is done by making it permeable to water. Without DH this area is not permeable to water. Water then flows out of filtrate into tissue of kidney where it is picked up by peritubular capillaries and returned to the blood. After drinking a lot of water plasma volume is too high and large volume of dilute urine is necessary. So no ADH is secreted and so the collecting duct is not permeable to water and so any water in filtrate remains in tubule and is lost in the urine
Microscopic Anatomy and Function of Nephron
Bowman’s capsule empties into first part of tubule (PCT). Both BC and PCT are located in renal cortex. PCT empties into loop of Henle which is a long loop that dips down into renal medulla. Part that heads into medulla is the descending limb and the part that heads out is the ascending limb. Descending limb is thin walled but ascending is thick. Loop of Henle becomes the DCT which dumps into a CD which merge to form larger tributaries which empty into renal calyces
Structural difference between thick portion of tubule and thin
Thin made of squamous epithelial cells which are not very metabolically active but thick are made of cuboidal which are large thick cells busily performing active transport
Loop of Henle
- Countercurrent Multiplier
- Descending limb is permeable to water but not ions so water exits the limb flowing into the high osmolarity medullary interstitium so the filtrate is concentrated
- Thin ascending limb is not permeable to water but passively loses ions from the high osmolarity filtrate into the renal medullary interstitium. Thick ascending limb actively transports salt out of the filtrate into the medullary interstitium and the medullary interstitium becomes very salty
Vasa Recta
Forms a loop that helps to maintain the high conc of salt in the medulla. The ascending portions of the vasa recta are near the descending limb of the loop of Henle and thus carry off the water that leaves the descending limb. Vasa recta are branches of efferent arterioles. V.R. are eager to reabsorb water bc the blood is like coffee grinds that have been drained. VR returns to the bloodstream any water that is reabsorbed from filtrate and performs countercurretne xchange
Renal Regulation of BP
Glomerular filtration rate depends directly on pressure kidney has mechanisms to regulate BP
1. Juxtaglomerular Apparatus (JAG)
JAG
A specialized contact point bw the afferent arteriole and the distal tubule. Here the cells are called juxtaglomerular cells and those in distal tubule are macula densa. JG cells are baroreceptors that monitor systemic BP. Cells of macula densa are chemoreceptors and monitor filtrate osmolarity in the distal tubule. When filtrate osmolarity dec the cells of the macula densa stimulate the JG cells to release renin. The macula densa also causes a direct dilation of the afferent arteriole inc blood flow to and thus BP and filtration rate in the glomerulus
Renal Regulation of pH
When plasma pH is too high, HCO3- is excreted in the urine; when plasma pH is too low, H+ is excreted
- Enzyme: carbonic anhydrase involved and found in epithelial cells throughout the nephron except the flat squamous cells of the thin parts of the loop of Henle
- Carbonic anhydrase catalyzes conversion of CO2 into carbonic acid which dissociates into bicarbonate plus a proton then the kidney can reabsorb or secrete bicarbonate or protons as needed
- Renal pH adjustments are slow and require several days to return plasma pH to normal but lung can also help regulate
- By exhaling excess CO2, the lung removes an acid (H2CO3) from the blood thus raising the pH
How is digestion accomplished?
Enzymatic hydrolysis
GI tract
long, muscular tube extending from the mouth to the anus.
Tube is derived from the cavity produced by gastrulation during embryogenesis
Anus is derived from the blastopore
Inside of the gut is the GI lumen which is continuous with the space outside the bod
The GI lumen is a compartment where the usable components of foodstuff are extracted, while waste are left to be excreted as feces
GI epithelium
Because it is exposed to substances from the outside world, lumen is lined with epithelial cells that are attached to a basement membrane. The surface of the epithelial cell which faces into the lumen is the apical surface. In the small intestine, apical surfaces of these cells have outward folds of their plasma membrane called microvilli to increase their SA. Apical surface is separated from the remainder of the cell surface by tight junctions which are bands running all the way around the sides of epithelial cells creating a barrier that separates body fluids from the extracellular environment. The ides and bottom of an epithelial cell form the surface opposite the lumen known as the basolateral surface. Specialized epithelial cells are responsible fro most of the secretory activity of the GI tract
GI smooth muscle
-Two layers of smooth muscle lining the gut. Longitudinal layer runs along the gut lengthwise and the circular layer encircles it
GI motility
refers to the rhythmic contraction of GI smooth muscle and is determine by interplay of factors including
- It contracts without external stimulation
- Functional syncytium so when one cell has an action potential and contracts the impulse spreads to neighboring cells
- Has its own nervous system (enteric nervous system)
- Gi motility can be incr/decr by hormonal input
- Parasympathetic stimulates motility and causes sphincters to relax allowing passage of food through the gut while sympathetic stimulation does the opposite
Purpose of GI motility
Mixing of food and movement of food down the gut. Mixing accomplished by disordered contractions of smooth muscle resulting in churning motions. Movement is caused by peristalsis (ordered form of contraction) In peristalsis contraction of circular smooth muscle at point A prevents food located at point B from moving backward
Bolus
A ball of food moving through the GI tract
Enteric Nervous System
Branch of the autonomic nervous system that helps to control digestion via innervation of the GI tract, pancreas, and gallbladder. It helps to regulate local blood flow, gut movements, and the exchange of fluid from the gut to and from its lumen. this branch can operate independently of the other two branches of the autonomic nervous system
Made up of two networks of neurons: the myenteric plexus and the submucosal plexus
Myenteric plexus
Found between the circular and longitudinal muscle layers and helps primarily to regulate gut motility
Submucosal plexus
Found in the submucosa and helps to regulate enzyme secretion, gut blood flow, and ion/water balance at the lumen
GI secretion
stimulated by food in the gut and by the parasympathetic nervous system and is inhibited by sympathetic stimulation. Two types of secretion: endocrine and exocrine
Exocrine composed of specialized epithelial cells organized into sacs called acini which secrete products which pass into ducts
Exocrine secretion
Performed by exocrine glands within special digestive organs. These glands release enzymes into ducts that empty into the GI lumen. Organs include the liver, gallbladder, and pancreas. Some exocrine secretion is performed by specialized individual epithelial cells in the wall of the gut. These cells are miniature exocrine glands releasing secretions directly into the gut lumen
Goble Cells
Found along the entire GI tract
Endocrine secretion
Also accomplished by both specialized organs (pancreas) and by cells in the wall of the gut. Do not empty into ducts but are picked up by nearby capillaries
Mouth
- Fragmentation: accomplished by mastication. The incisors (front teeth) are for cutting, cuspids (canine teeth) are for tearing, molars are for grinding
- Lubrication and some enzymatic digestion: Accomplished by saliva, a viscous fluid secreted by salivary glands. Saliva contains salivary amylase (ptyalin) which hydrolyzes starch breaking it into fragments. Smallest fragment yielded is disaccharide digestion to monosaccharides occurs only at the intestinal brush border. Saliva contains ligual lipase for fat digestions. Saliva also contains lysozyme which attacks bacterial cell walls thus participating in innate immunity
Pharynx
Contains the openings to two tubes: trachea and the esophagus
Trachea
Cartilage lined tube at the front of the neck which conveys air to and from the lungs
Esophagus
A muscular tube behind the trachea which conveys food and drink from the pharynx to the stomach
Epiglottis
During swallowing, solids and liquids are excluded from the trachea by this flat cartilaginous flap
Muscular rings that regulate movement of food through the esophagus
upper esophageal sphincter is near the top of the esophagus and the lower esophageal sphincter (aka cardiac sphincter) is at the end of the esophagus near entrance to stomach to prevent reflux from stomach into the esophagus
Stomach
Purposes include: partial digestion of food, regulated release of food into small intestine, and estruction ofmicroorganisms
Acidity
pH about 2 due to secretion of HCl by parietal cells located in the gastric mucosa. Effects include destruction of microorganisms, acid catalyzed hydrolysis of many dietary proteins, and conversion of pepsinogen to pepsin
Pepsin
Enzyme secreted by chief cells in the stomach wall and catalyzes protein breakdown. Secreted as pepsinogen which is an inactive precursor that must be converted to the active form (pepsin). Conversion catalyzed by gastric acidity. Inactive form is a zymogen that are activated by proteolysis
Motility
Churning of food breaks up food particles so they are exposed to gastric acidity and enzymes. Food mixed with gastric secretions is known as chyme
Sphincters
Pyloric sphincter prevents the passage of food from the stomach into the duodenum. Opening of the sphincter is (stomach emptying) is inhibited when the small intestine already has a large load of chyme. Stretching or excess acidity in the duodenum inhibits further stomach emptying by causing sphincter to contract. Hormone that mediates is cholecystokinin, secreted by epithelial cells in the wall of the duodenum
Gastrin
Hormone secreted by cells in the stomach wall known as G cells. stimulates acid and pepsin secretion and gastric motility. Secretion is stimulated by food in the stomach and parasympathetic stimulation. Histamine binds to parietal cells to stimulate acid release (secreted in response to stomach stretching and to gastrin)
Small intestine
Food leaving stomach enter here, a tube about an inch wide and ten feet long. Divided into three segments: duodenum, jejunum, and ileum. Digestion begins in the mouth continues in the stomach and is completed in the duodenum and jejunum. Absorption begins in the duodenum and continues throughout the small intestine.
Intestinal villus
Finger like projection of the wall of the gut into the lumen
- Contains capillaries which absorb dietary monosaccharides and amino acids. Capillaries merge to form veins which merges to form large hepatic portal vein which transports blood containing amino acids and carb from gut to liver
- Contains small lymphatic vessels called lacteals which absorb dietary fats
- Peyer’s patches are part of the immune system. They are collections of lymphocytes dotting the villi that monitor GI contents and confer immunity to gut pathogens and toxins
Two ducts that empty into duodenum
- Pancreatic duct which delivers digestive enzymes and bicarbonate
- Common bile duct: which delivers bile
- Go through same orifice: Sphincter of Oddi
Bile
contains green fluid containing bile acids which are made from cholesterol in the liver and are normally recycled. Stored in the gallbladder until needed
Functions: vehicle for excretion of waste products by liver and essential for digestion of fats
Duodenal enzymes
Duodenal enterokinase activates pancreatic zymogen trypsinogen to trypsin . others are not actually secreted but do their work inside or on the surface of the brush border epithelial cell. These duodenunal enzymes are brush border enzymes and they hydrolyzed the smallest carbohydrates and proteins (disaccharides) into monosaccharides and amino acids
Duodenal hormones
- The three main duodenal hormones are cholecystokinin secretin and enterogastrone. Cck is secreted in response to fats in the duodenum causes the pancreas to secrete digestive enzymes stimulates gallbladder contraction and bile release and decreases gastric motility this is Dan to cooperate fast present by digesting them and preventing further stomach emptying. Secretin is released in response to acid in the duodenum and it causes the pancreas to release large amounts of HCO3- in water this neutralizes hydrochloric acid released by the stomach
Jejunum and Ileum
substances not absorbed in the duodenum must be absorbed in lower segments of small intestine. Lower parts perform special absorptive processes.
Ileocecal valve
separates the ileum from the cecum which is the first part of the large intestine
Bacteria in colon
The coon contains lots of bacteria many of which are facultative or obligate anaerobes. Undigested materials are metabolized by colonic bacteria and can result in gas given off as a waste product of bacterial metabolism the bacteria are important because it keeps dangerous bacteria from proliferating because there’s competition for space and nutrients and bacteria Supply us with vitamin K which is needed for blood clotting
Accessory Organs
Play role in digestion but not a part of the alimentary canal (pancreas, liver, gallbladder, and large salivary glands)
Exocrine Pancreas
- Pancreatic amylase hydrolyze polysaccharides to disaccharides.
- Pancreatic lipase hydrolyzes triglycerides at the surface of a micelle
- Nucleus is hydrolyzed dietary. Pancreatic proteases are responsible for hydrolyzing polypeptides to di and tripeptides. These proteases are secreted in their inactive zymogen forms. Zymogens are activated by removal of a portion of the polypeptide chain
Controlled by CCK and secretin
Integrated roles of the liver
The liver receives oxygenated blood from the hepatic arteries and receives venous blood draining the stomach and intestines through the hepatic portal vein. As this Blood goes through the liver nutrients are extracted by hepatocytes which monitor the blood and make changes based on what is and is not present. Liver and skeletal muscles can store glucose as glycogen and break it down when it’s needed but only the liver can release free glucose to the bloodstream. Waste products from protein breakdown are regulated through the liver ammonia is toxic to the body so it is taken to the liver where it is converted to urea lipids exit the intestine and enter the lymphatic system in molecules called chylomicrons which are degraded by light pieces into triglycerides glycerol and chylomicron Remnants which are taken up by hepatocytes in combined with proteins to make lipoproteins. Many plasma proteins such as albumin and clotting factors are made in the liver and secreted into the plasma. There is also the major Center for drug and toxin detox in the body
Hormonal Control of appetite
When the stomach is empty gastric cells produce hormone ghrelin to stimulate appetite. When colon is full, the jejunum produces peptide YY. The hormone leptin is made by white adipose tissue to suppress the appetite and it is secreted in response to high triglyceride levels. All three are mediated by the arcuate nucleus of the hypothalamus
Carb Pathway
Chewing the bread increases the surface area allowing it to soak up more saliva. Ptyalin hydrolyzes starch into fragments. Tongue and cheeks form bolus. Upper esophageal sphincter relaxes. Peristalsis carries bolus to stomach. Lower esophageal spincter relaxes. in stomach strong acid destroys microorganisms and hydrolyzes and polysaccharides. Stomach churns the bread forming acidic chyme which is released into duodenum. In duodenum pancreatic amylase chops up polysaccharides into disaccharides which go into the intestinal brush border. Disaccharide formed into monosaccharides. Monosaccharides are bulky so they are taken to the intestinal epithelial cell by secondary active transport
Proteins Pathway
Food is ground and mixed with saliva. Bolus is formed and swallowed. Churning on stomach mixes food with acid, mucus, and enzymes. Acidity kills microorganisms and causes peptide bonds to hydrolyze. Activated pepsin attacks polypeptides and breaks into fragments. Chyme is released into the duodenum. Chyme in duodenal epithelial cells to release cck and secretin. Gallbladder receives concentrated bile and pancreas secretes high pH bicarbonate and digestive zymogens. Protesis continue to work on polypeptides until all that’s left is di and tripeptides. These are hydrolyzed by brush border peptidases. Secondary active transporter specific to each amino acid couples uptake of the amino acid to the entrance of sodium into the cell, and a uniporter helps movement of intestinal epithelial cell into interstitium. Amino acid in liver where it is used for energy or synthesis
Fats pathway
Triglycerides in mouth melt and are swallowed. Stomach mixes triglycerides with acid. Triglycerides are hydrophobic so they end up floating in the layer above the aqueous content and then are emptied into the duodenum where they release cck into bloodstream. Pancreas enzymes into the gut via the sphincter of oddi. But pancreatic lipase cannot digest the facts because they are organized into huge hydrophobic droplets. Cck in bloodstream stimulates gallbladder contraction which sends bile into the duodenum and emulsifies lipids forming tiny micelles. Pancreatic lipase that hydrolyzes triglycerides to monoglycerides + free fatty acids which go into the intestinal epithelial cells by simple diffusion. Then they are converted back to triglycerides and packaged into chylomicrons which are large particles of fat and protein which transport fats in the bloodstream. Please do not enter intestinal blood capillaries but they enter lymphatic capillaries known as lacteals which merge to form lymphatic vessels which empty into the thoracic duct which empties into a large vein near the heart after a few minutes large amounts of fat are released from the thoracic duct directly into the bloodstream. Chylomicron circulate throughout body and are whittled away by removal of fat lipoprotein lipase hydrolyzes chylomicron triglycerides into monoglycerides and free fatty acids which can go into adipocytes and liver cells and be stored as triglycerides.
Vitamins
Vitamins are important for diet because they cannot be made in the body. Divided into fat soluble and water soluble. Fat soluble vitamins require bile acids for solubilization and absorption. Excess fat soluble vitamins are stored in adipose tissue. Excess water soluble vitamins are excreted in urine by the kidneys
Fat soluble vitamins
Vitamin A, D, E K
Water soluble vitamins
B1, B2, B3, B6, B12, C, Biotin, FOlate
Vitamin A
A visual pigment that changes conformation in response to light. It is important for blood clotting factors.
Vitamin D
stimulates calcium absorption from the gut and helps control calcium deposition in Bones.
Vitamin E
prevents oxidation of unsaturated fats.
Vitamin K
It is important for blood clotting factors.
Vitamin B1
needed for enzymatic decarboxylation
Vitamin B2
made into fad an electron transporter
Vitamin B3
made into NAD+ an electron transporter
Vitamin B6
a coenzyme involved in protein and amino acid metabolism
Vitamin B12
involved in reduction of nucleotides to deoxynucleotides
Vitamin C
important for collagen formation
Folate
required for normal fetal nervous system development.
Biotin
prosthetic group important for transfer of carbon dioxide groups
Scrotum
a bag of skin containing the testes
Testes
The testes have two roles including: synthesis of sperm and secretion of male sex hormones including androgens (testosterone) into the bloodstream.
Site of spermatogenesis
The site of spermatogenesis within the testes are the seminiferous tubules. The walls of the tubules are formed by cells called sustentacular cells. These cells protect and nurture the developing sperm. The tissue between the seminiferous tubules is the testicular interstitium. Cells found here are the interstitial cells also called leydig cells and are responsible for Androgen or testosterone synthesis. The seminiferous tubules empty into the epididymis which is a long coiled tube located on the back of each testicle. The epididymis empties into a ductus deferens which leads to the urethra the tube inside the penis. To get to the urethra the ductus deferens leaves the scrotum and follows a particular path: Enters the inguinal Canal a tunnel that travels along the body wall toward the crest of the hip bone. From there the inguinal canal, the ductus deferens enters the pelvic cavity. In the back of the urinary bladder it joins the duct of the seminal vesicle to form the ejaculatory duct which joins the urethra. The urethra exits the body via the penis.
Semen
Seminal vesicles secrete about 60% of the semen. Is a highly nourishing fluid for sperm and is produced by the seminal vesicles the prostate and the bulbourethral glands.
Penile Erection
Penile erection facilitates the deposition of semen near the opening of the uterus during intercourse. Specialized erectile tissue allows erection. That is composed of modified veins and capillaries surrounded by a connective tissue sheet. Erection occurs when blood accumulates at high pressure in the erectile tissue. Three compartments contain erectile tissue including the corpora cavernosa which there are two and the Corpus spongiosum which there is only one.
Seminal vesicles, prostate gland, and bulbourethral glands secretion and function
The seminal vesicles secrete mostly fructose. Secretion is nourishment of sperm. Gland secretes mostly fructose and a coagulant and the function is nourishment. Bulbourethral glands secrete thick alkaline mucus which functions to lubricate the urethra and neutralize acids and male urethra and and female vagina.
Male Sexual Act
Male sexual act includes three phases including arousal orgasm and resolution. These events are controlled by an integrating Center in the spinal cord which response to physical stimulation and input from the brain.
Arousal
Arousal is dependent on parasympathetic nervous input. There are two stages erection and lubrication. Erection involves dilation of arteries supplying erectile tissue. Causes swelling which obstructs venous outflow. This causes erectile tissue to become pressurized with blood. Lubrication is the second stage. The bulbourethral gland secrete a viscous mucus which serves as a lubricant.
Orgasm
Stimulation by the nervous system is required for orgasm which includes two stages: emission and ejaculation. Emission refers to the propulsion of sperm from the ductus deferens and semen from the accessory glands into the urethra by contractions of smooth muscle. Ejaculation follows in which semen is propelled out of the urethra by contractions of muscles.
Resolution
Resolution is a return to normal unstimulated state. Controlled by the sympathetic nervous system it is caused by the constriction of the erectile arteries. This results in decreased blood flow to the erectile tissue and allows the veins to carry away the trapped blood.
Gametogenesis
- Involves meiosis
- Is the process where diploid germ cells undergo meiotic division to produce haploid gametes
- The gametes produced by the male are known as spermatozoa or sperm while females produce ova or eggs. Fusion is known as syngamy and it results in a zygote.
Spermatogenesis
It begins at puberty and occurs in testes throughout the adult life. The seminiferous tubule is the site of spermatogenesis. Process occurs with the aid of specialized sustentacular cells found in the wall of the seminiferous tubule. Immature sperm precursors are found in the outer wall of the tubules and nearly mature spermatozoa are deposited into the lumen where they’re taken to the epididymis. Those that give rise to spermatogenesis are known as germ cells.
Spermatogenesis
It begins at puberty and occurs in testes throughout the adult life. The seminiferous tubule is the site of spermatogenesis. Process occurs with the aid of specialized sustentacular cells found in the wall of the seminiferous tubule. Immature sperm precursors are found in the outer wall of the tubules and nearly mature spermatozoa are deposited into the lumen where they’re taken to the epididymis. Those that give rise to spermatogenesis are known as germ cells.
Final stages of sperm maturation occur in the epididymis. When they first enter, they are incapable of motility but many days later when they enter ductus deferens they are fully capable. They remain inactive due to presence of inhibitory substances secreted by ductus deferens which causes sperm to have a low metabolic rate which allows them to conserve energy and reamin fertile during storage in the ductus deferens . Spermatids develop into spermatozoa in the seminiferous tubules with the aid of sustentacular cells. DNA condenses, cytoplasm shrinks, cell shape changes so there is a head containing haploid nucleus and the acrosome and a flagellum which forms the tail There is also a neck region at he base of the tail which contains many mitochondria. The acrosome is a compartment on the head of the sperm that contains hydrolytic enzyme required for pentration of ovum’s protective layers. Bindin is a protein on the sperms surface that attaches to receptors on the zona pellucida surrounding the ovum.
Sperm precursors
- Spermatognium: Mitotically reproduce prior to meiosis and repelicate DNA in S phase of meiosis
- Primary spermatocyte: Meiosis 1
- Secondary spermatocyte: Meiosis 2
- Spermatid: Turns into a spermatozoan
- Spermatozoan: finish maturing in seminiferous tubule and epididymis
Hormonal Control of Spermatogenesis
Testosterone stimulates division of spermatogonia. LH stimulates the interstitial cells to secrete testosterone. FSH stimulates the sustentacular cells. Hormone inhibin is secreted by sustentacular cells to inhibit FSH release.
Development of the Male Reproductive System
During weeks of early development, male and female embryos are indistinguishable. Early embryos have both Wolffian ducts that can develop into male internal genitalia (epididymis, seminal vesicles, and ductus deferens) and Mullerian ducts that can develop into female internal genitalia (uterine tubes, uterus, and vagina). In absence of a Y chromosome, Mullerian duct dev’t occurs by default and female internal genitalia result. Female external genitalia (labia, clitoris) are also the default but genetic information on Y leads to development of testes which causes male internal and external genitalia to develop by producing testosterone and MIF. MIF is produced by the testes and causes regression of the Mullerian ducts. Testosterone that is responsible for deve’t of male external genitalia must be converted to dihydrotestosterone in target tissues to order its effect.
Primary estrogen proudced in ovaries
estradiol
Gonadotropin releasing Hormone
Men: LH acts on interstitial cells to stimulate testosterone production and FSH stimulates sustentacular cells.
Women: FSH stimulates granulosa cells to secrete estrogen and LH stimulates formation of corpus luteum and progeterone secretion
Female Reproductive Anatomy
The XX genotype lead sto the formation of ovaries capable of secreting the female sex hormones instead of testes that secrete androgens. In teh male testosterone causes a pair of skin folds known as labioscrotal swellings to grown and fuse forming the scrotum, In females, wihtout influence of testosterone labioscrotal swellings form labia majora of vagina. Structure that gives rise to penis becomes clitoris in female locate within labia majora in the uppermost part of the vulva. Beneath clitoris is urethral opening where urine exits the body. Surrounding urethral opening is another pair of skin folds called labia minora.
Female Sexual Act
Includes arousal, orgasm, resolution
Clitoris and labia minora contain erectile tissue and become engorged with blood just as in the male. Lubrication is provided by mucus secreted by greater vestibular glands and by the vaginal epithelium. Orgasm results in widening of the cervix. Female does not experience ejaculation
Oogenesis
Oogenesis begins prenatally. In the ovary of a female fetus germ cells divide mitotically to produce large numbers of oogonia. They’re not only undergo mitosis in utero but they also enter the first phase of meiosis and are arrested in prophase 1 as primary oocytes. These can be frozen in prophase 1 for decades until they re enter the mitotic cycle. Beginning at puberty and continuing on a monthly basis hormonal changes in body stimulate completion of the first meiotic division and ovulation. This division yields a large secondary oocyte which contains all the cytoplasm and organelles and a small polar body which contains half the DNA but no cytoplasm or organelles. The polar body remains in close proximity to the suicide. Meiotic division occurs only if the secondary oocyte is fertilized by a sperm and this division is also un equal producing a large ovum and the second polar body.
Granulosa Cells
The primary oocyte is not an isolated cell. It is found in a clump of supporting cells called the granulosa cells and the entire structure itself is called a follicle. The granulosa cells assist in maturation. An immature primary oocyte is surrounded by a single layer of a granulosa cells forming a primordial follicle. As the primordial follicle matures the granulosa cells proliferate to form several layers around the oocyte and the oocyte forms the protective layer of mucopolysaccharides termed the Zona pellucida. There may be several follicles in the ovary that are surrounded and separated by cells called thecal cells.
Graafian follicle
OF the several maturing follicles only one progresses to the point of ovulation each month; all others degenerate. During ovulation, the GF bursts, releasing the secondary oocyte with its zona pellucida and protectice granulosa cells into the fallopian tube. At this point the layer of granulosa cells surrounding the ovum is the corona radiata.
Corpus luteum
Follicular cells remaining in the ovary after ovulation form this structure
Granulosa cells secrete?
Estrogen (make and secrete) with help from the thecal cells during the first half of the menstrual cycle. Estrogen is a steroid hormone.
Ovarian Cycle
- Follicular phase: a primary follicle matures and secretes estrogen. Maturation under control of FSH. Lasts 13 days
- Ovulatory phase: Secondary oocyte released from ovary triggered b LH. Causes remnants of follicle to become corpus luteum. Day 14
- Luteal phase: full formation of the corpus luteum in ovary secretes estrogen and progestereone and has a life span of two weeks. Length 14 days
- Hormones secreted in this cycle enter the uterine cycle
Uterine Cycle
- Menstruation: triggered by degeneration of corpus luteum and drop in estrogen and progesterone levels. Decrease in these hormones causes the previous cycle’s endometrial lining to slough out of the uterus producing bleeding. Lasts 5 days
- Proliferative Phase: Estrogen produced by follicle induces proliferation of a new endometrium. Lasts 9 days
- Secretory phase: after ovulation occurs in which estrogen and progesterone produced by corpus luteum increases development of endometrium including secretion of glycogen lipids and other materials. If no preggo, the death of the corpus luteum and decline in estrogen and progesterone triggers menstruation. Lasts 14 days
LH and ovulation
Surge in LH causes ovulation. After ovulation, LH induces the follicle to become the corpus luteum and to secrete estrogen and progesterone which marks beginning of secretory phase. IF pregnancy does not occur, the combined high levels of estrogen and progesteron feedback to strongly inhibit secretion of GnRH, FSH, and LH. When LH secretion drops, the corpus luteum regresses no longer secretes estrogen or progesterone and mestruation occurs
Hormonal Changes during Pregnancy
Ovulation should be prevented so high levels of estrogen and progesterone inhibit secretion of LH preventing ovulation. The corpus luteum degenerates unless fertilization has occurred. For pregnancy, the endometrium must be maintained because it is where the embryo lives and is nourished.
Chorion
Portion of the placenta that is derived from the zygote. It secretes human chorionic gonadotropin which can take the place of LH in maintaining the corpus luteum so estrogen and progesterone can stay elevated and menstruation will not occur.
Secondary oocyte uterine tube
Ovulated secondary oocyte goes here and is surrounded by corona radiata (protective layer of granulosa cells) and the zone pellucida. The oocyte will remain fertile for about a day. If intercourse occurs, sperm deposited near cervix and are activated which involves dilution of inhibitory substances present in semen. These will survive for two or three days
Fertilization
Normally occurs in uterine tube. Sperm must penetrate corona radiata and bind to and penetrate zona pellucida. Does this by acrosome reaction. Acrosome is a large vesicle in the sperm head containin hydrolytic enzymes released by exocytosis. After corona radiata has been penetrated, acrosomal process containing actin elongates toward zone pellucida. Acrosomal process has bindin a species specific protein which binds to receptors in the zona pellucida. Sperm and egg plasma fuse. In twenty minutes, secondary oocyte completes Meiosis 2, giving rise to ootid and second polar body. Ootid matures and become ovum. Sperm and egg nuclei fuse and zygote forms.
Cleavage
Begins within hours of fertilization. Part of embryogenesis. In this stage the zygote undergoes many cell division to produce ball of cells called the morula. A cell divisions continue, morula transformed into blastocyst (blastulation). Blastocyst consists of a ring of cells called the trophoblast surrounding a cavity and an inner cell mass adhering to the inside of the trophoblast at one end of the cavity. Trophoblast will give rise to the chorion and the inner cell mass will become the embryo
Implantation
Occurs a week after fertilization. Blastocyst reaches the uterus and burrows into the endometrium. Trophoblast secretes proteases that lyse endometrial cells. Blastocyst then sinks into endometrium and is surrounded by it absorbing nutrients through trophoblast into inner cell mass and it does this until placenta develops (3 months).
Placental villi
Chorionic projections extending into the endometrium into which fetal capillaries will grow.
Amnion
Surrounds a fluid filled cavity which contains developing embryo. Amniotic fluid is the water which breaks before birth.
Allantois
develops from the embryonic gut and forms the blood vessels of the umbilical cord which transport blood between embryo and placenta
Gastrulation
Primary germ layers become distinct (ectoderm, mesoderm, and endoderm). Blastula invaginates to form layers. Inner layer is the endoderm and outer layers is ectoderm. Mesoderm develops from endoderm. In humans gastrula develops from embryonic disk instead of from a spherical blastula
Ecoderm
Entire nevous system, pituitary gland, adrenal medulla, cornea lens, epidermis of skin, nasal oral epithlium
Mesoderm
muscle bone connective tissue, cardio and lymph system blood, urogenital organs, dermis of skin
Endoderm
GI tract, GI glands, respiratory epithelium, urinary bladder
Totipotent vs pluripotent
Totipotent cells have the potential to become any cell type in the blastocyst including the trophoblast and the inner cell mass. Pluripotent cells are more specialized and can differentiate into any of the three primary germ layers and have the capacbility to become any of the 220 cell types that make up a human but not contribute to trophoblast and will not become placenta. Pluripotent differentiate into multipotent
Second trimester
Organs and organ systems continue to develop
Third trimester
Stage of rapid fetal growth including significant deposition of adipose tissue. Most of the organ systems become fully functional
Mom
Maternal respiratory rate increases to bring in additional oxygen and eliminate CO2. Blood volume increases due to a drop in oxygen levels because of the metabolic demands of the fetus and a release of erythropoietin and renin. accompanied by an increase in glomerular filtration rate. Demand of nutrients and vitamins increases by about 30%.
Parturition
Birth; dependent on contraction of muscles in the uterine wall. High levels of progesterone secreted throughout pregnancy help to repress contractions in uterine muscle but near end of pregnancy uterine excitability increases possibly due to change in ratio of hormones, presence of oxytocin and stretching of uterus and cervix
Microtubules
Hollow rod composed of two globular proteins: a tubulin and beta tubulin. They form a aB tubulin dimer. Then many dimers stick to one another noncovalently to form a sheet which rolls into a tube. Once formed the microtubule can elongate by adding aB dimers to one end. The other end cannot elongate because it is anchored to the microtubule organizing center located near the nucleus.within the MTOC is a pair of centrioles that duplicate themselves in cell division
Microfilaments
Rods formed in the cytoplasm from polymerization of the globular protein actin. The actin monomers form a chain and then two chains wrap around each other to form an actin filament. Responsible for gross movements of entire cell and amoeboid movement
Intermediate filaments
Named for their thickness which is between microtubules and microfilaments. They are heterogeneous composed of a wide range of polypeptides. They are more permanent whereas the others are disassembled and reassembled as needed by the cell
Tight junctions
form a seal between the membranes of adjacent cells that blocks the flow of molecules across the entire cell layer. They are bands running all the way across the cells.
Desmosomes
Do not form a seal but merely hold cells together. They are concise points not bands all the way around the cell. Composed of fibers that span the plasma membrane of two cells. Inside each cell, desmosome is anchored to the plasma membrane by a plaque formed by protein keratin. Not free but anchored in place by intermediate filaments of the cytoskeleton
Gap junctions
Form pore like connections between adjacent cells allowing the two cells cytoplasms to mix. Connection is large enough to permit exchange of solutes such as ions, amino acids, and carbs but not polypeptides and organelles
Pleiotropism
Its expression alters man different seemingly unrelated aspects of the organisms total phenotype
Polygenism
Complex traits that are influenced by many different genes. These traits tend to display a range of phenotypes in a continuous distribution (height)
Penetrance
Likelihood that a person with a given genotype will express the expected phenotype. Some genes have age related penetrance where the phenotype is displayed more frequently in mutation carrying individuals as they age
Epistasis
Expression of alleles for one gene is dependent on a different gene (a gene for curly hair cannot be expressed if a different gene causes baldness)
Linkage
Genes that are located on the same chromosome may not display independent assortment. Failure of genes to display independent assortment is linkage and it limits the possible combination of the alleles in the gametes
Recombination
Provides exception to linkage. During formation of gametes recombination between homologous chromosomes can separate alleles that were located on the same chromosome. Recombination produces new combinations of alleles not found in the parent and also allows genes located on the same chromosome to assort independently. Recombination occurs more frequently if genes are far apart
Recombination frequency
number of recombinants/total number of offspring
Hardy Weinberg Population Genetics
Frequencies of alleles in the gene pool of a population will not change over time provided that a number of assumptions are true 1. no mutation 2. no migration 3. no natural selection 4. no random mating 5. population is sufficiently large to prevent random drift in allele frequencies -Segregation of alleles, independent assortment, and recombination during meiosis can alter the combinations of alleles in gametes but cannot increase or decrease the frequency of an allele in the gametes of one individual or the gametes of a population p + q = 1 (p is dom and q is recessive) (p + q)^2 = 1^2 p^2 + 2pq + q^2 = 1 p^2 is the frequenc of the GG genotype 2pq is the frequency of the Gg phenotype q^2 is the frequency of the gg genotype
Directional selection
Polygenic traits often follow bell shaped curve of expression with most individuals clustered around the average and some members of a population trailing off in either direction away from the average. If natural selection removes those at one extreme the population average over time will move in the other direction (Giraffes get taller as all short giraffes die looking for food)
Divergent selection
Rather than removing the extreme members in the distribution of a trait in a population, natural selection removes the members near the average leaving those at either end. Over time divergent selection will split the population in two and lead to an new species (Small deer are selected for because they can hide and large deer are selected because they can fight but mid deer are too big to hide and too small to fight)
Stabilizing selection
Both extremes of a trait are selected against driving the population closer to the average
Artificial selection
Humans intervene in the mating of many animals and plants
Sexual selection
Animals often do not choose mates randomly but have evolved elaborate rituals and physical displays that play a key role in attracting a choosing a mate. Some birds have bright plumage to attract a mate even at the cost of increased predation
Kin Selection
Animals that live socially often share alleles with other individuals and will sacrifice themselves for the sake of the alleles they share with another individual
Species
group of organisms capable of reproudcing with each other sexually
Prezygotic barriers
Prevent the formation of a hybrid zygote
Examples:
1. Ecological: different habitats no access
2. Temporal: individuals mate at different times of day or season or year
3. Behavioral: special rituals
4. Mechanical: reproductive structures not compatible
5. Gametic: sperm from one species cannot fertilize the egg of a different species
Postzygotic barriers
Prevent the development, survival, or reproduction of hybrid individuals and thus prevent gene flow if fertilization does occur
- Hybrid inviability: offspring do not mature normally and die in the embryonic stage
- Hybrid Sterility: hybrid individual is born and develops normally but does not produce normal gametes and so is incapable of breeding
- Hybrid breakdown: when two hybrids mate successfully to produce a hybrid offspring but the second generation hybrid is biologically defective
Cladogenesis
branching speciation where one species diversifies and becomes two or more new species
Anagenesis
when one biological species simply becomes another by changing so much so that if an individual were to go back in time, it would be unable to reproduce with its ancestors
Allopatric isolation
Initiated by geographical isolation over time it leads to reproductive isolation
Sympatric speciation
occurs when a species gives rise to new species in the same geographical area such as through divergent selection
Homologous structures vs analogous structures
Homologous are physical features shared by two different species as a result of common ancestor but analogous do not share common ancestry but do share physical features
