• Aerobes - require oxygen
• Anaerobes - do not require oxygen
• Obligate aerobes - require oxygen for metabolism
• Obligate anaerobes - die in oxygen-rich environments due to production of ROS
• Facultative anaerobes - toggle between oxygen-requiring metabolism and anaerobic metabolism
• Aerotolerant anaerobes - cannot use oxygen for metabolism, but do not die in oxygenous environments

• combination of bacterial cell membrane and cell wall
• functions to provide structure to the cell, controls movement of solutes into and out of cell, and protecting the cell from intruders or a host organism's immune system

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• way of classifying bacteria by their cell walls
• initial crystal violet die is followed by a counterstain known as safranin
• envelopes that absorb the violet stain appear purple and are gram positive
• envelopes that absorb the counterstain appear pink-red and are gram negative

• bacteria that absorb violet stain and appear purple
• have cell walls containing a thick layer of peptidoglycan which is made up of amino acids and sugar
• cell walls also contain lipoteichoic acid which may activate the human immune system, but not as strongly as lipopolysaccharides

• absorb safranin counterstain and appear pink-red
• have a very thin cell wall containing peptidoglycan as well as a small space between the membrane and cell wall known as the periplasmic space
• also have outer membranes of phospholipids and lipopolysaccharides which trigger the human immune system strongly 

• plasmids - DNA acquired from external sources that is carried in smaller circular structures outside the nucleoid region
• lack of mitochondria means that the envelope is used for ETC
• contain primitive cytoskeleton
• ribosomes - contain smaller ribosomes built of 30S and 50S subunits as opposed to the 40S and 60S versions found in eukaryotes

• mode of asexual reproduction common among bacteria and archaea
• Process
  • circular chromosome attaches to cell wall and replicates as cell grows
  • plasma membrane and cell wall begin to grow inward along midline
  • two daughter cells are produced
• due to its simplicity, it is much more rapid than mitosis in eukaryotes
• limits genetic variation possible w/in population due to lack of crossing-over of two parent genomes to create genetically unique offspring

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• Despite not undergoing meiosis and genetic crossover, prokaryotes are able to transmit new genes
•  the genome is all genetic information required to create a functional bacterial cell
• Plasmids are extragenomic pieces of information that can impart beneficial traits to a bacterium
• Processes in which prokaryotes can take up new plasmids include transformation, conjugation, transduction, and transposons

• genes carried w/in plasmids capable of imparting traits that increase how pathogenic (or virulent) a bacterium is

• plasmids that are capable of integrating themselves into a bacterial genome

• method of bacterial genetic recombination
• common to gram-negative(envelope type) bacilli(rod-shaped)
• integration of foreign genetic material into the host genome (think episomes)
• most common source of genetic material is other bacteria that have lysed near a bacterium capable of transformation

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• form of bacterial sexual reproduction (gene transfer)
• unidirectional process unlike eukaryotic reproduction
  • donor male(+) bacterium forms a conjugation bridge with recipient female(-) bacterium using its sex pilus
  • unidirectionality partially imparted by lack of sex pilus in female which is imparted by sex factors passed from male(+) to female(-)

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• only genetic recombination process that requires a vector
• Process
  
  • Bacteriophage infects a host cell
  • As phage replicates using host cell's machinery, some of the cell's DNA is taken into a new phage
  • This phage infects a new bacterium, and the genetic information from the other host cell is incorporated into the new host's DNA

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• genetic elements that can insert and remove themselves from a genome at will
• if inserted w/in a coding region, it can result in disruption of the gene
• found in both prokaryotes and eukaryotes

• lag phase - bacteria enter new environment and adapt to new conditions
• exponential (or log) phase - bacteria have adapt, grow, and rapidly increase growth
• stationary phase - resources reduce in number resulting in slower reproduction and stationary colony size
• death phase - resources are depleted and bacterial colony size falls

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• genetic material - can be single-stranded or double-stranded RNA or DNA
• capsid - protein coating that holds the genetic material along with other proteins that may be necessary for viral functionality
• envelope - some viruses may have an envelope of phospholipids and proteins that is easily susceptible to heat, detergents, and desiccation making these viruses easier to kill
• bacteriophages which inject genetic material into a host cell have a tail sheath which acts as syringe and tail fibers which recognize and bind to the correct host cell.

• single-stranded RNA viruses whose genomes can be directly translated like mRNA to functional proteins by host cell ribosomes

• single-stranded RNA viruses that require synthesis of RNA strand complementary to the negative-sense RNA strand which can then act as a template for protein translation in the host cell
• these viruses must carry an RNA replicase enzyme

• enveloped, single-stranded RNA viruses that carry reverse transcriptase which converts RNA into DNA
• The DNA can then be integrated directly into the host cell's DNA
• HIV (human immunodeficiency virus) works like this

• misfolded proteins that are infectious as they lead to the misfolding of other proteins of the same type
• many times involve the change of an α-helix to a β-pleated sheet
• eventually result in protein aggregates leading to diseased state

• short circular single-stranded RNA that acts as a small pathogen
• binds to genome resulting in silencing of specific sequences and genes
• commonly known to affect plants, but there are some exceptions such as HDV (hepatitis D virus)
  • HDV alone is asymptomatic and innocuous, but in the presence of HBV, it can cause gene silencing in human hepatocytes

• form of viral infection in which host cell is kept alive to maximize its use to produce more viruses
• usually involves extrusion or release of virions through exocytosis from the plasma membrane instead of lysis

• Virus makes maximum use of the host cell to make virions until the host cell bursts due to the excessive volume of virions
• these virions can then infect other bacteria
• bacteria in this phase are referred to as virulent

• a virus that doesn't lyse the bacterium immediately may incorporate itself into the bacterial genome creating a prophage (provirus) or the predecessor to a lytic virus
• the virus is replicated as the bacterium replicates as it is part of the host genome leading to an accumulation of infected bacteria
• eventual removal of the provirus from the host genome due to environmental factors like radiation, light, or chemicals results in the bacterium entering the lytic cycle

• the life and reproduction of eukaryotic cells
• consists of interphase and M stage
• interphase is made up of G₁, S, and G₂ stages
• M stage is consists of mitosis and cytokinesis
• phases are characterized by different cellular processes and checkpoints required to move forward
• checkpoints are determined by the presence of proper proteins required to move onto the next stage
  • this is determined by cyclins and cyclin-dependant kinases (CDK's)

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• first stage of cell cycle and interphase
• known as the presynthetic gap
• organelles for energy and protein production are created
• passing into the next stage is determined by a special checkpoint referred to as the restriction point

• checkpoint between G₁ and S phases
• like other checkpoints, it is reliant on cyclins activating cyclin-dependant kinases (CDK's) to create active CDK's that can activate (phosphorylate) transcription factors for the next stage
• p53 is the main gene in control of the restriction point
• cells that do not pass the restriction point either delay division or enter the G₀ phase and leave the cell cycle

• phase outside the cell cycle
• cells are simply living and carrying out functions
• no preparations for division are made
• common example of this type of cell is the neuron
  • neurons divide when we are in utero or young and enter G₀ when we are at very young age

• known as the DNA synthesis stage (s for synthesis)
• cell replicates its genetic material for two daughter cells to each carry an entire copy of the genome
• one chromatid attached to a centromere become two sister chromatids attached to a centromere
  • ploidy doesn't change even though number of chromatids doubled

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• cell checks to ensure that enough organelles and cytoplasm is present and check that DNA replication proceeded correctly to prevent passage of mutations/errors
• acts like a checkpoint
• going from G₂ to M stage is similar to restriction point
  • also partially controlled by p53 
  • relies on presence of cyclins and CDK's

• mutations in genes may result in derangement of cell cycle and continuous, uncontrolled division
• mutations can accumulate due to continued growth and division without proper checkpoints (like restriction point) to stop cell division in the event of mutations or cell damage
• mutation in p53 gene, TP53, is most common cause as it has partial control over both checkpoints
  • improper p53 gene unable to stop cell division
• metastasis - tumors grow with continued accumulation of mutations and eventually mutations can lead to other factors encouraging the distant spread of cancer cells

• process of actual division of parent cell into two daughter cells
• occurs only in somatic cells, not cells involved in sexual reproduction (gametes)
• made up of 4 phases - prophase, metaphase, anaphase, telophase
• final step is cytokinesis which is many times grouped in
• only time during cell cycle that DNA is found as chromosomes instead of chromatin
• cells undergo a finite number of divisions before programmed death (apoptosis) - 20 to 50 times for human cells

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• first phase of mitosis
• Process
  • condensation of the chromatin into chromosomes
  • centriole (located outside nucleus in centrosome) pairs separate and move towards opposite poles of cell
  • centrioles form microtubule spindle fibers after moving to opposite ends of cell
  • nucleoli and nuclear membrane disappear
  • spindle fibers attach to kinetochores located on chromosome centromeres to make kinetochore fibers

• 2nd step of mitosis
• Process
  • centriole pairs at opposite ends of the cell
  • kinetochore fibers interact with other spindle fibers to align chromosomes at the equatorial (metaphase) plate

• 3rd step of mitosis
  • centromeres split so each chromatid has its own distinct centromere allowing sister chromatids to separate
  • sister chromatids are pulled toward opposite poles of the cell by shortening kinetochore fibers

• final steps of mitosis/M stage
• Process
  • spindle apparatus disappears, nuclear membrane reforms, nucleoli reappear, chromosomes uncoil into chromatin (telophase)
  • cytoplasm and organelles separate so that each daughter cell carries sufficient supplies for survival

• process of cell division that occurs in gametocytes instead of somatic cells
• results in the formation of 4 non-identical gametes or sex cells
• split into Meiosis I and Meiosis II
• consists of one round of replication and two rounds of division unlike mitosis

• process that occurs during Meiosis I 
• results in separation of homologous chromosomes generating 2 haploid daughter cells with non-identical genetic information

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• process that occurs during Meiosis II
• results in the separation of sister chromatids like in mitosis producing two identical gametes from a haploid cell from Meiosis I

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• distinction relevant to Meiosis I
• homologous pairs are separate chromosomes that are considered complementary to one another 
• sister chromatids are identical strands of DNA connected at the centromere to make one chromosome - not considered separate chromosomes (why ploidy doesn't change)
• 92 chromatids in mitosis makes 46 chromosomes (still diploid) and 23 homologous pairs

• Mitosis similarities
  • chromatin condenses into chromosomes
  • spindle apparatus forms
  • nucleoli and nuclear membrane disappear
• Mitosis differences
  • synapsis - homologous pairs (one paternal and one maternal chromosome) come together and intertwine at chiasmata to form a tetrad (two sets of sister chromatids)
  • crossing over - equivalent pieces of DNA exchanged between chromosomes (not sister chromatids) in tetrad at chiasmata resulting in genetic recombination

• genes tend to be inherited together based on their distance from each other on the chromosome 
  • genes that are spatially distant are less likely to be inherited together
• genetic linkage tends to be broken up by recombination through crossing over
  • genes that are spatially distant are more likely to undergo crossing over and be exchanged between homologues

• homologous pairs are aligned at the equatorial(metaphase) plate
• each chromosome in a homologous pair attaches to a separate spindle fiber at its kinetochore
  • in mitosis, each chromosome was lined up at plate and separated by two spindle fibers

• disjunction - each chromosome of paternal origin separates from its homologue of maternal origin
  • either chromosome can end up in either daughter cell - it is entirely random
• segregation - separating of two homologous chromosomes (along the same lines as disjunction)

• nuclear membrane forms around each new nucleus
• each chromosome still has two sister chromatids joined at the centromere but are now haploid containing only half the number of chromosomes as the original gametocyte
• cytokinesis results in the division into two haploid daughter cells
• interkinesis - short rest period that may occur between meiosis I and meiosis II in which chromosomes partially uncoil

• Mendel's second law (law of independent assortment)
  
  • states that the inheritance of one allele has no effect on the likelihood of inheriting certain alleles for other genes (not necessarily true as gene linkage still occurs)
  • genetic recombination through crossing over during prophase I minimizes inheritance of a set of alleles from a single parent as genetic information is exchanged as the chiasmata
• Mendel's first law (law of segregation)
  • states that allele pairs separate or segregate during gamete formation, and randomly unite at fertilization
  • evident from anaphase I as the two homologous chromosomes segregate through the process of disjunction

• essentially the same as prophase of mitosis
  • nuclear envelope dissolves
  • nucleoli disappear
  • centrioles migrate to opposite poles
  • spindle apparatus begins to form

• chromosomes are lined up along the equatorial (metaphase) plate through interactions of kinetochore and spindle fibers

• chromosomes are split at the centromere resulting separation of chromatids

• nuclear membrane forms around each new nucleus
• cytokinesis results in full cell division
• up to four haploid daughter cells produced per gametocyte
• oogenesis can result in under 4 haploids

• biological sex determined by X and Y chromosomes
  • XX - female; XY - male
• X chromosome carries a lot of genetic information and mutations can result in sex-linked disorders
  • more frequent in males due to only having one X chromosome - hemizygous 
  • less frequent in females as they can be heterozygous for sex-linked diseases as they have two copies of X chromosome
  • carrier - many sex-linked diseases are recessive and asymptomatic in females who have heterozygous genotypes, but can pass them on to the next generation
  • example: color-blindness 

• Y chromosome carries very little genetic information, but the SRY or sex-determining region Y is very important
  • codes for transcription factor that initiates testis differentiation leading to male gonad formation

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• highly coiled component of testes where sperm is produced
• nourished by Sertoli cells
• sperm enters the epididymis from this point

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• external pouch that contains the testes
• serves to maintain temperature slightly lower than body temperature ideal for producing sperm
• helped by a layer of muscle that can lift and lower testes for temperature adjustment

• component of testes responsible for release of androgens or male sex hormones like testosterone

• storage center of sperm after formation in the seminiferous tubules
• where flagella gain motility
• sperm stored here until ejaculation when it moves on to the vas deferens or ductus deferens

• sperm pass from the epididymis through the vas deferens during ejaculation where they head toward the ejaculatory duct
• the ejaculatory ducts from both testes fuse into the urethra where sperm passes out through the penis

• the combination of sperm and other fluids that leave the penis and enter the female reproductive tract
• other substances than sperm allow the sperm to pass easily and survive in the female reproductive system until fertilization
  • fructose - created by the seminal vesicles to nourish sperm
  • mildly alkaline properties - imparted by the seminal vesicles and prostate gland
  • clear, viscous lubricant - created by bulbourethral (Cowper's) gland to clean out urine from and lubricate the urethra during sexual arousal

• process of sperm production in the seminiferous tubules
• Process
  • spermatogonia (diploid stem cells) replicate genetic material (S stage) to become primary spermatocytes
  • spermatocytes undergo meiosis I to become secondary spermatocytes (2 for every primary)
  • secondary spermatocytes undergo meiosis II to become haploid spermatids
  • spermatids undergo maturation to become spermatozoa
  • 4 sperm cells made from one spermatogonium

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• females have separate excretory and reproductive tracts unlike males

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• female gonads
• produce estrogen and progesterone
• consist of thousands of follicles which are multilayered sacs that contain, nourish, and protect immature eggs
• eggs ovulated from uterus to peritoneal sac lining abdominal cavity and then transferred to fallopian tube or oviduct

• accepts egg from peritoneal sac
• propels egg forward with cilia lining the tubes
• connected to uterus which is the site of fetal development

• all external portions of female reproductive anatomy

• process of ova (female gamete) formation
• unlike males, females have finite supply of stem cells available for oogenesis
  • all oogonia (spermatogonia equivalent) have already undergone DNA replication to become primary oocytes by the time of birth
• Process
  • stem cells referred to as oogonia undergo DNA replication to become primary oocytes at birth
  • these primary oocytes are actually arrested in prophase I and held there until menstruation
  • upon reaching menarche (first menstrual cycle), one primary oocyte completes meiosis I to become a secondary oocyte and a polar body
  • secondary oocyte is held in metaphase II unless fertilization occurs at which point it finishes meiosis II

• created through oogenesis when making secondary oocytes from primary oocytes
• unequal division of cytoplasm during cytokinesis yields one larger secondary oocyte with ample cytoplasm and one with nearly no cytoplasm which is the polar body
• polar body doesn't produce functional gametes

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• surrounded by two layers
  • zona pellucida - first layer that is not made of cells but of protective glycoproteins capable of binding sperm
  • corona radiata - outer cell layer that adheres to oocyte during ovulation
  • fertilization occurs when pronuclei of sperm break through both layers with the help of acrosomal enzymes to create a diploid zygote

• Prior to puberty, hypothalamus restricts production of gonadotropin-releasing hormone(GnRH) 
• Puberty initiates the release of GnRH in pulses by the hypothalamus which triggers the anterior pituitary to release follicle-stimulating hormone(FSH) and luteinizing hormone(LH)
  • FSH stimulates Sertoli cells that nourish the seminiferous tubule responsible for sperm production
  • LH stimulates interstitial cells to produce testosterone which develops and maintains the male reproductive system as well as leading to secondary sexual characteristics
    • testosterone has a negative feedback effect on the hypothalamus and anterior pituitary

• Prior to puberty, hypothalamus restricts production of gonadotropin-releasing hormone(GnRH) 
• Puberty initiates the release of GnRH in pulses by the hypothalamus which triggers the anterior pituitary to release follicle-stimulating hormone(FSH) and luteinizing hormone(LH)
  • FSH leads to the production of estrogen which helps with the maintenance and development of the female reproductive system and female secondary sexual characteristics
    
    • stimulate production of the reproductive tract
    • thickening of the lining of the uterus (endometrium) during ovulation
  • LH leads to progesterone secretion from the corpus luteum which leads to development and maintenance of the endometrium

• estrogen and progesterone levels rise and fall in a cyclic pattern leading to key physiological changes in the female reproductive system known as the menstrual cycle
• breaks into four events based on rising and falling hormone levels
  • follicular phase
  • ovulation
  • luteal phase
  • menstruation
• Pregnancy and menstruation cause dramatic changes to this cycle

 [image]

• menstrual flow - starts off this phase and sheds the uterine lining of the previous cycle
• GnRH(gonadotropin-releasing hormone) levels increase in response to decreased estrogen and progesterone concentrations
  • leads to higher levels of FSH and LH
    • allow for development of several ovarian follicles which begin to produce more estrogen
    • results in the level off of GnRH, FSH, and LH concentrations
    • regrowth of endometrial lining through stimulation of vascularization and glandularization of the decidua

• process by which the ovum is released from the ovary into the peritoneal cavity
• caused by increasingly rising levels of estrogen during the late follicular phase leading to a positive feedback (normally negative) on GnRH, LH, and FSH
  • LH surge results in ovulation

• high LH levels during and after ovulation result in the formation of the corpus luteum from the ruptured follicle and the release of progesterone while estrogen levels remain high
  • progesterone maintains the uterine lining regenerated by estrogen
  • progesterone also exerts a negative feedback on GnRH, FSH, and LH levels preventing ovulation of multiple eggs

• in event that fertilization does not occur, falling LH stimulation on the corpus luteum leads to declining progesterone levels and shedding of the uterine lining so the next cycle can begin
  • in addition, GnRH lose negative feedback and are able to rise to begin the next cycle

• fertilization occurs and zygote develops into blastocyst that implants into the uterine lining and secretes hCG(human chorionic gonadotropin)
  • acts as analog of LH leading to maintenance of the corpus luteum and continued release of estrogen and progesterone
    • prevents shedding of uterine lining and secretion of GnRH
    • why missing period is sign of pregnancy
  • when fetus reaches sufficient development at 2nd trimester, it releases its own estrogen and progesterone and ceases to release hCG

• ovaries become less sensitive to FSH and LH hormones leading to ovarian atrophy
  • estrogen and progesterone levels fall
    • endometrium atrophies
    • menstruation stops
  • FSH and LH hormone levels rise due to loss of negative feedback from estrogen and progesterone
    • physical and physiological changes follow including hot flashes, flushing, bloating, headaches, and irritability 

• signaling molecules that are secreted from glands directly into the bloodstream to travel to distant target tissue(s)
• alter gene expression or cellular function at target tissue(s) by binding to a receptor
• classified into 3 groups by chemical structure
  • peptide hormones (like insulin or glucagon)
  • steroid hormones (like estrogen)
  • amino-acid derivative hormones (like catecholamines)
• classified into two groups based on target tissue
  • direct hormones 
  • tropic hormones

• amino-acids that are bound into proteins ranging from very small(ADH) to relatively large(insulin)
• derived from larger precursor polypeptides that are cleaved during posttranslational modification and transported to the Golgi apparatus where they are further modified to activate and exocytosed from the cell
• travel freely through the bloodstream due to polar nature
• receptors are all extracellular as they cannot pass through the cell membrane due to being charged
• upon binding, they trigger the release of second messengers that begin a signal cascade within the cell
• common second messengers include cAMP, inositol triphosphate (IP3), and calcium
• GPCR's are a common example of extracellular receptors that, when bound, activate or inhibit adenylate cyclase which creates cAMP resulting in a cascade of intracellular responses including protein kinase A activation
• more rapid, but shorter lasting response - hormone has to be present through the duration of the response
• names end in -in or -ine

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• derived from cholesterol and produced primarily by the gonads and adrenal cortex
• mostly nonpolar and easily able to cross the cell membrane, so most of its receptors are intracellular or intranuclear
• upon binding of steroid, conformational change (such as dimerization) allows receptor to bind directly to DNA and alter gene transcription
• have longer, less rapid responses
• because of nonpolar nature, must be carried through the blood by a carrier protein
  • some are specific and only carry one hormone like sex hormone-binding globulin
  • some are nonspecific and bind many hormones like albumin
  • increasing amounts of carrier protein can result in a perceived reduction of hormone due to binding of free hormone by carrier protein
• names end in -one, -ol, or -oid

• less common class of hormones
• made from one or two amino acids with minor modifications
• include epinephrine, norepinephrine, triiodothyronine, and thyroxine
• Catecholamines - derived from tyrosine and include epinephrine and norepinephrine; bind to G protein-coupled receptors
• Thyroid hormones - made from tyrosine with addition of several iodine atoms; bind intracellularly
• names typically end in -in or -ine

• secreted and act directly on a target tissue
• insulin is secreted from the pancreas and acts directly on the muscles to increase glucose uptake

• require an intermediary for action
• GnRH is a great example
  • GnRH from the hypothalamus stimulates LH and FSH release from the anterior pituitary
  • LH acts on gonads to stimulate testosterone production in male and estrogen in female
    
    • changes in secondary sex characteristics are brought on by this release - both GnRH and LH act as tropic hormones
• these hormones usually originate in the brain and anterior pituitary gland

• acts as a bridge between the nervous and endocrine system by releasing tropic hormones onto or neuronal signaling with the pituitary gland
  • results in organism-wide effects
  • important hypothalamic hormones
    • GnRH : FSH and LH
    • Growth-releasing hormone(GHRH): growth hormone(GH)
    • Thyroid-releasing hormone(TRH): thyroid-stimulating hormone(TSH)
    • Corticotropin-releasing factor(CRF): adrenocorticotropic hormone(ACTH)
    • prolactin-inhibiting factor(PIF):decrease in prolactin secretion
• binding of these tropic hormones causes pituitary gland to release its own hormones which can then signal other endocrine organs
  • this creates a three-organ system of communication with many points of control known as axes
    • HPA axis: hypothalamic-pituitary-adrenal cortex
    • HPO axis: hypothalamic-pituitary-ovarian
•  hypothalamic hormone release regulated by negative feedback from tropic hormones it releases or other hormones further down the pathway

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• responds to tropic hormones released by the hypothalamus into the hypophyseal portal system 
  • extremely direct connection from hypothalamus to adenohypophysis resulting in little hypothalamic hormones being found in bloodstream 
• secretes both tropic and direct hormones in response to hypothalamic hormone release (FLAT PEG mnemonic)
  • tropic hormones
    • FSH and LH in response to GnRH
      1. act on gonads
    • ACTH in response to CRF
      1. acts on adrenal cortex
    • TSH in response to TRH
      1. acts on thyroid
  • direct hormones
    • prolactin in response to decreased secretion of inhibitory PIF (dopamine) 
      1. acts on mammary glands to stimulate milk production
    • endorphins
      1. decrease perception of pain
    • growth hormone in response to GHRH
      1. promotes the growth of bone and muscle by preventing glucose uptake in tissues that are not growing and stimulating fatty acid breakdown
      2. excess associated with gigantism while deficits are associated with dwarfism

[image]

• receives direct contact from hypothalamic axons instead of tropic hormones in hypophyseal portal system
• hormones are made in the hypothalamus but stored and released from the posterior pituitary
• releases two direct hormones
  • antidiuretic hormone (vasopressin)\
    • secreted in response to low blood volume sensed by baroreceptors or increased blood osmolality by osmoreceptors
    • causes increased permeability to water in nephron collecting duct leading to increased reabsorption of water (higher blood volume, lower blood osmolality)
  • oxytocin
    • secreted during childbirth to allow for coordinated contraction of uterine smooth muscle
    • likely secreted by suckling
    • also involved in bonding behavior 
    • uniquely works on a positive feedback loop - oxytocin begets more oxytocin

[image]

• under the control of TSH release by the anterior pituitary
• functions to control metabolic rate through release of triiodothyronine (T₃) and thyroxine (T₄)
  • made by follicular cells of thyroid by iodination of tyrosine (number following T indicates # of iodine atoms)
  • increased amounts lead to increased levels of cellular respiration
  • take part in negative feedback loop that inhibits release of TSH and TRH
  • hypothyroidism - lethargy, decreased body temp, slowed respiratory and heart rate, cold intolerance, weight gain
  • hyperthyroidism - opposite of hypothyroidism
• functions to maintain calcium homeostasis through release of calcitonin
  • made by parafollicular cells or C-cells in response to high levels of blood calcium
  • increase calcium excretion from kidneys, decrease absorption through the gut, increased of storage in bone 

[image]

• set of small glands on posterior surface of thyroid
• release parathyroid hormone (PTH)
  • antagonistic hormone to calcitonin
  • raises blood calcium levels by decreasing excretion of calcium by kidneys, increasing absorption of calcium in the gut, and increasing bone resorption
  • also has minor effects on phosphorus homeostasis
  • activates vitamin D which is required for calcium and phosphate absorption in the gut

• adrenal glands located directly above kidneys and have two sections - cortex and medulla
  • cortex is outer layer
• secrete corticosteroids
  • glucocorticoids
    • include cortisol and cortisone
    • regulate glucose levels and affect protein metabolism
    • raise blood glucose by increasing gluconeogenesis and decreasing protein synthesis
    • decrease inflammation and immunologic responses (stress-induced immunosuppression)
    • cortisol is typically considered stress hormone as it is released during times of stress
  • mineralocorticoids
    •  maintain salt and water homeostasis primarily through actions on kidneys
    • most notable hormone in this class is aldosterone
      1. under control of renin-angiotensin-aldosterone system
      2. decreased blood pressure causes juxtaglomerular cells to secrete renin which cleaves angiotensinogen into angiotensin I which is then converted to angiotensin II by angiotensin-converting enzyme (ACE) causing adrenal cortex to release aldosterone
  • cortical sex hormones
    • androgens 
      1. have lesser effect on males as they make significant amounts of testosterone in testes
      2. females can develop phenotypic traits of a male fetus due to androgen disorders leading to intersex children
    • estrogens
      1. more likely to affect males

• adrenal glands have two main sections - adrenal cortex and medulla
  • medulla is inner section of the adrenal gland
• acts as a kind of extension of the nervous system through production and release of sympathetic hormones epinephrine and norepinephrine
• epinephrine
  • increase breakdown of glycogen to glucose and increase basal metabolic rate
  • increase heart rate, dilate bronchi, and alter blood flow to supply systems used in sympathetic response
• norepinephrine
  • increase heart rate, dilate bronchi, and alter blood flow to supply systems used in sympathetic response
• cortisol thought of as important for long-term stress response while catecholamines thought of as important for short-term stress response

• organ considered to have both endocrine and exocrine functions
• exocrine
  • creates digestive enzymes that are directly secreted into digestive system
• endocrine
  • produces hormones in groups of cells known as islets of langerhans
  • 3 distinct cell types found in islets of langerhans
    • α-cells secrete glucagon
    • β-cells secrete insulin
    • δ-cells secrete somatostatin

• secreted from α-cells in islets of langerhans of pancreas
• released in times of fasting (low blood glucose) to stimulate degradation of protein and fat, glycogenolysis, and gluconeogenesis

• secreted from β-cells in islets of langerhans of pancreas
• released when blood glucose levels are high
• causes uptake of glucose and storage of glycogen in skeletal muscle and liver cells as well as anabolic processes of protein and fat synthesis (not just liver and muscle)
• excess insulin causes hypoglycemia while underproduction or insensitivity to insulin can result in diabetes mellitus 
  • characterized by hyperglycemia, polyuria, and polydipsia due to excess excretion of water through urine to combat excess glucose levels
  • categorized as Type I (autoimmune attack of β-cells) and Type II (receptor-level insulin resistance)
  • Type I treated with regular insulin injections while Type II only require insulin injections when their bodies can no longer control glucose levels

• secreted by δ-cells in the islets of langerhans of the pancreas
• responds to high blood glucose and amino acid levels
• inhibits insulin and glucagon secretion
• also secreted by hypothalamus to decrease growth hormone secretion

• testes secrete testosterone
  • response to gonadotropin secretion
  • result in sexual differentiation of male during gestation and development of secondary sex characteristics
• ovaries secrete estrogen and progesterone
  • response to gonadotropin secretion
  • estrogen results in development of female reproductive system, development of secondary sex characteristics, and partially controls the menstrual cycle and pregnancy
  • progesterone also governs the menstrual cycle and pregnancy

• structure located deep within brain tissue
• releases melatonin
  • partially responsible for circadian rhythms and feelings of tiredness
  • receives projections directly from retina implying that it is partially reliant on light intensity

• terms to know:
  • nares and vibrissae
  • pharynx
  • larynx
  • glottis and epiglottis
  • trachea
  • bronchi
  • bronchioles
  • alveoli (type I and II)
  • surfactant
  • capillaries
  • pleura
  • diaphragm
  • intrapleural space
  • external intercostal muscles
  • internal intercostal muscles

[image]

• air enters through external nares of nose and is filtered through the nasal cavity by mucous membranes and vibrissae (nasal hairs)
• air then passes through the larynx and pharynx 
  • pharynx acts as pathway for food and air
  • larynx acts as pathway for only air 
    • covered by the epiglottis when not breathing (to prevent passage of food)
    • contains two vocal cords controlled by skeletal muscle and cartilage
• air moves out larynx into the trachea, followed by two bronchi which divide into many smaller bronchioles and end in alveoli
  • alveoli coated in surfactant
    • detergent that lowers surface tension to prevent total alveolar collapse
    • secreted by type II alveoli
  • alveoli are sight of gas exchange
    • branching in small size allow for maximization of surface area and efficiency of gas exchange

• parts involved
  • pleurae - membranes that surround each lung forming a closed sac against which each lung expands
  • diaphragm - thin skeletal muscle that divides thoracic and abdominal cavities; under somatic control
  • intrapleural space - space within pleural sac which contains thin layer of fluid which helps to lubricate the pleural surfaces
  • external intercostal muscles - layer of muscle between ribs 
• process
  • diaphragm flattens and the chest wall expand outward resulting in increase in intrathoracic volume
  • intrapleural space closely borders chest wall and grows in volume leading to decreasing pressure
  • negative-pressure breathing - low pressure of intrapleural space results in expansion of lungs leading to decrease pressure of lungs as well and flow of air from atmosphere into the lungs
    
    • ultimately driven by lower pressure of intrapleural space

• passive (does not require ATP) process in contrast to inhalation, but it can be active if necessary
• Process
  • relaxation of external intercostals and diaphragm result in decreasing intrathoracic volume
  • increasing chest volume leads to rising pressure of intrapleural space
  • as intrapleural space pressure becomes higher than pressure in lungs, air is pushed out resulting in exhalation
  • elastic properties of the lungs allow the lungs to passively return to their unfilled state and push air into the outside environment
  • presence of surfactant prevents total collapse of alveoli during exhalation by reducing surface tension 
• Active exhalation
  • process can be sped up during periods of activity as the internal intercostal and abdominal muscles pull the rib cage down

• total lung capacity(TLC) - maximum volume of air in lungs when one inhales completely
• residual volume(RV) - minimum volume of air in lungs when one exhales completely
• vital capacity(VC) - difference between minimum and maximum volume of air
  • TLC - RV
• tidal volume(TV) - volume of air inhaled or exhaled in normal breath
• expiratory reserve volume(ERV) - volume of additional air that can be forcibly exhaled after normal exhalation
• inspiratory reserve volume(IRV) - volume of additional air that can be forcibly inhaled after normal inhalation

[image]

• primarily controlled by collection of neurons in medulla oblongata referred to as the ventilation center 
  • fire rhythmically to cause regular contraction of respiratory muscles
  • respond to activation of chemoreceptors that are primarily sensitive to carbon dioxide concentrations and less so to oxygen concentrations
    • important as carbon dioxide acts as a way of controlling blood pH through bicarbonate buffer system
    • response to oxygen concentration has significance only during times of extreme hypoxemia
  • As partial pressure of carbon dioxide rises (hypercarbia or hypercapnia), ventilation center chemoreceptors are activated and cause an increase in respiratory rate
• Cerebrum also has control over respiratory rate (not automatic process of breathing)
  • we can choose to breath at certain rates
  • cerebrum is quickly overridden by medulla oblongata during extended periods of hypoventilation

• alveoli are one cell thick allowing efficient diffusion of carbon dioxide from the blood to the lungs and oxygen from the lungs to the blood
• alveoli receive deoxygenated blood through network of capillaries stemming from pulmonary arteries and send oxygenated blood through the capillary beds and then pulmonary veins
• Process
  • blood from pulmonary arteries arrives at alveoli w/ low oxygen and high carbon dioxide partial pressures leading to passive diffusion of carbon dioxide into the alveoli
  • at the same time, oxygen diffuses down its concentration gradient into the blood

[image]

• more rapid breathing to avoid hypoxia due to less oxygen in atmosphere
• binding dynamics of hemoglobin to oxygen altered to facilitate unloading of oxygen at the tissues
  • this is opposite of natural response of hemoglobin as decreased carbon dioxide concentration would decrease unloading of oxygen
  • phenomenon counteracted by other mechanisms
• make more red blood cells to carry oxygen
• develop more blood vessels (vascularization)

• body heat primarily regulated through vasodilation and vasoconstriction
  • vasodilation - capillaries expand allowing passage of more blood through vessels and increased dissipation of heat
  • vasoconstriction - capillaries contract restricting passage of blood and conservation of heat
• respiratory system contributes through vasodilation/constriction of nasal and tracheal capillary beds
• respiratory system also contributes through evaporation of water in mucous secretions such as the act of panting

• vibrissae w/in nasal cavity trap particulate matter and lysozyme (also in tears and saliva) in nasal cavity attacks peptidoglycan of gram positive bacteria
• mucociliary escalator - internal airways use mucus secretions to trap particulate matter and cilia propel mucus up respiratory tract to oral cavity to expelled or swallowed
• lungs (especially alveoli) contain macrophages and mast cells

• plays a role in pH balance through bicarbonate buffer system

[image]

• in event of acidemia
  • low pH sensed by chemoreceptors just outside blood-brain barrier which signal the brain to increase respiratory rate
  • increasing H⁺ concentration results in shift in bicarbonate buffer system towards formation of carbon dioxide which is sensed by respiratory center chemoreceptors leading to increased respiratory rate
  • increased respiratory rate results in increased expiration of carbon dioxide pushing the buffer system continually to the left until pH drops back to normal
• in event of alkalemia
  • high blood pH sensed by chemoreceptors resulting in slower respiratory rate which allows more carbon dioxide to enter the blood
    • pushes bicarbonate buffer system back to right resulting in formation of more H⁺ ions

• 4 chambers of heart
  • composed of two pumps:
    • right atrium and ventricle
    • left atrium and ventricle
• pulmonary circulation
• systemic circulation
• vena cavae (plural)
• different types of blood vessels

[image]

• deoxygenated venous blood of systemic circulation returns to the heart via the superior and inferior vena cavae
• blood enters the right atrium and moves to the right ventricle through the tricuspid valve
• right ventricle contracts resulting in opening of pulmonary valve and movement of blood into the pulmonary arteries
• blood travels through pulmonary arteries followed by arterioles after which point it flows into capillaries where the blood can be oxygenated by the lungs
• blood leaves alveolar capillary networks through venules and travels back towards heart through pulmonary veins until it reaches the left atrium
• left atrium feeds into left ventricle and systemic circulation

• oxygenated blood coming from pulmonary veins enters the left atrium and travels through the bicuspid/mitral valve to the left ventricle
• ventricular systole results in pumping of the blood through the aortic valve to the aorta
• blood from the aorta travels through various major arteries of the systemic circulation to structures above (superior) and below (inferior) the heart
• blood flows from major arteries to smaller arteries and then arterioles after which point it enters capillaries where gas exchange can occur
• deoxygenated blood of capillary beds then flows through venules and veins towards the heart
• veins of superior systemic circulation feed into superior vena cava while those of inferior systemic circulation feed into inferior vena cava
• both IVC and SVC feed back into the right atrium where they can enter pulmonary circulation

• Relevant structures
  • SA node
    • sinoatrial node
    • generates automatic 60-100 signals per minute, but this can be slowed down or sped up through autonomic signaling of the SNS or the vagus nerve in the PNS
    • located on wall of right atrium
  • AV node
    • atrioventricular node
    • generates automatic 40-55 signals per minute, but its real rate is dictated by SA node
    • located junction between atria and ventricles
  • bundle of His
    • consists of two long stretches of neurons and their branches
    • located along the interventricular septum (wall separating ventricles)
  • Purkinje fibers
  • intercalated discs
• Process
  • impulse initiation occurs at SA node which generates automatic 60-100 signals per minute (depending on individual)
  • atrial systole 
    • wave of depolarization spreads from SA node through myocardial cells resulting in simultaneous contraction of both atria
    • atrial kick - increase in atrial pressure forces more blood into ventricles resulting in increased ventricular pressure
  • signal reaches the AV node where it is delayed to allow complete ventricular filling
  • signal travels to bundle of His and its branches which distribute electrical signal through ventricular muscle
  • cardiomyocytes (heart's muscle cells) transmit the signal from cell-to-cell through intercalated discs resulting in coordinated contraction

[image] 

• broken into two main phases
  • systole
    • main contraction event
    • ventricular contraction and closure of AV valves leading to pumping of blood from ventricles
  • diastole
    • mainly a relaxation event
    • heart in relaxed state w/ closed semilunar valves and blood from atria fills ventricles

[image][image]

• all lined with special cell type known as endothelial cells
  • maintain vessel by releasing chemicals important in vasodilation and vasoconstriction
  • allow white blood cells to pass through blood vessel walls
  • release certain chemicals when damaged necessary for formation of blood clots
  • allow endocrine signals to pass through
• the same cell types comprise the different vessels and arteries have much more smooth muscle than veins
• 5 main types
  • arteries
    • carry blood away from heart
    • usually oxygenated blood with exception of pulmonary and umbilical arteries
    • aorta is largest artery that contributes to all other arteries in systemic circulation
    • major arteries divide bloodflow from aorta to different peripheral tissues
      • coronary, common carotid, subclavian, renal
    • provide tremendous resistance through highly muscular and elastic structures allowing maintenance of high pressure to force blood forward
  • arterioles
    • smaller, more muscular arteries 
  • capillaries
    • vessels with single endothelial cell layer
    • so small that red blood cells must pass in single-file (why sickle-cell disease causes problems - oblong RBC shape)
    • thin structure allows for easy diffusion of gases, nutrients, waste, and hormones
    • most delicate vasculature type
      • when damaged, blood can leave and enter interstitial space and result in bruising in closed spaces
  • venules
    • smaller venous structures that connect capillaries to larger veins
  • veins
    
    • carry blood toward the heart
    • carry deoxygenated blood with the exception of pulmonary and umbilical veins
    • thin-walled, less muscular vessels that are less elastic and provide less recoil than arteries
    • contain more blood of body than arterial circulation due to ability to stretch, but cardiac output is same on either side of heart
    • has to work against gravity (for most part) making them rely on valves to prevent backflow and pumps in the form of skeletal muscles to force blood against the force of gravity

• valves of heart that separate atria from ventricles
• with the semilunar valves, allow pump to create pressure w/in ventricles necessary to propel blood forward and prevent backflow
• two valves
  • tricuspid valve separates right atrium from right ventricle
    • 3 leaflets - tri-
    • leads to pulmonary circulation
  • bicuspid/mitral valve separates left atrium from left ventricle
    • 2 leaflets - bi-
    • leads to systemic circulation

• valves that separate the ventricles from the vasculature (i.e. arteries, veins, etc.)
• with the atrioventricular valves, allow pump to create pressure w/in ventricles necessary to propel blood forward and prevent backflow
• both valves have 3 leaflets
• two valves w/ self explanatory names
  • pulmonary valve
    • separates the right ventricle from the pulmonary artery
    • lead into pulmonary circulation
  • aortic valve
    • separates the left ventricle from the aorta
    • lead into systemic circulation

• total blood volume pumped by a ventricle in a minute
• the ventricle in question is unimportant as both the right and left pumps are connected in series and therefore will pass the same volumes of blood
• relies on
  • stroke volume (SV)
    • volume of blood pumped per heartbeat
  • heart rate (HR)
    • beats per minute value
  • cardiac output (CO) = HR x SV

• blood usually passes through one capillary bed before returning to the heart except in 3 portal systems
  • hepatic portal system
    • blood leaving capillary beds of gut passes through the hepatic portal vein before reaching capillary beds in the liver
  • hypophyseal portal system
    • blood leaving capillary beds of hypothalamus travels to capillary bed in anterior pituitary to allow for paracrine secretion of releasing hormones
  • renal portal system
    • blood leaving capillary beds of glomerulus travels through efferent arteriole before surrounding nephron in capillary network known as vasa recta

• Made up of two major components
  • plasma - 55%
    • portion of blood containing nutrients, salts, respiratory gases, hormones, and blood proteins (including clotting factors)
    • further refined into serum via removal of clotting factors
  • cellular fraction - 45%
    • portion of blood consisting of three major cell types
      • erythrocytes
      • leukocytes
      • plateletes
    • all major cell types in blood are formed from hematopoietic stem cells originating from bone marrow

Erythrocytes

or red blood cells

• contain millions of hemoglobin molecules designed for oxygen transport throughout the body
• have biconcave shape that allows them to enter small capillaries and maximizes surface area allowing for greater gas exchange
• lose nuclei, mitochondria, and other membrane-bound organelles as they mature which prevents use of oxygen in oxidative phosphorylation and prevents cell division
  • all must come directly from hematopoietic stem cells
• when measuring for red blood cell count in medicine, doctors measure by quantity of hemoglobin in blood in g/dL or hematocrit which is percentage of RBC's in blood sample
• red blood cell hematopoiesis is triggered primarily by erythropoietin - hormone secreted by kidney

Leukocytes

or White Blood Cells

• comprise a minute percentage of blood, but can be found in slightly heightened quantities in response to infections
• act as defenders against pathogens, foreign cells, cancer, and other materials not recognized as part of the body
• break down into two groups
  • granulocytes
    • named as such as they contain cytoplasmic granules of compounds that are toxic to invading microbes which can be released through exocytosis
    • commonly involved in inflammatory reactions, pus formation, allergies, and destruction of bacteria and parasites 
    • 3 main types
      1. neutrophils
      2. eosinophils
      3. basophils
  • agranulocytes
    • named as such as they do not contain granules
    • break into two main types
      • lymphocytes
        1. important to specific immune response
        2. some act as primary responders against an infection while others maintain a long-term memory bank of pathogen recognition
        3. B-cells: mature from hematopoietic stem cells in bone marrow and are responsible for antibody generation
        4. T-cells: mature from hematopoietic stem cells in thymus and kill virally infected cells and activate other immune cells
      • monocytes
        1. phagocytize foreign matter such as bacteria
        2. once they leave bloodstream and enter organ, they are renamed macrophages
        3. some organs have specifically-named macrophages
           • microglia in CNS
           • Langerhans cells in skin
           • osteoclasts in bone

Thrombocytes

or Platelets

• cell fragments or shards released from cells in bone marrow known as megakaryocytes
• assist in blood clotting and are present in high concentrations
• thrombocyte hematopoiesis is stimulated by thrombopoietin - a hormone secreted by the liver and kidney

• ABO antigens are comprised of three alleles for blood type
  • A and B alleles are codominant
  • O allele is recessive (must have two copies of the allele)
• Universal donors - type O blood cells express neither antien variant and therefore do not elicit immune response; can only receive type O blood
• Universal recipients  - type AB individuals can receive all blood types as no blood antigen is foreign to AB individuals
• RBC antigens are the only thing that matter when avoiding hemolytic blood transfusions as usually only RBC's (w/ no plasma) are given
• Despite being antibodies, body has immediate specific immune response to incorrect ABO antigens
  • likely due to E. coli of gut having similar proteins that body recognizes

[image]

• surface protein on RBC's originally identified in Rhesus(Rh) monkeys
• Rh^+/- refers to absence or presence of D allele (D allele actually comes in several forms)
  • can also be referred to w/ ABO blood type (O^+/-, A^+/-, etc.)
• D allele displays autosomal dominant pattern of inheritance so one copy of allele (Rh⁺Rh^-) is enough for protein expression
• particularly important to maternal-fetal medicine as women who are Rh^- will make antibodies against Rh factor protein upon exposure to fetal blood during childbirth
  • erythroblastosis fetalis - every fetus with D allele thereafter will be targeted by maternal immune system due to anti-Rh antibodies being able to cross the placenta
  • preventable w/ modern medicine

• measure of force per unit area exerted on wall of blood vessels
• measured with sphygmomanometer
  • measures gauge pressure (pressure above and beyond atmospheric pressure) in systemic circulation
  • expressed as ratio of systolic to diastolic pressures
• blood pressure naturally drops gradually when moving from arteries to veins w/ largest drop occurring across the arterioles
• CV system extremely similar to electric circuit in terms of pressure
  • ΔP = CO × TPR is similar to V=IR
    • CO = cardiac output; TPR = total peripheral resistance
  • movement of vasculature through blood relies on resistance similar to movement of current through wire
    • resistance of blood vessels dependent on length and cross-sectional area
      • longer blood vessel = more resistance
      • larger (by cross-sectional area) vessel = less resistance
  • w/ exception of portal systems, all systemic capillary beds run in parallel meaning that opening capillary beds decreases overall vascular resistance and increases cardiac output
• blood pressure modulation
  • baroreceptors - specialized neurons that detect changes in mechanical forces on walls of vessels and are capable of stimulating ANS
  • chemoreceptors - sense when osmolarity of blood is too high and can promote release of ADH/vasopressin (increased water reabsorption)
  • low perfusion to juxtaglomerular cells stimulates aldosterone secretion from adrenal cortex leading to reabsorption of sodium and water by extension - renin-angiotensin-aldosterone system
  • atrial natriuretic peptide (ANP) - secreted by specialized atrial cells in response to high blood pressure and acts as a weak diuretic to decrease blood volume (not especially effective in event of high-salt diet)
  • decreasing sympathetic impulses to allow relaxation of vasculature

Hemoglobin and Tissue-Blood Oxygen Exchange

• oxygen carried primarily by hemoglobin in erythrocytes in the blood as it has low solubility in blood plasma
• hemoglobin is a large protein w/ 4 subunits
  • each subunit contains one heme prosthetic group capable with an Fe²⁺ atom at its center
  • each heme group capable of binding one O₂ molecule (4 oxygens/heme)
  • cooperative binding - binding of each consecutive oxygen increases affinity of hemoglobin molecule for oxygen 
  • functionality negatively affected by low pH, high temperature, and high levels of 2,3-BPG
  • Bohr effect

• similarly exhibits low solubility in blood plasma
  • capable of being carried by heme, but heme has low affinity for carbon dioxide
• most is found dissolved in the blood as bicarbonate
  • in the presence of carbonic anhydrase in red blood cells, carbon dioxide reacts w/ water to become carbonic acid (bicarbonate buffer equation)
  • carbonic anhydrase also capable of converting heme back into carbon dioxide when it reaches lungs to be exhaled
• contributes to bohr effect

• increased carbon dioxide production can cause a right shift in the bicarbonate buffer equation resulting in reduced pH
• increased H⁺ concentration results in more protons capable of binding to hemoglobin and reducing its affinity for oxygen
• triggers for this rightward shift are often related to higher oxygen demand
  • increased rates of cellular metabolism result in increased carbon dioxide production and accumulation of lactic acid through glycolysis leading to decreased pH
  • allows more oxygen to be unloaded at the tissues

• contains gamma subunit which gives it a higher affinity for oxygen than adult hemoglobin (HbA)
• important as fetal hemoglobin needs to be able to take oxygen from adult hemoglobin in mother to nurture fetus

• hydrostatic pressure
  • force per unit area that blood exerts against the vessel walls
  • generated by contraction of heart and elasticity of the arteries
  • pushes fluid out of the bloodstream and into the interstitium through the capillary walls
• osmotic (oncotic) pressure
  • sucking pressure generated by solutes as they attempt to draw water into the bloodstream
  • mostly attributable to plasma proteins giving it alternative name of oncotic pressure
• at arteriole end of capillary bed, there is a net pressure moving fluid out of capillaries into tissue due to a high hydrostatic pressure and low oncotic pressure
• at venule end of capillary bed, there is net pressure moving fluid into capillaries from tissue due to fluid accumulation resulting in lower hydrostatic pressure
• Edema - accumulation of excess fluid in interstitium either due to imbalance of starling forces
  • can sometimes be caused by blockage of lymph nodes from infection or surgery
    • lymphatic system takes up some interstitial fluid 
    • lymphatic system returns this fluid to circulatory system by way of thoracic duct
    • blockage results in build-up of lymph until interstitial fluid is no longer taken up due to lack of osmotic force

[image]

• physiological response to vascular damage spearheaded by endothelial tissue and platelets (thrombocytes)
• clots form from coagulation factors and platelets when vasculature is damaged to prevent loss of blood and allow for reformation of endothelial tissue
• process
  • endothelium becomes damaged resulting in exposed connective tissue holding collagen and tissue factor
  • platelets come into contact with exposed collagen, release their contents, and begin to aggregate
  • coagulation factors are simultaneously activated in the liver by released tissue factor and initiate a complex cascade
  • results in activation of prothrombin to from thrombin by thromboplastin
  • thromboplastin converts fibrinogen into fibrin which forms small fibers that aggregate and cross-link into a woven structure that capture red blood cells and other platelets
• clot breakdown is primarily attributed to actions of plasmin generated from plasminogen

• structures involved
  • bone marrow
    • produce all leukocytes that participate in immune system through hematopoiesis
  • spleen
    • location of blood storage and activation of B-cells which turn into plasma cells
    • B-cells leaving bone marrow are considered mature but naive as they are not programmed to make antibodies for specific antigens
  • thymus
    • T-cells also arise from bone marrow but mature in the thymus
    • these cells coordinate the immune system and directly kill virally infected cells
  • lymph nodes
    • major lymphatic system structures where immune cells communicate and mount attacks
    • B-cells activated here as well
  • gut-associated lymphoid tissue (GALT)
    • named for close proximity to digestive system structures/organs 
    • tonsils and adenoids in head
    • peyer's patches in small intestine
    • lymphoid aggregates in appendix

[image]

Noncellular Defenses of Innate(Nonspecific) Immune System

• skin
  • acts as physical barrier
  • release of defensins (antibacterial enzymes)
  • antibacterial properties of sweat secreted from skin
• respiratory
  • passages of mucous membranes lined w/ cilia push particulate and foreign invaders up and out of body
  • other mucous membranes secrete lysozyme (in tears and saliva)
• gastrointestinal tract
  • stomach secretes acid which eliminates most pathogens
  • gut is colonized by millions of bacteria that make it difficult for other infectious pathogens to grow
• complement system
  • system of proteins in the blood that punch holes in cell walls of bacteria
  • classical pathway
    • requires binding of antibody to attract complement proteins
  • alternative pathway
    • does not require antibodies
• interferons
  • produced by cells that are virally infected
  • released from infected cells causing nearby cells to decrease viral and cellular protein production, decrease permeability, and upregulate production of MHC I and II receptors
    
    • mhc upregulation results in increase antigen presentation and better detection of infected cells by immune system

• type of agranulocyte (do not contain cytoplasmic granules)
• monocytes that reside in tissue
• macrophages become activated by entrance of bacterial invader in tissue and are able to recognize opsonized bacteria
• activated macrophages phagocytize invaders through endocytosis, digest invaders using enzymes, and present the pieces of the invader to other cells using MHC proteins
• macrophages also capable of releasing cytokines which stimulate inflammation/ recruit additional immune cells to area
• major histocompatibility complex (MHC)
  • binds pathogenic peptide(antigen) and carries it to cell surface to be recognized by cells of adaptive(specific) immune system
  • endogenous pathway
    • MHC class I polypeptides presented on all nucleated cells
    • any protein produced by cell is capable of being presented by MHC-I allowing immune system to monitor health of these cells and detect viral infection
      • can mark cells for attack by cytotoxic T-cells
    • called endogenous as it binds antigens from inside cell 
  • exogenous pathway
    • MHC class II polypeptides only present in antigen-presenting cells (macrophages, dendritic cells in skin, some B-cells, and some activated epithelial cells)
    • present antigens that have been phagocytized by cell meaning they are initially produced outside cell (exogenous)
    • can activate both innate and adaptive immune systems
• Pattern recognition receptors (PRR)
  • common type is toll-like receptor (TLR)
  • able to recognize category of invader (bacterium, virus, funus, parasite) and therefore produce proper cytokines to employ proper immune cells for attack

• some viruses can cause downregulation of MHC production and cancerous mutations can do the same
• NK cells are a special type of nonspecific lymphocyte that detects downregulation of MHC and causes apoptosis of virally infected or cancerous cells

• neutrophils
  • most populous leukocyte in blood
  • phagocytic like macrophages
  • target bacteria through chemotaxis and detection of opsonized bacteria
  • dead deposits of neutrophils are responsible for formation of pus during an infection
• eosinophils
  • involved in allergic reactions and invasive parasitic infections
  • release large amounts of histamine which causes vasodilation and increased leakiness of blood vessels allowing increased passage of immune cells
  • help begin inflammation as a useful defense against extracellular pathogens through histamine release
• basophils
  • involved in allergic responses
  • least populous leukocytes in blood
  • closely related to mast cells (talked about in respiratory system) but have larger granules and exist outside of tissue, mucosa, and epithelium
  • release large amounts of histamine in response to allergens to stimulate inflammatory response

[image]

• part of specific, adaptive immunity
• primary players are B-cells and the antibodies they produce
• B-cells are made from hematopoietic stem cells in the bone marrow and mature there but are still considered naive as they are not yet presented w/ specific antigen
• primary purpose of B-cells is to produce antibodies
  • every B-cell can only produce one type of antibody, but there are many B-cells to cover wide range 
• Process
  • undergo hypermutation of antigen-binding region trying to find best match for antigen through gene rearrangement
  • clonal selection - B-cells that can bind antigen w/ high affinity survive while those that do not die allowing only the most functional B-cells to continue their lineage
  • primary response
    • antigen binds leading to activation of B-cells causing them to proliferate and differentiate into memory B-cells and plasma cells
      • memory B-cells stay in the lymph nodes awaiting reexposure to the same antigen
      • plasma cells initiate primary response by releasing antibodies into the plasma to do their job
  • secondary response is more rapid and robust and is initiated by binding of antigen to memory B-cells (basis behind reasoning of vaccinations)
• isotype switching - B-cells can change the isotype of antibody they produce when stimulated by specific cytokines 
  • important as different isotypes lend themselves to different bodily functions

• Immunoglobulins or antibodies are produced by B-cells
• 3 main functions
  • opsonization - bind to antigen and employ other leukocytes (or complement system) to phagocytize antigens
  • agglutination - can cause pathogens to clump together forming large insoluble complexes that can be phagocytized
  • neutralization - block ability of a pathogen to invade tissues
  • degranulation - when present on cell surface of mast cell, antibodies can initiate release of histamine upon antigen binding
• structure
  • Y-shaped molecules
  • contain two identical light chains and two identical heavy chains
  • peptides linked together through disulfide bonds and noncovalent interactions
  • variable region
    • consist of light chain with part of heavy chain
    • contains antigen-binding site
    • very particular 
  • constant region
    • consists of bottom portion of heavy chain only
    • remain constant across antibodies in an organism and are recognized by NK cells, macrophages, monocytes, and eosinophils
  • come in five different types that are used at different times for different types of pathogens or in different location of the body

[image]

• spearheaded by T-cells that mature in the thymus
• maturation
  • positive selection - only cells that can respond to the presentation of antigen on MHC are matured while others undergo apoptosis
  • negative selection - T-cells that are self-reactive are targeted for apoptosis
  • the thymic maturation process is facilitated by thymosin released from thymic cells
  • after leaving thymus, its is mature, but the T-cell is naive as it has not yet bound first antigen
  • clonal selection occurs similarly to B-cells in that only those T-cells that bind antigen with highest affinity proliferate
• 3 types
  • helper(CD4⁺) T-cells
    • coordinate immune response by secreting lymphokines which recruit other immune cells and increase their activity
    • respond to antigen presented on MHC-II molecules
    • most effective against bacterial, fungal, and parasitic infections
    • targeted by HIV resulting in inability to mount adequate immune response
  • cytotoxic(CD8⁺) T-cells
    • directly kill virally infected cells by injecting toxic chemicals that promote apoptosis
    • respond to antigens presented on MHC-I molecules
    • most effective against viral infections
  • suppressor/regulatory T-cells also express CD4, but are differentiated by Foxp3 protein
    • tone down immune response once infection has been adequately contained
    • self-tolerance - turn off self-reactive lymphocytes to prevent autoimmune diseases
• memory T-cells can be produced and lie in wait until the next exposure to same antigen (technically not one of three types as it is more of a progenitor cell)

1. bacteria enter tissue
2. macrophages act as first responders and phagocytize bacteria and release of inflammatory mediators as well as digest and present antigens bound to MHC-II of bacteria 
3. cytokines attract inflammatory cells including neutrophils (make pus) and more macrophages
4. mast cells are activated by inflammation and degranulate releasing their histamine leading to opening of capillaries and better passage of immune cells
5. dendritic cell leaves affected tissue and travels to nearest lymph node where it presents antigen to B-cells
6. B-cells presenting correct antibody proliferate and create plasma and memory cells
7. plasma cells release antibodies to tag bacteria for destruction
8. dendritic cells also present antigen to T-cells activating CD4⁺ T-cells
9. helper(CD4⁺) T-cells release interferon gamma to activate macrophages and increase their ability to kill bacteria as well as activate B-cells 

1. cell is infected by virus
2. virally infected cell begins to produce interferons leading to reduced permeability and reduced rate of transcription and translation (both cellular and viral proteins) in nearby cells as well as systemic symptoms
3. infected cells present foreign antigens conjugated to MHC-I molecules
4. cytotoxic(CD8⁺) T-cells recognize MHC-I/antigen complex as foreign and inject toxins into cell leading to apoptosis
5. alternatively, virus may downregulate translation of MHC-I which is noticed by NK cells that recognize MHC absence leading to apoptosis of infected cell
6. memory T-cells are generated

• self-antigens - proteins and carbohydrates present on surface of every cell that signal to the immune system that they are part of body and not foreign
• hypersensitivity reactions
  
  • failures in immune system to recognize self can result in autoimmune disorders in which the body misidentifies certain self-antigens
  • immune system can also misidentify a foreign antigen as dangerous when it is not leading to allergies
• prevention methods for autoimmune reactions start early with T-cell and B-cell maturation
  • negative selection of T-cells
  • immature B-cells responding to self-antigens are eliminated before they leave bone marrow
  • these processes are not perfect and B and T cells sometimes slip through
• treatments for hypersensitivity
  • many therapies
  • glucocorticoids (alternative versions of cortisol) have potent immunosuppressive qualities

• active immunity
  • immune system stimulated to produce antibodies against specific pathogen through exposure to whole or part of pathogen
    • natural exposure through infection
    • artificial exposure through vaccines
• passive immunity
  • transfer of antibodies to an individual
  • transient because only antibodies are passed and not B-cells that produce them
  • example is transfer across placenta

• consists of lymphatic fluid(lymph) and all the vessels and ducts that carry it
  • lymph nodes - small, bean-like structures along lymphatic vessels that contain lymphatic channel, artery, and vein
  • vessels become larger as they move toward center of body until they join to make large thoracic duct in posterior chest
• functions
  • fluid leaving bloodstream and collecting in tissue either re-enters the blood vessels at the venules or is funneled through lymphatic vessels back into the blood circulation
  • transport fats from digestive system into bloodstream through lacteals (small lymphatic vessels located at center of each villus in small intestine)
    • lymphatic fluid carrying many chylomicrons takes on milky white appearance and is known as chyle
  • lymph nodes are place for antigen-presenting cells and lymphocytes to interact and B-cells proliferate and mature in germinal centers

• intracellular digestion refers to cellular metabolism while extracellular digestion is the process of nutrient absorption which occurs outside cells within the lumen of the alimentary canal
  • alimentary canal runs mouth to anus
  • sectioned by sphincters (circular smooth muscles that act as valves)
• breaks down into chemical and mechanical processes
  • chemical - enzymatic cleavage of chemical bonds
  • mechanical physical breakdown of large food particles 

• oral cavity
• pharynx
• esophagus
• stomach
• small intestine
• large intestine
• rectum
• gallbladder, salivary glands, pancreas, and liver
• enteric nervous system

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• Food enters oral cavity and undergoes minimal digestion through mastication
  • mechanical digestion through actions of tongue, lips, and teeth
  • chemical through saliva's digestive enzymes: salivary amylase/ptyalin and lipase
• food passes as a bolus into the oropharynx followed by the laryngopharynx and then continues to the esophagus
  • entry to larynx is prevented by cartilaginous epiglottis structure
  • swallowing is initiated in the muscles of the oropharynx constituting the upper esophageal sphincter 
• smooth and skeletal muscle of esophagus continue process of peristalsis down to the stomach
  • approaching contractions cause relaxation of lower esophageal sphincter opening passage to stomach
• food entering stomach through lower esophageal sphincter is broken up and digested through mechanical movements of stomach as well as enzymatic secretions (and low pH)
  
  • some absorption occurs, but much less than small intestine
• food leaves stomach through the pyloric sphincter and enters the duodenum where continued chemical digestion occurs
  • some absorption occurs, but most is in later section of small intestine
• Majority of absorption occurs in jejunum and ileum of small intestine
• food leaves body through large intestine and rectum

• entryway of food into alimentary canal where minimal digestion begins
• mastication - mechanical breakdown of large food particles through actions of teeth, tongue, and lips
  • increases surface area to allow for more efficient enzymatic digestion and prevents large particles from blocking tract
• digestive enzymes released by three salivary glands
  • salivary amylase(ptyalin) - hydrolyzes starch into smaller sugars (maltose and dextrins)
  • lipase - hydrolysis of lipids 
• bolus formed and forced back to pharynx to begin swallowing and peristalsis by tongue

• connects mouth and posterior nasal cavity to esophagus
  • nasopharynx - behind nasal cavity
  • oropharynx - back of mouth
  • laryngopharynx - above vocal cords
• epiglottis - structure of cartilaginous tissue that prevents entry of food into larynx when swallowing
• swallowing process is initiated by skeletal muscles forming the upper esophageal sphincter and continues through esophagus as peristalsis

• muscular tube connecting pharynx to stomach
• made up of both skeletal (somatic control) and smooth (autonomic control) muscles
  • top third - all skeletal muscle
  • middle third - skeletal and smooth muscle
  • bottom third - smooth muscle
• mix of skeletal and smooth muscles indicates that swallowing and proceeding peristalsis begins as a cognisant process, but quickly transitions to an automatic reflex
• peristalsis - rhythmic muscular contractions (voluntary and involuntary) through esophagus that push food bolus from upper esophageal sphincter and oropharynx to the lower esophageal sphincter and stomach
  • overriding peristalsis can occur through exposure to chemicals, infectious agents, physical stimulation, or cognitive stimulation and result in emesis
• no digestion (aside from continuing activities of salivary enzymes) occurs in esophagus

• highly muscular organ where bulk of digestion occurs
• divided into four parts
  • fundus and body
    • contain gastric glands (respond to PNS signals from vagus nerve and secrete enzymes/compounds necessary for digestion)
  • antrum and pylorus
    • contain pyloric glands
• stomach lining thrown into folds known as rugae allowing for increase surface area to maximize efficiency
• gastric glands contain 3 cell types (fundus and body)
  • mucous cells - produce bicarbonate-rich mucus that protects muscular wall
  • chief cells
    • secrete pepsinogen which is cleaved into pepsin through interactions with high H⁺ ion concentration
    • pepsin digests proteins by cleaving bonds near aromatic amino acids (tyrosine, phenylalanine, etc.)
  • parietal cells
    • create low pH environment through release of HCl
    • also release intrinsic factor which facilitates absorption of vitamin B₁₂
• pyloric glands (antrum and pylorus)
  • G-cells
    • secrete gastrin which causes parietal cells in stomach to secrete more HCl and signal stomach to contract to mix contents
• Helicobacter pylori - a rare example of a bacterium that can survive low pH stomach environment and can cause inflammation, ulcers, and gastric cancer
• contents of stomach leave through pyloric sphincter as and acidic, semifluid mixture called chyme
• few substances are absorbed in the stomach
  • examples: alcohol and aspirin

• top portion of small intestine where chyme enters through pyloric sphincter and continued digestion and minimal absorption occur
  • bulk of absorption occurs in jejunum and ileum (later sections of small intestine)
• chyme entering duodenum interacts with cells lining the luminal surface and cause release of brush-border enzymes (do not flow through lumen)
  • break down dimers and trimers of biomolecules into absorbable monomers
    • disaccharidases
      • lactose intolerance caused by lack of lactase
    • peptidases
      • aminopeptidase remove N-terminal amino acid
      • dipeptidases cleave peptide bonds to release free amino acids
  • enteropeptidase - activates other digestive enzymes through cleavage
    • trypsinogen to trypsin (peptide bond cleavage)
    • pro-carboxypeptidase A and B
• hormones release is also triggered by chyme entering duodenum
  • secretin
    • peptide hormone that causes release of pancreatic enzymes into duodenum
    • regulates pH by inhibiting HCl secretion from parietal cells and increasing bicarbonate secretion from parietal cells
  • cholecystokinin (CCK)
    • stimulates release of both bile and pancreatic juices
    • acts on brain to promote satiety
• Bile
  • bile salts, pigments and cholesterol
  • bile salts - amphipathic detergent-like molecule built from cholesterol that emulsifies fat into micelles for digestion with pancreatic lipase
• Pancreatic juices
  • complex mixture of enzymes that can digest carbohydrates, fats, and proteins in an alkaline bicarbonate solution capable of neutralizing acidic chyme

• along with duodenum, jejunum and ileum make up the three sections of small intestine
  • duodenum important primarily for digestion
  • jejunum and ileum are important for absorption
• villi
  • small, finger-like projections lining small intestine epithelial lining
  • each villus has many microvilli along it allowing for maximization of surface area to improve efficiency of absorption
  • capillary bed for absorption of water-soluble substances at center of villus
  • lacteal (lymphatic channel) for fat transport at center of villus
• simple sugars and amino acids
  • absorbed by secondary active transport and facilitated diffusion into epithelial cells and then out of epithelial cells into capillaries
    • concentration gradient created by blood constantly carrying away carbohydrates and amino acids causes these nutrients to constantly be pulled through
  • go to liver through the hepatic portal circulation
• small fatty acids (nonpolar)
  • absorbed via passive diffusion through epithelial cells and go directly through into blood
• larger fats, glycerol, and cholesterol
  • move separately through epithelial cell membranes via passive diffusion
  • reform into triacylglycerols and esterified cholesterol w/in epithelial tissue and packaged into chylomicrons 
  • diffuse out of cell and into lymph through lacteals
  • eventually lymph channels combine into thoracic duct which feeds back into blood circulation via subclavian vein
• fat-soluble vitamins (DAKE)
  • dissolve directly into chylomicrons and enter body w/ triacylglycerols and cholesterol
• water-soluble vitamins (B complex and C)
  • absorbed w/ water, amino acids, and carbohydrates across epithelial cells and into blood plasma
• water
  • much water in digestive tract gets there through digestive secretions resulting in heavy water loss
  • water regained through reabsorption mostly in small intestine (some in large)
  • drawn transcellularly and paracellularly with gradient created by solute absorption into blood

• split into 3 sections
  • cecum
    • outpocketing that accepts fluid exiting small intestine through ileocecal valve
    • appendix attaches at this section and likely has purpose in repopulating bacterial population in GI as well as fighting some bacterial infections
  • colon
    • divided into ascending, transverse, descending, and sigmoid sections
    • absorbs water and salts (NaCl) from undigested material left by small intestine
    • water absorption that did not already occur in small intestine and is primarily to achieve proper fecal consistency (avoid constipation and diarrhea) than for homeostasis purposes
  • rectum
    • storage for feces (indigestible material, water, bacteria, some digestive secretions)
    • leaves through anus
• anus
  • opening of rectum that is held closed with two sphincters
  • internal anal sphincter is under autonomic control
  • external anal sphincter is under somatic control
• large intestine filled with bacteria that are vital to our functionality
  • bacteria in gut produce vitamin K, an essential nutrient in production of clotting factors and biotin (vitamin B₇)

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• two bean-shaped organs located behind digestive organs at level of bottom rib
• made up ∼one million functional units known as nephrons
• nephrons empty into renal pelvis → ureter → bladder → urethra
• kidney has outer cortex and inner medulla
• renal hilum - deep slit in center of kidney's medial surface through which renal artery, renal vein, and ureter run and renal pelvis spans
• contains one of the few portal systems in body (hepatic and hypophyseal)
  • renal artery branches, passes through medulla, and enters cortex as afferent arterioles
  • afferent arterioles feed into highly convoluted capillary tufts known as glomeruli
  • efferent arterioles leave glomeruli and form secondary capillary bed which surrounds loop of Henle known as vasa recta
• Bowman's capsule (renal corpuscle) surrounds glomerulus and filters the blood
  • filtrate travels from Bowman's capsule to proximal convoluted tubule → descending loop of henle → ascending loop of henle → distal convoluted tubule → collecting duct

• connected to kidney through ureters
• located in lower pelvis at level of genitalia
• surrounded by muscular lining known as detrusor muscle
  • smooth muscle controlled by PNS
• two sphincters
  • internal urethral sphincter - smooth muscle; autonomic control
    • contracted in normal state
  • external urethral sphincter - skeletal muscle; voluntary control
• micturition reflex
  • stretch receptors signal PNS to cause contraction of detrusor muscle
  • internal urethral sphincter automatically relaxes
  • after this reflex, person has voluntary control over external sphincter  
• urination facilitated by contraction of abdominal musculature which increases pressure of abdominal cavity causing compression of bladder and increased flow of urine

• entire volume of blood in human body filtered through kidneys every 40 minutes
• Process
  • blood carried by afferent arterioles passes through glomerular capillaries and into Bowman's capsule
  • blood filters into bowman's space becoming filtrate with same composition of blood without cells and proteins
  • amount that is absorbed determined by Starling Forces
    • hydrostatic pressure bowman's space < hydrostatic pressure glomerulus (blood moves into bowman's space)
    • blood osmolarity of bowman's space > blood osmolarity of glomerulus (blood moves out bowman's space)  
    • hydrostatic pressure wins as its difference is more significant
  • remaining blood in glomerulus travels into efferent arterioles and empty into vasa recta(2nd capillary bed)
  •  filtrate (not bowman's space) is isotonic to blood to prevent swelling of capsule and capillaries

[image]

• provides way of eliminating excess substances in blood as well as getting rid of compounds that are too large to pass through glomerular pores
• secrete acids, bases, salts, urea, potassium and hydrogen cations, and metabolites of medications
  • urea
    • produced in the liver from ammonia (NH₃), a byproduct of the metabolism of nitrogen-containing compounds
    • can alter pH of blood and cells as a base
• occurs in proximal and distal collecting ducts

[image]

• reuptake of secreted and filtered substances through the blood
• substances like glucose, amino acids, and vitamins regularly reabsorbed
• primary control mechanism of kidneys through intervention of hormones like ADH, aldosterone, and ANP
• occurs in all parts of nephron for various substances

[image]

• first portion of nephron following bowman's space
• sight of secretion 
  • hydrogen ions (active)
  • potassium ions (active)
  • urea (active)
• sight of reabsorption
  • Na+ (active)
  • Cl- (passive)
  • H₂O (passive)
  • amino acids, glucose, and vitamins (active)
  • although significant reabsorption of sodium occurs here, filtrate remains isotonic to interstitium due to movement of water and other solutes
  • reabsorbed compounds pass from interstitium to vasa recta to re-enter bloodstream

• descending loop of Henle
  • site of water reabsorption
    • dives deep into medulla where osmolarity is ever-increasing
    • high osmolarity pulls water out of descending limb to be reabsorbed by vasa recta
    • kidney can alter this osmolarity based on water needs
      • cortex almost always isotonic with blood
      • medulla can range from isotonic w/ blood to 4 times as concentrated
  • countercurrent multiplier system
    • flow of filtrate through loop of Henle opposite direction of flow of blood through vasa recta
    • causes filtrate to constantly be exposed to hypertonic blood allowing maximal water reabsorption
• ascending limb of loop of Henle
  • site of salt reabsorption (impermeable to water)
    • ascending limb flows from deep, hyperosmolar medulla to higher areas w/ lower osmolarity
    • increasing amounts of salt are absorbed into interstitium as ascending loop approaches cortex
  • diluting segment
    • thicker section of loop of Henle located in transition from inner to outer medulla
    • thicker due to larger cells w/ many mitochondria allowing for active reabsorption of sodium and chloride
    • only segment of nephron capable of making urine more dilute than blood

[image]

• portion of nephron following ascending limb of loop of Henle
• responds to aldosterone to promote sodium reabsorption
  • aldosterone released at times of low blood pressure from adrenal cortex
  • sodium reabsorbed with water following causing increased water reabsorption as well
• site of secretion
  • H+, K+, and NH₃ (not urea)

[image]

• last segment of nephron before entering renal pelvis and is main site of regulation for urine concentration
• responsive to ADH and aldosterone to increase water reabsorption
  • collecting duct almost always absorbs some water, but amount is variable depending on presence of aldosterone and ADH
• point of no return as anything not reabsorbed by the end of the collecting duct is excreted

[image]

• as they control excretion, they also control what does and doesn't leave body making them a key part of maintaining proper blood pressure through water reabsorption
• aldosterone - steroid hormone released by adrenal cortex that causes increased reabsorption of sodium and water in DCT and collecting duct
  • decreased blood pressure activates stretch receptors associated w/ juxtaglomerular cells of kidney
  • juxtaglomerular cells of kidney release renin into blood
  • renin cleaves liver protein angiotensinogen into angiotensin I
  • angiotensin I metabolized by angiotensin-converting enzyme (ACE) in lungs to form angiotensin II
  • angiotensin II signals adrenal cortex to release mineralocorticoid aldosterone
  • aldosterone alters ability of DCT and collecting duct to reabsorb sodium
    • increased sodium reabsorption alters concentration gradient causing water to be pulled through
  • on another note, also causes increased excretion of hydrogen and potassium cations  
• antidiuretic hormone - peptide hormone made by hypothalamus and released by posterior pituitary that causes increased reabsorption of water in collecting duct
  • high blood osmolarity (associated w/ decreased blood volume) activates chemoreceptors in hypothalamus
  • hypothalamus causes posterior pituitary to release stored ADH (produced in hypothalamus)
  • ADH travels through blood to kidneys
  • ADH interacts with cells lining collecting duct causing them to be more permeable to water
  • increased water reabsorption raises blood pressure/ lowers blood osmolarity 
• effect of cardiovascular system
  • cardiovascular system attempts to control blood pressure by selectively constricting blood vessels
  • constriction of afferent arterioles results in lower blood pressure reaching glomeruli
  • stretch receptors associated with juxtaglomerular cells (next to glomerulus) are activated and activate renin-angiotensin-aldosterone system through renin release

• in line with blood pressure, kidneys also regulate osmolarity of blood - key to maintaining proper oncotic pressure (osmotic pressure created by proteins)
• kidneys control water excretion and reabsorption as well as secretion of dissolved particles allowing them to control osmolarity

• kidneys control pH of blood through selective release of hydrogen ions and bicarbonate
  
  • if blood pH is high, kidneys excrete more bicarbonate and reabsorb more H+
  • if blood pH is low, kidneys excrete more H+ and reabsorb more bicarbonate

• outer layer of skin
• subdivided into 5 layers 
  • stratum basale
    • contains stem cells and area of keratinocyte proliferation
    • keratinocyte - cells that produce keratin
    • keratin
      • protein resistant to damage that provides protection against injury, water, and pathogens
      • makes up hair and fingernails
      • calluses are excessive depositions of keratin
    • contains melanocytes
      • produce melanin which serves to protect skin from DNA damage caused by ultraviolet radiation
      • pass melanin on to keratinocytes
  • stratum spinale
    • increased connectivity of keratinocytes
    • site of Langerhans cells
      • specialized macrophages of skin
      • present antigens to T-cells to activate immune system
  • stratum granulosum
    • keratinocytes die and lose nuclei
  • stratum lucidum
    • only present in thick, hairless skin
    • nearly transparent
  • stratum corneum
    • several dozen layers of flattened keratinocytes forming barrier that prevents invasion of pathogens and loss of salts and fluids

[image]

• layer of skin below epidermis
• multiple layers
  • papillary layer
    • made up of loose connective tissue
  • reticular layer
    • denser layer 
• contains sweat glands and blood vessels serving the skin
• hair follicles originate here
• most sensory receptors can be found here
  • merkel cells (discs)
    • present at epidermal-dermal junction
    • responsible for deep pressure and tetrue sensation
  • free nerve endings
    • respond to pain
  • meissner's corpuscles
    • respond to light touch
  • ruffini endings
    • respond to stretch
  • pacinian corpuscles
    • respond to deep pressure and vibration

• lowest layer of skin
• made up of connective tissue that connects skin to rest of body
• contains fat and fibrous tissue

• sweating - responds to heat
  • body temperature rises above set point determined by hypothalamus
  • postganglionic sympathetic neurons using acetylcholine innervate sweat glands of dermis and promote secretion of water mixed w/ certain ions
  • arterioles vasodilate brining large quantity of blood to skin to maximize heat energy available for evaporation
  • sweat on skin evaporates taking body heat with it and causing body temperature to decrease
• piloerection - responds to cold
  • arrector pili muscles contract in cold
  • hairs of skin stand up on end trapping a layer of heated air near the skin
  • arterioles that feed capillaries of skin constrict to limit quantity of blood reaching skin
• body fat - important in cold conditions
  • white fat - layer of fat just below skin in humans which insulates body
  • brown fat - present mostly in infants and its cells have inefficient electron transport chain which causes more heat to be released as fuel is burned (less ATP for each running of ETC means more fuel needed and more heat released)
• although not part of skin, shivering is good one to remember
  • skeletal muscles rapidly contract
  • requires sizeable amount of ATP, but significant portion of energy from ATP converted to thermal energy

• voluntary movement controlled by SNS
• made up of repeating units of highly structured arrangements of myosin and actin leading to striated appearance
• multinucleated - formed as individual muscle cells fuse over development
• consists of two main fibers
  • red or slow-twitch fibers - high in myoglobin(red, oxygen-carrying protein) and contain many mitochondria for oxidative phosphorylation (aerobic); sustain longer contractions
  • white or fast-twitch fibers - lower in myoglobin and therefore fatigue quickly

[image]

• involuntary movement controlled by ANS
• found in almost all internal organ systems
• contain one nucleus at center of cell
• less organized arrangements of myosin and actin lead to unstriated appearance
• capable of sustained periods of low-level contraction known as tonus
• myogenic activity - unlike skeletal, can contract w/out nervous system input in response to stretch or other stimuli

[image]

• shares characteristics w/ smooth and skeletal muscles
• involuntary control by ANS
• cells typically uninucleated but can contain 2 nuclei
• striated appearance due to structured arrangements of actin and myosin
• uniquely connected through intercalated discs which contain many gap junctions allowing free flow of smaller particles like ions
  • allows for fast, direct transmission of depolarization and contraction leading to rapid, coordinated contractions
• also exhibit myogenic activity due to actions of SA and AV nodes
  • SA → AV → bundles of His → purkinje fibers
• controlled by nervous and endocrine systems
  • vagus nerve conveys PNS signaling causing slowed HR
  • Norepinephrine through SNS neurons and epinephrine from adrenal medulla bind to adrenergic receptors to increase HR and contractile force

[image]

• basic contractile unit of skeletal muscle
• made of thick and thin filaments
  • thick filaments - bundles of myosin
  • thin filaments actin, troponin, and myosin
• structure
  • Z-line - boundaries defining sarcomere (z-z is end of alphabet and end of sarcomere)
  • M-line - down center of sarcomere (middle of myosin)
  • I-band - region containing only thin filaments (I is thin letters for thin filaments only)
  • H-zone - contains only thick filaments (H is thick letter for thick filaments only
  • A-band - contains thick filaments in entirety including overlapping sections w/ thin filaments (A is for all thick filaments)
• structural change during contraction
  
  • distance between Z-lines, distance between M-lines, H-zone, and I-band become shorter
  • A-band remains constant
• attach end-to-end to form myofibrils

• made up of sarcomeres connected end-to-end to form myofibrils
• myofibrils are surrounded by specialized ER covering known as sarcoplasmic reticulum which has high concentrations of Ca⁺⁺
• myocyte surrounded by membrane known as sarcolemma
  • capable of propagating and distributing action potentials to all sarcomeres in muscle using transverse tubules (T-tubules)
  • T-tubules are perpendicular to myofibrils
• each myocyte contains many myofibrils arranged in parallel to form a muscle fiber
• many myocytes form a muscle

[image]

• motor neurons synapse onto muscle at neuromuscular junction (NMJ or motor end plate) and release acetylcholine
• acetylcholine binds to receptors on sarcolemma initiating depolarization of myocyte(s)
• action potential is triggered in myocyte and propagates to T-tubules
• T-tubules carry action potential to various sarcoplasmic reticula causing calcium release
• calcium frees myosin-binding sites on actin thin filaments by binding to regulatory subunit of troponin leading to conformational change in tropomyosin
• freed myosin-binding sites allow myosin carrying hydrolyzed ATP to bind to actin
• once bound, P_i dissociates from myosin causing power stroke that pulls actin filament over myosin filament (shortening sarcomere)
• release of ADP returns myosin to low energy form allowing for binding of ATP
• binding of ATP causes dissociation of myosin from actin (high energy state)
• hydrolysis restarts cycle

[image]

• motor neuron and all the myocytes that it controls
• all fibers controlled by a particular motor neuron must be of the same type; red/slow-twitch or white/fast-twitch
  • fast-twitch further broken down into intermediate (aerobic and anaerobic) and classic (only anaerobic) fast-twitch fibers
• more extensive/large motor units have less control and higher contractile force (biceps)
• less extensive/smaller motor units have more specific control but less contractile force (fingers)

• Efferent neuron stops signaling contraction and acetylcholine is degraded by acetylcholinesterase in synapse
• signal is terminated at NMJ and sarcolemma repolarizes
• calcium release ceases and sarcoplasmic reticulum takes of calcium from sarcoplasm
• ATP binds to myosin heads for last time in cross-bridge cycle as troponin and tropomyosin return to original confirmations covering myosin-binding sites(think of why rigor mortis occurs)

• simple twitch
  • response of single muscle fiber to brief stimulus at or above threshold
  • consists of latent, contraction, and relaxation periods as previously discussed
• frequency summation
  • muscle fiber exposed to frequent and prolonged stimulation will not relax leading to stronger and more prolonged contractions with increased stimulation
• tetanus
  • when contractions become so frequent that muscle does not relax at all over course of event 
  • prolonged tetanus can lead to muscle fatigue and eventual damage
  • tetanus disease caused by tetanospasmin toxin preventing release of GABA from neurons inhibiting motor neurons

• muscle contraction of slow-twitch muscles for prolonged periods requires large amounts of aerobic ATP production
  • requires large amounts of oxygen to feed oxidative phosphorylation
  • supplemental reserves for energy
    • creatine phosphate is produced from ATP and creatine during rest and can be used to make ATP during times of heavy use
    • myoglobin is high-affinity, oxygen-carrying protein that acts as source of oxygen reserves during times of rest
• Fast-twitch muscle fibers rely on glycolysis and fermentation to make ATP resulting in high productions of lactic acid (lactic acid fermentation)
• As oxygen levels are continually used up, slow-twitch muscle fibers switch to aerobic processes as well and lactic acid levels increase dramatically
• oxygen debt - the difference between the amount of oxygen needed by muscles and actual amount present
  • amount of oxygen required to breakdown lactic acid to pyruvate is equal to oxygen debt

• consists of skull, vertebral column, ribcage, and hyoid bone
• provides basic central framework for body

[image]

• consists of bones of the limbs, the pectoral girdle, and pelvis
• Most are long bones which are characterized by cylindrical shafts call diaphyses that swell at either end to form metaphyses and that terminate in epiphyses

[image]

• compact bone
  • dense and strong portion that gives bone characteristic strength
  • outermost portions of bone
• spongy/cancellous bone
  • microscopic lattice structure that consists of bony points called trabeculae
  • cavities between trabeculae filled with bone marrow
  • make up internal core of bone
• bone marrow
  • red marrow - filled w/ hematopoietic stem cells
  • yellow marrow - filled w/ relatively inactive fat
• long bone
  • diaphyses - long cylindrical shaft
    • full of bone marrow
  • metaphyses - portions at either end of diaphysis that are swelled out
    • full of bone marrow
  • epiphyses - bulky terminal ends of bone
    • contains spongy core for more effective dispersion of force and pressure at joints
    • internal edge holds epiphyseal (growth) plate which is cartilaginous structure from which longitudinal growth occurs; close during puberty
  • periosteum - fibrous sheath surrounding long bone to protect and serve as site for muscle attachment
• tendons attach muscle to bone
• ligaments hold bones together at joints

[image]

• bone matrix
  • where strength of compact bone comes from
  • contains collagen, glycoproteins, other peptides, hydroxyapatite crystals(calcium, phosphate, and hydroxide ions), sodium, magnesium, and potassium
• osteons or haversian systems - structural units of bone matrix
  • concentric circles of bony matrix lamellae surrounding central microscopic channel 
    • longitudinal channels are haversian canals
    • transverse channels are volkmann's canals
    • both contain blood vessels, nerve fibers, and lymph vessels to maintain healthy bone
  • lacunae - small space between lamellar rings
    • house osteocytes - mature bone cells
    • interconnected by tiny channels called canaliculi which allow for exchange of nutrients and wastes

[image]

•  osteoblasts
  • build bone
  • essential ingredients like calcium and phosphate obtained from blood
• osteoclasts
  • polynucleated resident macrophages of bone that resorb bone
  • essential ingredients like calcium and phosphate released back into bloodstream
• remodeling occurs in response to stress and endocrine hormones
  • parathyroid hormone
    • released from parathyroid glands in response to low blood calcium
    • promote resorption of bone leading to increased calcium and phosphate concentration in blood
  • vitamin D
    • activated by parathyroid hormone and promotes resorption of bone
  • calcitonin
    • released by parafollicular cells of thyroid in response to high blood calcium
    • promotes bone formation to lower calcium blood levels

• made up of firm but elastic matrix called chondrin which is secreted by chondrocytes
• more flexible and softer than bone
• avascular and not innervated
• endochondral ossification
  • when aging from fetal to adult stages, skeletal system goes from entirely cartilage to almost entirely bone
  • most bones (especially long bones) are created by this process of hardening of cartilage
• intramembraneous ossification
  • other bones (mostly skull) form from undifferentiated embryonic connective tissue (mesenchymal tissue) which is transformed into and replaced by bone

• made up of connective tissue
• immovable joints
  
  • made up of bones that fuse together to form sutures or similar fibrous joints
  • found primarily in head where they anchor bones of skull together
• movable joints
  • permit bones to shift relative to one another
  • strengthened by ligaments
  • consist of synovial capsule which encloses actual joint or articular cavity
    • contains soft synovium which secretes synovial fluid to lubricate movement of structures
    • articular cartilage coats articular surfaces of bones so impact is restricted to lubricated joint cartilage, not bones

[image]

• mendelian genetics refers to alleles as dominant and recessive in terms of expressed genotype
  • homozygous - two copies of same allele
  • heterozygous - one copy of dominant and one copy of recessive
  • hemizygous - only one allele present for given gene - sex chromosomes
• does not capture full story as different patterns of dominance exist
  • complete dominance - only one dominant and one recessive allele exist for a given gene
    • presence of one dominant allele masks recessive allele
    • standard definition described by mendel
  • codominance - more than one dominant allele
    • simultaneous expression of both alleles
    • blood type is good example
  • incomplete dominance
    • heterozygote expresses phenotype that is intermediate between the two homozygous genotypes
    • good example seen in flowers

• probability of expression
• population measure that defines the proportion of the allele-carrying population that expresses the expected phenotype
  • probability that having given genotype will lead to expression of respective phenotype
• Comes in levels
  • full penetrance
    • >40 sequence repeats causes 100 percent expression of Huntington's disease
  • high penetrance
    • <40 sequence repeats causes many to express disease but not all
  • reduced penetrance
    • fewer sequence repeats can be correlated with decreasing levels of penetrance
  • low penetrance
  • nonpenetrance
    • no correlation between genotype and phenotype

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• variability of expression
• individual measure similar to penetrance, but does not look at populations or percentages of individuals
• defined as varying phenotypes despite identical genotypes and looks more at varieties of phenotypes instead of presence or lack of phenotype (penetrance)
• come in levels
  • constant (narrow) - all individuals with given genotype express same phenotype
  • variable - individuals with same genotype have different phenotypes

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• basic tenets
  • genes exist in alternative forms known as alleles
  • an organism has two alleles for each gene, one inherited from each parent
  • the two alleles segregate during meiosis resulting in gametes that carry only one alleles for any inherited trait
  • if two alleles of organism are different, only one will be fully expressed and other will be silent
    • expressed is dominant
    • silent is recessive
• basically states that separation of alleles during meiosis causes child to inherit one allele from each parent
• the analogue in modern genetics has been found in anaphase I of meiosis where chromosomes are separated into different cells

• inheritance of one gene does not affect the inheritance of another gene (discounts modern findings of gene linkage)
• analogue in modern genetics found during prophase I of meiosis when independently replicated chromosomes of one parent combine with homologous chromosomes of other parent to form tetrads and recombination occurs
  • individual and random recombination of genes allows one gene to be inherited independently of others

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• mutations can be caused by ionizing radiation, chemical exposures to mutagens, natural mistakes made by DNA polymerase, and transposons
• point mutation - single nucleotide mutation in DNA
  • silent - change in nucleotide has no effect on final protein
    • most commonly occurs when changed nucleotide is transcribed to be third nucleotide in codon due to degeneracy or wobble in genetic code
  • missense - change in nucleotide causes substitution of one amino acid for another
  • nonsense - change in nucleotide results in substitution of one amino acid with a stop codon causing truncation
• frameshift mutations - nucleotides are inserted or deleted from genome causing shifting of the reading frame
  • typically results in major changes in amino acid sequence or premature truncation
  • include insertion and deletion

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• larger-scale mutations in which large segments of DNA are affected, not just particular genes
• types
  • deletion - large segment of DNA lost from chromosome (small-scale are frameshift)
  • duplication - segment of DNA copied multiple times in genome
  • inversion - segment of DNA is reversed w/in chromosome
  • insertion - segment of DNA moved from on chromosome to another (small-scale are frameshift)
  • translocation - segment of DNA from one chromosome swapped w/ segment of DNA from another chromosome

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• class of deleterious mutations in which genes required for metabolism are affected
  • metabolites build up in various pathways causing potentially harmful effects if intervention does not occur
• PKU (phenylketonuria)
  • mutation in phenylalanine hydroxylase enzyme required for complete metabolism of phenylalanine
  • build up of toxic metabolites cause seizures, impairment of cerebral function, and learning disabilities

• flow of genes between species
• hybrid - individuals of different but closely related species mate to produce hybrid offspring
  • usually unable to mate as they have odd numbers of chromosomes making normal homologous chromosome pairing impossible during meiosis
  • some offspring can reproduce and carry on genes from both parent species

• genetic drift - changes in composition of gene pool due to chance
  • more pronounced in smaller populations
• founder effect - extreme case of genetic drift in which small population of species finds itself in reproductive isolation from other populations
  • due to any number of bottlenecks that drastically decrease population size and therefore size of gene pool 
  • inbreeding - encouraged by smaller population size in later generations
    • encourages homozygosity
    • reduction in genetic diversity
    • can lead to increased prevalence of certain traits and diseases
    • inbreeding depression - loss of genetic variation causes reduced fitness of population
• outbreeding (outcrossing) - introduction of unrelated individuals into a breeding group resulting in increased variation w/in gene pool and increased fitness of population

• used to determine an unknown genotype
• organism with unknown genotype is crossed with organism known to be homozygous recessive

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• gene linkage
  • genes located close together on chromosome are less likely to separate during crossing over and more likely to have linked patterns of inheritance
  • genes located farther apart on chromosome are more likely to have a chiasma (point of crossing over) between them and less likely to have linked patterns of inheritance
• recombination frequency (θ) - likelihood that two alleles are separated from each other during crossing over
  • roughly proportional to distance between genes on chromosome
  • tightly linked genes have θ = 0%
  • weakly linked genes have θ's approaching 50%
• the idea of gene linkage and recombination frequency can be used to create a map of genes on a chromosome
  • one map unit/centimorgan is equivalent to a 1% chance of recombination occurring between two genes

• used to describe populations that:
  • are very large (no genetic drift)
  • do not have mutations affecting their gene pool
  • have random mating between individuals
  • do not experience migration of individuals in or out
  • have genes that are all equally successful at reproducing
• p + q = 1
  • where p is frequency of dominant alleles and q is frequency of recessive alleles
• p² + 2pq + q² = 1
  • where p² is the frequency of homozygous dominant genotypes
  • where 2pq is the frequency of heterozygous dominant genotypes
  • where q² is the frequency of homozygous recessive genotypes
  • p² + 2pq also represents frequency of dominant phenotype

• Organisms produce offspring, few of which survive to reproductive maturity.
• Chance variations w/in individuals in a population may be heritable.  If these variations impart a slight survival advantage to an organism, the variation is termed favorable.
• Individuals with a greater preponderance of favorable variations are more likely to survive to reproductive age and produce offspring resulting in an increase in these traits in future generations.  This reproductive success is termed fitness and is directly related to genetic contribution of individual to next generation.

• differential reproduction - when a mutation or recombination results in a change that is favorable to the organism's reproductive success, that change is more likely to pass on to next generation
• inclusive fitness - measure of an organism's success in population based on number of offspring, success in supporting offspring, and ability of offspring to support others
  • Darwin's theory was based solely on number of viable offspring of individual
  • current theory also takes behaviors w/in population into account such as altruism
• punctuated equilibrium - theory to explain sudden burst of new species over relatively small time periods w/in long periods of minimal change
  • suggests that changes in some species occur in rapid bursts rather than evenly over time

• stabilizing selection - keeps phenotypes w/in specific range by selecting against extremes

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• directional selection - pushing of standard phenotype toward extrema due to adaptive pressure

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• disruptive selection - two extreme phenotypes are selected for over norm
  • facilitated by polymorphisms
    • naturally occurring differences in form between members of same population
  • also facilitated by adaptive radiation
    • describes rapid rise of number of different species from common ancestor 
    • allows for various species to occupy different niches
    • favored by environmental changes or isolation of small groups of ancestral species

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• species - largest group of organisms capable of breeding to form fertile offspring
• isolation - when progeny of separate populations can no longer interbreed and caused by pre-and-postzygotic mechanisms
  • prezygotic mechanisms - prevent formation of zygote completely
    • temporal isolation
    • ecological isolation
    • behavioral isolation
    • reproductive isolation
    • gametic isolation
  • postzygotic mechanisms - allow for gamete fusion but yield either nonviable or sterile offspring
    • hybrid inviability
    • hybrid sterility
    • hybrid breakdown

• prezygotic mechanisms prevent formation of zygote completely
• include:
  • temporal isolation
    • mating at different times
  • ecological isolation
    • living in different niches w/in same territory
  • behavioral isolation
    • lack of attraction between members of the two species due to differences in pheremones, courtship displays, etc.
  • reproductive isolation
    • incompatibility of reproductive anatomy
  • gametic isolation
    • intercourse can occur, but fertilization cannot

• Postzygotic mechanisms allow for gamete fusion but yield either nonviable or sterile offspring
• Include:
  • hybrid inviability
    • formation of zygote that cannot develop to term
  • hybrid sterility
    • forming hybrid offspring that cannot reproduce
  • hybrid breakdown
    • forming first-generation hybrid offspring that are viable and fertile, but second-generation are inviable or infertile

• Divergent evolution - independent development of dissimilar characteristics in two or more lineages sharing common ancestor
  • seals and cats share some common ancestor as mammals
• parallel evolution - process whereby related species evolve in similar ways for a long period of time in response to analogous environmental selection pressures
  • In butterflies, many close similarities are found in the patterns of wing colouration, both within and among families
• convergent evolution - independent development of similar characteristics in two or more lineages not sharing a recent common ancestor
  • fish and dolphins both developed fins, but are entirely different types of vertebrates