Biology 277: Combined Lecture Notes

Chapter 16: Senses

• Sensory receptors can respond to a stimulus and initiate sensory input to the CNS
• provide information about internal and external environments to CNS. Responds to stimuli
• Specific Types: eyes-light; ear-sound
• Stimulus - change in the internal or external environment
• Sensation - conscious awareness of incoming sensory information
• has to reach the cerebral cortex, only a fraction of a stimuli can be perceived

Sensory Receptors: has to maintain RMP

Transducers: change one form of energy into another

• stimulus energy into an electrical signal (action potential)

Features that allow transduction

• Resting membrane potential
• Modality gated channels: open to a specific type of stimulus (in plasma membrane) to CNS via sensory neurons

Receptive Field

• Entire area within which the dendritic endings of a single sensory neuron are distributed*
• Small receptive field - allows for a precise location, if there is a lot sensory neuron # increases. Increases energy usage which is not productive for the body
• Large receptive field - covers more of a general region, not as precise, not a lot of energy required

Sensory Characteristics Provided by Sensory Receptors

• Modality - type of stimulus
• the brain is interpreting that information; eye (optic nerve), occipital lobe, vision
• Location - determined by which receptive field is active
• we can get information from different locations, specific sensory neurons
• Intensity - frequency of nerve signals to CNS
• change in the number of nerve signals being sent
• Duration - determined by receptor adaptation
• duration of the stimulus

Adaptation

• Tonic Receptors
• Limited adaptation
• Continuous response
• Continuously generate nerve signals
• Slowly decrease quantity of stimulus relayed overtime
• Phasic Receptors
• Detect new or change in a stimulus
• Sensitivity decreases
• Rapid adaptation

Sensory Receptor Classification

Receptor Distribution

• General sense receptors - simple in structure and located throughout the body
  • Somatic Sensory
    • Tactile receptors - located within skin and mucous membranes; detect texture, pressure, vibration, temperature,pain
    • Proprioceptors - located in joints, muscles, tendons, detect stretch and pressure, looks at relative position of the body
  • Visceral Sensory
    • Walls of internal organs - and blood vessels, detect smooth muscle stretch, chemical changes, temperature, pain
• Special sense receptors
  • Specialized, complex receptors in the head (5 special senses)

Stimulus Origin

• Exteroceptors - detect stimuli from the external environment. Somatic sensory, tactile, mucous membranes, and special senses
• Interoceptors - detect stimuli from internal environment, keeps CNS informed, visceral sensory
• Proprioceptors - detect stimuli from musculoskeletal system

Modality of Stimulus

• Chemoreceptors - chemicals dissolved in fluid
• Thermoreceptors - changes in temperature
• Photoreceptors - changes in light intensity, color, movement
• Mechanoreceptors - distortion of plasma membrane
  • Baroreceptors
  • Tactile receptors
• Nociceptors - painful stimuli - injury or damage
  • Somatic nociceptors - detect chemical, heat, or mechanical damage. Touching a hot pan.
  • Visceral nociceptors - detect only internal organ damage. Detect stretch when you’ve eaten too much, and detects trauma

Tactile Receptors - most numerous, mechanoreceptors located within skin

• Unencapsulated - dendritic endings have no protective covering
• Encapsulated - dendritic endings have a protective covering

Unencapsulated Tactile Receptors

• Free nerve endings - Terminal ends of sensory neuron dendrites; reside in the skin surface. Detect temperature, pain, some light touch and pressure
  • Terminal ends - tonic or phasic
• Root hair plexus - located in the reticular layer of dermis, detects hair displacement.
  • Wrap around hair follicles
• Tactile discs - single layer, responds to light touch. Tonic
  • Flattened endings that extend to tactile cells

Encapsulated tactile receptors - dendritic endings wrapped by connective tissue, or covered by connective tissue or neurolemmocytes

• End bulbs - dermis of skin and mucous membranes. Detects light pressure and low frequency vibrations. Tonic
  • Wrapped in connective tissue
• Lamellated corpuscles - deep in dermis, subcutaneous layer, breast, external genitalia, walls of some organs. Detects coarse touch, high frequency vibrations. Phasic
  • Wrapped with neurolemmocytes and concentric layers of connective tissue
• Bulbous corpuscles - dermis and subcutaneous layer. Detects continuous deep pressure, distortion of skin. Tonic
  • Wrapped in connective tissue
• Tactile corpuscles - dermal papilla of skin, sensitive regions. Discriminative light touch, recognition of texture and shape. Phasic
  • Enclosed by modified neurolemmocytes, covered with dense irregular connective tissue

Proprioceptors - specialized mechanoreceptors. Tonic

• Muscle spindle - detects stretch in skeletal muscle
• Golgi tendon organ - detects stretch in a tendon
• Joint kinaesthetic receptor - detect stretch in articulation capsule

Referred Pain

• Occurs when sensory nerve signals from certain viscera are perceived as originating not from the organ, but from somatic sensory receptors within the skin and skeletal muscle
• Many somatic sensory neurons and visceral sensory neurons conduct nerve signals on the same ascending tracts, this causes the somatosensory cortex in the brain to inaccurately determine the actual source of the stimulus
• Stimulus is localized incorrectly
• Myocardial Infarction: cardiac problems are referred pain because the heart’s sympathetic innervation originates from the T1-T5 segments of the spinal cord
• Pain is referred to the skin innervated by T1-T5
• Left arm pain!

January 5, 2024:

Olfaction - connected to gustation, a special sense, chemoreceptor/exteroceptor

• odorants (food, people, danger) dissolved in mucus detected by chemoreceptors
• Olfactory epithelium - receptor sensory organ
  • Olfactory receptor cells - superior region of nasal cavity
    • Olfactory hairs
      • Dendrites into mucus
      • Contain chemoreceptor
      • Detection of a specific odorant molecule which depends on the hairs
• Supporting Cells
  • Sustain olfactory receptor cells
• Basal Cells
  • Neural stem cells, replace olfactory receptor cells
  • Every 40-60 days
  • Sensitivity declines overtime
• Lamina propria - areolar connective tissue; inside olfactory epithelium
  • Blood vessels
  • Nerves
  • Olfactory glands - mucin production

Olfactory Nerve Structures and Pathway

• Olfactory nerves - bundles of axons that run through cribiform plate to olfactory bulbs
• Olfactory bulbs - terminal ends of olfactory tract, inferior to frontal bone
  • Synapse with secondary neurons (below)
  • Mitral cells
  • Tufted cells
• Olfactory Tracts - project to primary olfactory cortex (temporal lobe), hypothalamus, amygdala
  • Do not project through thalamus

Detecting Smells

• Odorants
• Odorant-binding proteins - allow odorants to bind to hairs, get stimulated
• G protein activated - stimulate adenylate cyclase
  • cAMP - 2nd messenger, opens cation channels (Na+ and K+), depolarizes
  • Start with graded potentials that turn into action potentials
• Action potential - down the axon
  • Release of NT
  • Stimulation of patterns in glomeruli

Sensory Information Reaches

• Cerebral cortex - temporal lobe, sensory perception
• Hypothalamus - controls visceral sensory reaction to smell
• Amygdala - recognition of an odor, associated with emotion
• Adaptation is rapid - prevents more nerve potentials from

Gustation - taste, tastants, gustatory cells

• Papillae of tongue - elevations of epithelia and connective tissue
  • Filiform
    • No taste buds
    • Mechanical function
    • Assists in texture, manipulation of food, etc
    • Anterior ⅔ of tongue
  • Fungiform
    • Few taste buds
    • Tip and sides of tongue
  • Foliate
    • Taste buds not well developed
    • Posterior lateral portion of tongue
  • Vallate
    • Largest but least numerous
    • Innervated on posterior surface
    • Most taste buds

Taste Bud - sensory receptor organ

• Gustatory cells
  • Chemoreceptor
  • Microvilli (receptor)
  • Extend to taste pore
• Supporting cells
  • Support
• Basal cells
  • Replace gustatory cells
  • 7-9 days
  • Sensitivity decreases
• Mechanoreceptors (texture)
• Thermoreceptors (temperature)

Gustation Pathway

• Gustatory cells - primary neuron
• Sensory neurons
  • Facial nerve (CN VII) - anterior ⅔ of tongue
  • Glossopharyngeal (CN IX) - ⅓ posterior portion of tongue
• Medulla oblongata - nucleus solitarius, synapse with secondary neuron
• Thalamus - synapse with tertiary neuron
• Gustatory Cortex (insula) - conscious perception of taste

Five Taste Sensations

• Sweet
  • Organic molecules
• Salt
  • Metal ions
• Sour
  • Acids
• Bitter
  • Alkalenes
• Umami
  • Amino acids

Vision Accessory Structures

• Extrinsic eye muscles - 6 muscles for movement
• Eyebrows - non verbal communication, protection from sweat
• Eyelashes - prevent particulates from entering. Sensory receptors at base that trigger blinking reflex
  • Sebaceous gland
  • Modified sweat gland
  • At base
• Eyelids - orbicularis oculi, thin skin
  • Tarsal plate
    • Tarsal gland - sebaceous gland
  • Palpebral fissure - eye slit (opening)
  • Medial and lateral palpebral commissures
    • Lacrimal peduncle

Accessory structures

• Conjunctiva - transparent lining
  • Does not cover cornea
  • Stratified columnar epithelium - specialized
  • Ocular conjunctiva - covers anterior portion of sclera
  • Palpebral conjunctiva - inner surface of eyelid
  • Conjunctival fornix - junction between ocular and palpebral conjunctiva
  • Goblet cells
  • Blood vessels
  • Nerve endings

January 8, 2024:

• Lacrimal apparatus - produce, collect, drain lacrimal fluid
  • Lacrimal gland - produce lacrimal fluid and drain to ducts to surface to blink
  • Lacrimal puncta - drains
  • Lacrimal canaliculus - drains
  • Lacrimal sac - drains
  • Nasolacrimal duct - drains to nasal cavity. Mixes with mucus to drain to the pharynx

Lacrimal Fluid

• Contains water and sodium ions
• Lysozyme (antibacterial enzyme)
• Reduces fraction
• Cleans and moistens
• Prevent bacteria
• Provision of oxygen and nutrients to cornea

Eye Structure

Three tunics

• Fibrous Tunic (external)
  • Sclera - dense irregular connective tissue
    • Provides - shape
    • Protects - inner components
    • Attachment site - for extrinsic eye muscles
  • Cornea
    • Transparent and convex shaped
    • Bends light rays
    • Inner layer composed of simple squamous epithelium
    • Middle layer of collagen fibers
    • Outer layer of corneal epithelium
• Vascular Tunic (middle) - house blood vessels, lymph vessels, and intrinsic eye muscles
  • Choroid - areolar connective tissue, blood vessels, melanocytes
    • Two functions
      • Melanin pigment to absorb extraneous light
      • Supply oxygen and nutrients to retina
  • Ciliary body
    • Ciliary muscle
      • Band of smooth muscle connected to lens (alters the shape)
    • Ciliary processes
      • Contains capillaries that secrete aqueous humor
  • Iris - two smooth muscle layers, melanocytes, vascular and neural structures. Divides anterior cavity into an anterior and posterior chamber. Plays a role in the opening/closing of pupils
    • Pupil
• Retina (internal)
  • Pigmented layer - provide vitamin A with photoreceptor cell and absorbs extraneous light
  • Neural layer - houses photoreceptors and aides in transduction of light energy

Cavities

• Posterior cavity - behind lens
  • Vitreous humor
    • Permanent fluid
    • Transparent, gelatinous fluid
    • Embryonic
    • Keeps retina at the back
    • Maintains eye shape
• Anterior cavity - in front of lens
• Anterior chamber
  • • Between cornea and iris
  • Posterior chamber
    • Between iris and lens
  • Aqueous humor
    • Ciliary processes
    • Scleral venous sinus
    • Circulates around eye
    • Provide oxygen and nutrients to lens and cornea
    • Transparent, watery fluid
    • From ciliary processes

Pupil

• Diameter controlled by iris
• Sphincter pupillae muscle
  • Concentric pattern that constricts
• Dilator pupillae muscle
  • Radial pattern that dilates
• One muscle can contract at a time
• Body has a pupillary reflex
• Tested to see if there is brain trauma

Retina

• Pigmented layer - vitamin A, internal to choroid
• Neural layer - absorbs light for transduction
  • Photoreceptor cells
    • Rods - function in low light. Conduct graded potentials
    • Cones - function in bright light and aides in color visions. Conduct graded potentials
    • Photo pigment molecules - react to light
  • Bipolar cells
    • dendrites synapse with photoreceptors; axons synapse with axons of ganglion cells
    • Conduct graded potentials
  • Ganglion cells
    • Axons exit the back of the eye
    • Form the optic nerve
    • Can conduct action potentials
  • Other retinal cells
    • Horizontal cells
      • Regulate and integrate signals from photoreceptor cells to bipolar cells
    • Amacrine cells
      • Involved with regulation and integrating signals from bipolar to ganglion cells
      • Capable of action potentials

Graded potentials

Action potentials

Regions of Retina

• Optic disc - no photoreceptors. “Blind spot”. Where axons exit to form the optic nerve
• Macula lutea
  • Fovea centralis - depressed pit that contains mostly cones and a few rods
• Peripheral retina - contains primarily rods and functions in dim light

Physiology of Vision

Light refraction - light bending that passes through different densities

• Cornea
• Lens
  • Suspensory ligaments - attached to the periphery of the lens. Transmit tension on lens allowing it to change shape, to allow how light is refracted
  • Ciliary muscles - aides suspensory ligaments
  • Bending of light rays
  • Transparent
  • Has layers of crystalline protein enclosed in a capsule

Focusing of light

• Objects closer than 20 feet
  • Near response
  • Convergence - eyes directed medially due to extrinsic muscles. Sends direct message to fovea centralis
  • Accommodation - ciliary muscles contracting. Decrease tension of suspensory ligaments to thicken lens shape (relaxed)
  • Sphincter pupillae muscle contracts
• Objects farther than 20 feet
  • Eyes directed forward by extrinsic muscles
  • No convergence (eyes move forward)
  • Ciliary muscle relax, suspensory ligaments tighten
  • Lens flatten (resting position)
  • Light refracted less
  • No accommodation
  • Dilator pupillae contracts to maximize visual input
  • No near response

Phototransduction

• Photoreceptor parts
  • Outer segment
    • Photopigment-containing discs - absorb light, replace every 10 days, old ones engulfed by phagocytes
  • Inner segment
    • Organelles
  • Cell body
    • Nucleus
  • Synaptic terminals
    • Synaptic vesicles - hold neurotransmitter glutamate
• Rods - longer and narrower, numerous, sensitive (work in dim light), no color recognition
  • Dim light
  • Periphery of retina
• Cones - less numerous, color recognition, precise visual sharpness
  • Bright light
  • Fovea centralis

Photopigments

• Composed of opsin (protein) and retinal (light absorbing molecule formed from vitamin A)
• Pigment types
  • Rods - rhodopsin
  • Cones - photopsin
  • Blue cones - short wavelengths
  • Green cones - intermediate wavelengths
  • Red cones - long wavelengths

Bleaching reaction and regeneration of rhodopsin

1. Rhodopsin (opsin + cis-retinal) absorbs light rays
2. Cis-retinal is transformed to trans-retinal
3. Trans-retinal dissociates from opsin, as opsin becomes activated (bleaching reaction)
4. Trans-retinal is reconverted to cis-retinal within the pigmented layer of the retina using ATP
5. Cis-retinal associates with opsin to reform rhodopsin

Dark adaptation

• Bright light to low light

Light adaptation

• Low light to bright light

Phototransduction in Rod Photoreceptors

Initiating nerve signals

• Dark - rods depolarized
  • cGMP produced
  • Dark current
  • Glutamate NT released by rods
  • Bipolar cells hyperpolarized
  • Ganglion does not send signal
• Light - rods hyperpolarized
  • Light splits rhodopsin
  • cGMP broken down
  • Dark current stops
  • Glutamate NT not released by rods
  • Bipolar cells depolarize, release glutamate NT
  • Ganglion cell excited, sends signal

Visual Pathway

• In retina
  • Photoreceptor to bipolar cells to ganglion cells
• Optic nerves
  • Converge at optic chiasm
  • Medial axons cross at opposite sides
  • Lateral axons on same side
• Optic tract
  • Extend to thalamus to geniculate nucleus to tertiary neuron to visual cortex (perception)
• Midbrain
  • Superior colliculus - coordination of reflexive eye movements (extrinsic eye muscles
  • Pretectal nucleus - pupillary reflex, accommodation reflex (lens)

Three Regions of the Ear

• External ear
  • Auricle
  • External acoustic meatus - take sound to tympanic membrane
• Middle ear
  • Tympanic cavity - air filled
  • Auditory tube - connect to nasopharynx
  • Auditory ossicles - 3 bones
• Inner ear
  • Membranous labyrinth
  • Bony labyrinth
• Auditory ossicles - amplify sound waves to oval window
  • Malleus
  • Incus
  • Stapes
• Tensor tympani muscle
• Stapedius muscle
• Restrict ossicle movement during loud sounds

Inner ear

• Bony labyrinth - maze like space in temporal bone
  • Perilymph - fluid
• Membranous labyrinth - membrane lined fluid-filled tube. Receptors for hearing and equilibrium
  • Endolymph - fluid high in K+

3 regions of bony labyrinth

• Cochlea
  • Cochlear duct
• Vestibule
  • Utricle and saccule
• Semicircular canals
  • Membranous semicircular ducts

Structures for hearing

• Cochlea - snail shaped chamber
  • Cochlear duct - scala media
    • Endolymph - fluid
    • Vestibular membrane - roof
    • Basilar membrane - bottom
  • Scala vestibuli
  • Scala tympani
  • Helicotrema - small channel that connects the scala vestibuli to scala tympani
• Spinal organ - sensory structure for hearing, thick sensory epithelium
  • Hair cells - release NT, has receptors, inner sensory receptor for hearing
  • Supporting cells - both rest on basilar membrane

Pathway from sound wave to nerve signal

1. Sound wave collected by auricle
2. Tympanic membrane vibrates
3. Ossicles vibrate (amplify sound)
4. Stapes vibrate at oval window
5. Pressure waves created within the perilymph fluid in the scala vestibuli
6. Distortion of vestibular membrane
7. Pressure waves created within the endolymph fluid in cochlear duct
8. Depending on the frequency, different areas on basilar membrane move
9. Hair cells are distorted
10. Nerve cell propagation

Cochlear hair cell stimulation

• as basilar membrane moves up hair cells go to the tectorial membrane
• stereocilia bends
• ion channels open
• potassium into the cell
• depolarization of inner hair cell
• release of neurotransmitter
• action potential along cochlear branch

Perception of sound

• Properties
  • Pitch - stiffness in basilar membrane
  • Frequency - sound as high or low, rate of back and forth motion of vibrating object
• Loudness
  • amplitude of sound waves (decibels)
  • quiet: small movement within basilar membrane
  • loud: big movements within basilar membrane; faster rate of nerve signal sent

Auditory pathway

• Hair cells through cochlear branch (nerve signal) to cochlear nucleus (medulla oblongata)
• Inferior colliculus (midbrain)
  • Reflex to loud sounds to skeletal muscles
• Superior olivary nucleus (pons)
  • Localize sound and reflexive contraction middle ear muscles
• Medial geniculate (thalamus) - filter out background noise
• Relay from thalamus to primary auditory cortex - conscious perception

Equilibrium - awareness and monitoring of head position

• Vestibular apparatus - adjust
  • Utricle - static equilibrium, linear acceleration
  • Saccule - static equilibrium, linear acceleration
  • Semicircular canals - angular acceleration (head rotation). Info sent to brain
• Macula - static equilibrium, linear acceleration (sensory receptor)
  • within utricle and saccule
  • hair cells - stereocilia - kinocilium - gelatinous mass (otolithic membrane)
  • supporting cells

Static equilibrium

• Upright head position
  • otolithic membrane applies pressure directly on hair cells - minimal stimulation

Linear acceleration

• Altered head position
  • otolith membrane bend stereocilia
  • changes number of neurotransmitter release
  • changes stimulation of sensory neuron

Base of semicircular canals

• Ampulla
  • Crista ampullaris - hair cells - supporting cells

Angular acceleration of head

• as head rotates, endolymph fluid pushes against cupola (bend stereocilia)
• voltage change
• depolarization of vestibular branch

Equilibrium pathways

Nerve signals sent on vestibular branch to

• Vestibular nuclei (medulla oblongata)
  • Reflexive eye movement
  • Skeletal muscle contraction for balance
• Cerebellum
  • Coordinate balance and muscle tone
• Signal sent to thalamus
  • Relays to cerebral cortex
    • Awareness of body position

Chapter 6: Integumentary System

Layers of the Integument

• Epidermis
  • Keratinized stratified squamous epithelium
• Dermis
  • Predominantly dense irregular connective tissue
• Beneath is the subcutaneous (not part of integument)
  • Loose connective tissue
    • Adipose
    • Areolar

Layers of the epidermis - contain living keratinocytes

• Stratum basale - deepest
  • Keratinocytes
    • abundant, divide (mitosis),
    • synthesize keratin (strength for epidermis)
  • Melanocytes
    • produce and store melanin in response to UV light
  • Tactile cells
    • few and scattered
    • sensitive to touch
    • release a chemical for sensory nerve endings
• Stratum spinosum
  • Several layers of keratinocytes
    • non dividing
    • attached by desmosomes
    • Contains epidermal dendritic cells for immune response
• Stratum granulosum
  • 3-5 layers of keratinocytes
  • Keratinization begins
  • Keratinocytes fill with keratin
  • Cells die
• Stratum lucidum
  • 2-3 layers of dead keratinocytes
    • Cells filled with eleidin
      • Translucent protein, intermediate product
  • Only in thick skin
• Stratum corneum
  • 20-30 layers of dead interlocking keratinocytes
  • Completely keratinized
  • Dry thickened surface not suitable for microbial growth
  • Can protect against abrasion

Variations in the epidermis

• Thickness
  • Thick - contains 5 stratum layers
    • Palms of hands and soles of feet
    • Has sweat glands
    • No hair follicles
    • No sebaceous glands
  • Thin - contains 4 stratum layers
    • NO stratum lucidum
    • Most of body
    • Has sebaceous and sweat glands

Skin color

• Hemoglobin
  • oxygen binding protein, bright red in color
• Melanin - produced by melanocytes
  • We all have the same number of melanocytes
    • Dark- more active, more pigment
    • Light- temporarily altered, melanocytes activate in the sun (tanning)
  • Eumelanin
    • Brown or black shades
  • Pheomelanin
    • Lighter shades
• Carotene
  • yellow/orange pigment; keratinocytes and subcutaneous

Skin markings

• Nevus (mole)
• Freckles
• Hemangiomas - benign blood vessel tumors
  • Capillary hemangioma
    • brightened to deep purple nodule
  • Cavernous hemangioma
    • may last a lifetime
• Friction ridges
  • Large folds and valleys of dermis and epidermis

Layers of dermis

• Collagen fibers
• Blood vessels
• Sebaceous glands
• Nerve endings
• Arrector pili muscle
• Nail root
• Papillary layer
  • Superficial layer
  • Dermal papillae
  • Interlock with epidermal ridges - capillaries to epidermal cells and tactile cells
• Reticular layer
  • Collagen fibers extend in multiple directions

Lines of cleavage - tension lines

• Incisions perpendicular - slower healing
• Incisions parallel

Stretch marks

• Torn collagen fibers

Subcutaneous layer - interlocked in layers of dermis; stabilize skin position and binds to underlying structures

• Areolar connective tissue
• Adipose connective tissue
• Functions
  • Pads and protects body
  • Energy reservoir
  • Thermal insulation
  • Extensive vascular network
  • Thickness influenced by sex and hormones

Functions of integument

• Protection from external environment
  • Act as a physical barrier due to the many layers; injury, harmful substances, UV light, etc.
• Prevention of water loss and water gain
  • Epidermis is water resistant due to keratin
• Vitamin D synthesis
  • When keratinocytes are exposed to UV, they convert Vitamin D to calcitriol (increased Ca2+ retention)
• Secretion
  • Secrete sweat, waste products, sebum
• Absorption
  • Selectively permeable, are for transdermal passages for drugs
• Immune function
  • Epidermal dendritic cells
• Temperature regulation
  • Dermal blood vessels, vasodilation, vasoconstriction
• Sensory reception
  • Contain sensory receptors that detect external stimuli

Structures derived from epidermis

• Epidermal derivatives (embryonic development)

Nails - dead, keratinized cells formed on dorsal edges of fingers and toes

• Nail plate
  • Free edge
  • Nail body
  • Nail root
• Nail bed - layer of living epidermis covered by the nail body
• Nail matrix - actively growing area at the proximal end of nail body

Hair Types

• Keratinized cells grow from hair follicle that extends through the dermis
• Lanugo
  • fine, unpigmented downy hair that appears in the last trimester of embryonic development
• Vellus
  • Fine hair that replaces lanugo
  • Primary human hair
  • Locate on the upper and lower limbs
• Terminal
  • Coarse, pigmented, long
  • Located on the scalp, eyelashes, eyebrows, beard, pubic and axillary regions (puberty)

Zones along length

• Hair bulb
  • Swelling at the base
  • Origin of hair
  • Consist of living epithelial cells
  • Surround hair papilla
• Root
  • Bulb to below surface
• Shaft
  • Above surface to outer environment

Components

• Hair matrix
  • Epithelial cells divide here
  • Keratinization (death) of cells
• Hair follicle
  • Surround hair root going up
• Arrector pili muscle
  • Band of smooth muscle
  • Extend from hair follicle to dermal papilla

Hair functions

• Protection
  • Head
  • Nostrils
  • External ear canal
  • Eyelashes
• Heat retention
• Sensory reception
• Visual identification

Hair color

• Melanin
  • Synthesis occurs in hair matrix
• With age
  • Lightens
    • Pigment production decreases
  • Grey
    • Minimal melanin production
  • White
    • All melanin production stops

Hair growth and replacement

• Phases
  • Anagen
    • Active phase
    • Longer part of cycle
  • Catagen
    • Brief regression period
    • Cell division stops
    • Follicle undergoes involution
  • Telogen
    • Shedding of hair
    • Regrowth from hair bulb

Exocrine glands

• Mild epithelial cells that respond to sympathetic stimulation and release their contents
• Sweat glands
  • Simple, coiled secretory portion within the reticular layer
  • Merocrine
    • Most numerous
    • Onto skin surface
    • Sweat (99% water)
    • Help with thermoregulation
    • Allows water loss to eliminate waste and drugs
    • Dilutes harmful substances at the surface
  • Apocrine
    • Located at the axillary region, pubic/anal region and nipple region
    • Onto hair follicle
    • Viscous, cloudy secretion
    • Contains lipids and proteins that mix with bacteria causing odor (puberty)
• Sebaceous glands
  • • Holocrine glands (plasma membrane ruptures)
    • Onto hair follicle
    • Sebum - oily
      • Antibacterial substance that lubricates hair and scalp
      • Active at puberty due to sex hormones

Other integumentary glands - modified apocrine glands

• Ceruminous
  • External ear canal
  • Secrete ear wax that entrap foreign particles
  • Lubricate external acoustic meatus
• Mammary
  • Functions in pregnant and lactating females
  • Produces milk

Acne

• Plugged sebaceous gland ducts

Acne Lesions

• Comedo
  • Sebaceous gland clogged with sebum
  • Open - blackhead
  • Closed - white head
• Papule vs pustule - dome shaped lesions
  • Papule: fluid filled red elevations on the skin that contains no pus, that can turn into pustules
  • Pustule: contain leukocytes, dead skin cells, bacteria (pus)
• Nodule
  • Similar to pustules but fall deeper into the hair follicle
  • Prone to scarring
• Cyst
  • Severely inflamed that can lead to scarring

Tissue Repair

• Regeneration
  • Replacement of damaged or dead cells to restore tissue function
• Fibrosis
  • Gap filled with scar tissue
  • Contain collagen made from fibroblasts
  • For structural NOT functional repair

Stages of wound healing

• Cut vessel bleeds
  • Attract leukocytes and clotting proteins
• Blood clot forms
  • Barrier
  • Allow us to patch the wound
  • Allows neutrophils and macrophages to clean debris
• Cut vessel regenerates
  • Granulation tissue forms
    • Vascular connective tissue
    • Macrophages enter and remove clotted wound
    • Formation of a fibroblast to produce new collagen fibers
  • Epithelium regeneration
    • New cells migrate over the wound
    • Connective tissue replaced by fibrosis
    • Scabbing

Burns

• Fluid loss, infection, burned dead skin
• 1st degree
  • Redness, 3-5 days of healing
  • Epidermis only
• 2nd degree
  • Blisters, 2-4 weeks of healing, can lead to scarring
  • Epidermis and part of dermis
• 3rd degree
  • Hospitalization due to fluid loss and infection
  • Epidermis, dermis, and subcutaneous

Severity of burns

• Rule of nines
  • Used to estimates surface area of burn
  • Severe or critical burns
    • Over 25% of the body has 2nd degree burn
    • Over 10% of the body has 3rd degree burns on hands, feet, face, or perineum
• Degree of burn
• Age of patient
• Size of burn
• Location of burn

Aging of integument

• Skin changes color
  • Reduced number and activity of stem cells
    • Repair process slows
  • Fewer collagen fibers
  • Elastic fibers lose elasticity
  • Decrease immune response
  • Hair follicle produce thinner hair
• Smoking and UV radiation
  • Damages DNA in epidermal cells
    • Accelerates aging
    • Skin cancer
      • Basal cell carcinoma (most common)
        • At stratum basale layer
        • Common on the face
      • Squamous cell carcinoma
        • At the keratinized stratum spinosum layer
        • Lesions on scalp, ears, lower lip, dorsum of hand
        • Can spread
      • Malignant melanoma (most deadly)
        • Melanocytes
        • Occurs in a preexisting mole
        • Aggressive

Chapter 18: Blood

Fluid connective tissue

• Transported by the cardiovascular system
  • Arteries
  • Veins
  • Capillaries
• Formed element in plasma matrix
  • Erythrocytes
  • Leukocytes
  • Platelets

Functions of blood

• Transportation
  • Respiratory gasses
  • Formed elements
  • Hormones
  • Nutrients
  • Waste
• Regulation of body conditions
  • Body temperature
    • Absorb heat and release heart at the skin
  • Body pH
    • Can absorb acids and bases
    • Has buffers to maintain normal pH range
  • Fluid balance
    • Add water through GI tract
    • Lose water in skin, urinary tract, respiration
    • Exchange between blood and interstitial fluid
• Protection
  • Leukocytes
  • Plasma proteins
  • Platelets

Characteristics of blood

• Color
  • Degree of oxygenation
    • High oxygen: bright red
    • Low oxygen: deep red
• Volume
  • About 5L
• Viscosity
  • 4-5 times more viscous than water
  • Depends on the dissolved and suspended substances
  • High erythrocytes = high viscosity
  • Low fluid levels = high viscosity
• Plasma concentration
  • Concentration of solutes
  • Direction of osmosis in capillary wall
• Temperature
  • 1 degree (celcius) higher than body temperature
• pH
  • Between 7.35-7.45
  • Slightly alkaline
  • If altered plasma protein becomes denatured

Components of blood

• Plasma - 55%
• Formed elements
  • Buffy coat - 1%
    • Leukocytes
    • Platelets
  • Erythrocytes - 44%
• Hematocrit - percentage of erythrocytes
  • Adult males 42-56%
    • Higher due to testosterone, stimulate kidney to produce EPO to increase RBC production
  • Adult females 38-46%
  • High levels
    • Dehydration
    • In athletes, due to blood doping
  • Low levels
    • Anemia
    • Hemorrhage

Plasma components

• Water (92%)
• Plasma proteins (7%)
  • Exert colloid osmotic pressure
  • Albumin
  • Globulins
  • Fibrinogen
  • Regulatory proteins
• Dissolved molecules and ions, nutrients, hormones, vitamins, enzymes, and waste products (1%)

Plasma proteins

• Albumins
  • Most abundant (58%)
  • Greatest colloid osmotic pressure
  • Produced in liver
  • Control osmotic pressure with Na+
  • Transports hormones, ions, and some lipids
• Globulins
  • 37%
  • Alpha and beta
    • Transport some water insoluble molecules, hormones, and metals and ions
  • Gamma
    • Antibodies
• Fibrinogen
  • 4%
  • Produced by liver
  • Crucial in blood clotting
  • Soluble form of fibrin
• Regulatory proteins
  • <1%
  • Hormones and enzymes

Other solutes in blood

• Electrolytes
  • Cl- and Na+ or K+
• Nutrients
  • Glucose, amino acids, lactic acid, lipids (CHO, HDL, LDL, triglycerides, phospholipids
• Respiratory gasses
  • Oxygen and carbon dioxide
• Wastes
  • Urea, creatinine, bilirubin, ammonia

Hematopoiesis - occur in red bone marrow

• Hemocytoblast - multipotent stem cell
  • Myeloid line
    • Erythropoiesis
      • Erythrocytes

1. The myeloid stem cell under the influence of multi-CSF forms a progenitor cell. EPO hormone will increase rate of production
2. Progenitor cell forms a proerythroblast (large and nucleated)
3. Proerythroblast becomes an erythroblast which has ribosomes that produce the hemoglobin protein
4. A large erythroblast will form a normoblast - a small cell with more hemoglobin and an ejected nucleus
5. Formation of a reticulocyte - only ribosomes to synthesize hemoglobin
6. Reticulocyte matures into an erythrocyte - which only contains hemoglobin as ribosomes have degenerated
   • • Leukopoiesis
       • Leukocytes
7. Myeloid stem cell is stimulated by multi-CSF and GM-CSF to form a progenitor cell
8. Granulocyte line develops when the progenitor cell forms a myeloblast under the influence of G-CSF.
   1. This will differentiate into granulocytes (eosinophil, basophil, neutrophil)
9. Monocyte line develops when the progenitor cell forms a myeloblast under the influence of M-CSF
   1. This will differentiate into a monocyte
   • Lymphoid line
     • Leukopoiesis
       • Lymphocytes
       • Natural killer T cell
10. Lymphoid stem cell will differentiate into either a B-lymphoblast or T-lymphoblast
    1. B-lymphoblast will mature into a B-lymphocyte
    2. T-lymphoblast will mature into a T-lymphocyte
11. Some will differentiate into a natural killer cell directly

• Hemocytoblast
  • Myeloid line
    • Thrombopoiesis
      • Megakaryocyte
      • Platelets

1. From the myeloid stem cell, a committed cell called a megakaryoblast is produced
2. It matures under the influence of thrombopoietin to form a megakaryocyte
3. Megakaryocytes produce platelets by forming long extensions from themselves called proplatelets
   1. These proplatelets extend through the blood vessel wall in the red bone marrow
   2. The force from the blood flow “slices” these proplatelets into the fragments we know as platelets
4. Megakaryocytes remain within the red bone marrow, whereas the cellular fragments that become platelets enter the blood

Erythrocytes

• Small, flexible formed element
• Biconcave disc
  • Surface area
  • Allows stacking
• Transports
  • Oxygen and carbon dioxide

Hemoglobin

• Four protein molecules called globins
  • 2 alpha
  • 2 beta
• All contain heme group - each alpha/beta chain has this
  • Porphyrin ring
  • Iron ion - in the center of porphyrin ring
    • Where oxygen forms a weak bond for easy attachment/detachment
  • Globin molecule
    • Where carbon dioxide forms a weak bond for easy attachment/detachment

EPO Regulation of Erythrocyte Production

• Produced in kidneys
• Secretion release stimulated by decrease in blood oxygen levels
• Causes: removal of aged RBC, blood loss

Negative Feedback:

1. Chemoreceptors in kidney detect low blood oxygen levels
2. EPO released
3. EPO travels to red bone marrow
4. Erythrocytes are stimulated from myeloid stem cells
5. Blood oxygen levels go up
6. Increased blood oxygen levels inhibit EPO release

Higher rate in males due to testosterone

Recycling and Elimination of Erythrocytes

• Aged erythrocytes - 120 day lifespan
  • Cannot repair - no organelles
  • Phagocytized by macrophages - in the liver and spleen
  • Hemoglobin components separated
    • Globin proteins
      • Get broken down into amino acids that enter blood to synthesize protein
    • Iron ion
      • Transferrin
        • Transports iron ion to liver and spleen (storage)
    • Heme group - converted within macrophages to (below)
      • Biliverdin - green pigment
        • Bilirubin - yellow pigment
        • Transported by albumin to the liver
        • Released as a component of bile to the small intestine converted to urobilinogen

Urobilinogen

1. Small intestine to large intestine
   1. Converted by bacteria to stercobilin (brown pigment)
   2. Expelled in feces
2. Absorbed back into the blood
   1. Converted to urobilin (yellow pigment)
   2. Excreted by urine

Erythrocyte disorders

• Anemia
  • Aplastic
    • Decrease in formation of erythrocytes and hemoglobin due to defective bone marrow
    • Bone marrow cannot produce erythrocytes
  • Congenital hemolytic
    • Genetic defect
    • Abnormal membrane proteins cause a fragile plasma membrane
    • Causes destruction of erythrocytes
  • Erythroblastic
    • Heredity
    • Large number of immature nucleated cells
    • Causes abnormal acceleration
  • Hemorrhagic
    • Blood loss
    • Chronic ulcers
    • Heavy menstrual flow
  • Pernicious
    • Failure to absorb vitamin B12
    • Lack an intrinsic factor
  • Sickle cell anemia
    • Genetic defect
    • Autosomal recessive anemia
    • Red blood cell is sickle shaped with lower oxygen levels
    • Cannot flow seamlessly to vessels

ABO Blood Group

• Erythrocytes
  • Surface Antigen
    • ABO
    • Rh
  • Antibody
    • Anti-A antibody
    • Anti-B antibody

Rh factor

• Surface Antigen D - positive or negative

Rh Incompatibility

• Rh negative mother
  • Rh positive fetus
• 1st Pregnancy:
  • Antigen D introduced to mother’s blood
• Between pregnancies:
  • Anti-D antibodies produced in the mother
• 2nd Pregnancy:
  • Anti-D antibodies attack Rh+ fetal erythrocytes
• Treatment:
  • Immunoglobulins
  • Bind to antigens so mom doesn’t make antibodies

Clinical considerations about blood types

• Agglutination reaction
  • Clumped cells block blood vessels
  • Cause hemolysis
    • Lead to organ damage

Leukocyte Characteristics

• Defend against pathogens
• Motile and flexible
  • Diapedesis - leukocytes squeezed thru endothelial cells of blood vessel wall
  • Chemotaxis - release of chemicals to attract leukocytes
• Two classes
  • Granulocytes - basophil, eosinophil, neutrophils
  • Agranulocytes - lymphocytes and monocyte

Granulocytes

• Neutrophil
  • Most numerous (50-70%)
  • Light purple granules
  • Multilobed
  • Phagocytose pathogens during bacterial infections
• Eosinophil
  • 1-4%
  • Bilobed nucleus
  • Reddish granules
  • Go after antibody-antigen complexes and allergens
  • Attack parasitic worms via apoptosis
• Basophil
  • 0.5-1%
  • Bilobed nucleus
  • Dark purple granules
  • Histamine (vasodilator), heparin (anti-coagulant)

Agranulocytes

• Monocytes
  • 2-8%
  • C-shaped nucleus
  • Exit blood to reside in tissues
  • Transform into macrophages that phagocytize bacteria, dead cells, viruses, cell fragments, etc.
• Lymphocytes
  • 20-40%
  • Dark stained nucleus
• T-Lymphocytes
  • Manage and direct immune response
  • Go after foreign cells
• B-Lymphocytes
  • Become plasma cells
  • Produce antibodies
• Natural Killer
  • Apoptosis inducing cells against abnormal cells or infected tissues

Platelets (Thrombocytes)

• Irregular shape
• From megakaryocytes
• Role in homeostasis

Hemostasis

1. Vascular spasm - blood vessel constricts to limit blood loss
   1. Limits blood leakage
   2. Platelets and endothelial cells release chemicals for further constriction
2. Platelet plug formation - platelets arrive at site of injury and adhere to exposed collagen fibers
   1. Platelets change and adhere
      1. Von Willebrand factor - platelets swell and become sticky - adhere to collagen fibers - mitosis stimulating substances releases - repair of blood vessel wall.
   2. Release chemicals - prolong vascular spasm and attract more platelets
      1. Serotonin
      2. Thromboxane A2
      3. ADP
      4. Procoagulants
   3. Thrombocytopenia
      1. Low platelet count
3. Coagulation phase - coagulation cascade converts inactive proteins to active forms, which ultimately form fibrin strands of a blood clot
   1. Network of fibrin (from fibrinogen) forms mesh (fibrin network, trapped RBC, platelets, WBC, plasma proteins)
   2. Clotting requires
      1. Calcium
      2. Clotting factors
      3. Platelets
      4. Vitamin K - synthesis of clotting factors 2, 7, 9, 10
   3. Clotting begins with two pathways
      1. Intrinsic pathway (inside) - platelets adhere to vessel wall - various factors releases - factor IX binds with Ca2+ and platelet factor III - complex - active factor VIII - activate factor X
      2. Extrinsic pathway (outside) - release of tissue thromboplastin - combines with factor VII and Ca2+ - complex activates factor X
   4. Both pathways converge to one common

• Factor X - prothrombin activator - prothrombin - thrombin (enzyme) - thrombin - fibrinogen - fibrin threads (mesh)

Elimination of the clot

• Clot reaction
  • Actinomyosin contracts - squeeze serum out of clot - vasoconstriction
• Fibrinolysis
  • Plasmin - enzyme that digest fibrin

Bleeding Disorders

• Hemophilia
  • Hemophilia A - lack factor 8
  • Hemophilia B - lack factor 9
  • Hemophilia C - lack factor 11
• Vitamin K deficiency
• Thrombocytopenia - low platelet count

Blood clotting disorders

• Hypercoagulation - tendency to clot
  • Thrombus - clot
  • Embolus - clot is dislodged

Chapter 19: Heart

Cardiovascular System

• Function
  • Transport blood, nutrients, and carbon dioxide
  • Maintain adequate perfusion - sufficient delivery of nutrients to cells

Components of Cardiovascular System

• Blood vessels
  • Arteries - away
  • Capillaries - exchange
  • Veins - towards
• Heart - 4 chambers, 2 pumps

Anatomic Features of the Heart

• 2 sides
  • Right side
    • Right atrium - receive deoxygenated blood from the body
    • Right ventricle - pumps deoxygenated blood to lungs
  • Left side
    • Left atrium - receives oxygenated blood from lungs
    • Left ventricle - pumps oxygenated blood to body
• Great vessels
  • Right side
    • SVC and IVC - drain deoxygenated blood into right atrium
    • Pulmonary trunk - receive deoxygenated blood pumped from right ventricle
  • Left side
    • Pulmonary veins - drain oxygenated blood into left atrium
    • Aorta - receives oxygenated blood pumped from left ventricle
• Valves
  • Right side
    • Right AV valve - between right atrium and right ventricle
    • Pulmonary semilunar valve - between right ventricle and pulmonary trunk
  • Left side
    • Left AV valve - between left atrium and left ventricle
    • Aortic semilunar valve - between left ventricle and aorta
  • AV valves close when ventricles contract
  • Semilunar valves open when ventricles contract

Circulation Routes

• Pulmonary Circulation
  • Deoxygenated blood enters the right atrium from the IVC and SVC and coronary sinus
  • Blood passes through the right AV valve
  • Blood enters right ventricle
  • Blood passes through the pulmonary semilunar valve
  • Blood enters pulmonary trunk
  • Blood continues through the right and left pulmonary arteries to both lungs
  • Blood enters pulmonary capillaries of both lungs for gas exchange
  • Oxygenated blood exits the pulmonary capillaries of the lungs and returns to the heart by right and left pulmonary veins
  • Blood enters the left atrium of the heart
• Systemic circulation
  • Oxygenated blood enters the left atrium
  • Blood passes through the left AV valve
  • Blood enters the left ventricle
  • Blood passes through the aortic semilunar valve
  • Blood enters the aorta
  • Blood is distributed by the systemic arteries
  • Blood enters systemic capillaries for exchange
  • Deoxygenated blood exits systemic capillaries and returns to the heart by systemic veins
  • Drain into IVC, SVC, coronary sinus
  • Blood enters right atrium

*Coronary Circulation*

• Coronary Arteries
  • Right coronary artery
    • Right marginal artery - feed lateral wall of right ventricle
    • Posterior interventricular artery - feed posterior wall of both ventricles
  • Left coronary artery
    • Circumflex artery - feed lateral wall of left ventricle
    • Anterior interventricular artery - feed anterior wall of left ventricle and interventricular septum
• Coronary veins
  • Transport deoxygenated blood from heart wall to heart (drain to coronary sinus)
    • Great cardiac, middle cardiac, small cardiac

Microscopic Anatomy of Cardiac Muscle (myocardium)

• Sarcolemma
• T-tubules
• Sarcoplasmic reticulum
  • Surrounds bundles of myofilaments - arranged in sarcomeres
• Intercalated discs - cells connect by this
  • Desmosomes - mechanical connection of cells
  • Gap junctions - ion flow

Metabolism of Cardiac Muscle

• Extensive blood supply
• Numerous mitochondria
• Myoglobin - bind oxygen at muscle rest
• Creatine kinase - catalyze creatine phosphate
• Able to use different fuel molecules
• Relies on aerobic cellular respiration
  • Rely on oxygen, susceptible to failure in low oxygen conditions - lead to cell death (myocardial infarction)

Heart Conduction System - ANS influence

• Sinoatrial node
  • Initiate heartbeat
• Atrioventricular node
  • Located in floor of right atrium
• Atrioventricular bundle
  • Extends from AV node
  • Divides into left and right bundles
• Purkinje fibers
  • Extends from left and right bundles at apex

Innervation of Heart

• Cardiac center (medulla oblongata)- rate/strength of contractions
  • Signaled by chemoreceptors and baroreceptors
• PNS - decrease HR
  • Cardioinhibitory center
  • Vagus nerve
    • Right vagus innervates SA node
    • Left vagus innervates AV node
• SNS - increase HR
  • Cardioacceleratory center
  • Cardiac nerves through T1-T5 segments of spinal cord
    • Extend to SA node, AV node, myocardium, and coronary arteries
    • Promote vasodilation - blood flow to myocardium

Heart Contraction

• Conduction system
  • Initiation - SA node initiates an action potential
  • Spread of action potential - throughout atria and conduction system
• Cardiac muscle cells
  • RMP: -90mV
  • Action potential propagated along sarcolemma of cardiac muscle cells
  • Muscle contraction - thin filaments slide past thick filaments and sarcomeres shorten within cardiac muscle cells
• SA nodal cells
  • Pacemaker cells - initiate a heartbeat via depolarization
  • Generate AP
  • RMP = -60mV

Electrical Events at SA node - spontaneous depolarization

• Initiation of action potential
• RMP: -60mV
• Reaching threshold - allow influx of Na+ (-60mV to -40mV)
• Depolarization - fast voltage gated Ca2+ channels open (-40mV to 0mV)
• Repolarization - voltage gated K+ channels open (0mV to -60mV)
• @ rest: SA node starts an action potential after 0.8 secs after the last one
  • Resting rate: 70 bpm
  • Fire faster but don’t due to vagal tone (by PNS)

Spread of action potential

• Generated at SA node - spread to gap junctions throughout atria to AV node - action potential delayed at AV node - AV bundle conducts the action potential along the left and right bundle branches to purkinje fibers - action potential is spread via gap junctions throughout ventricles

Electrical Events of Cardiac Muscle Cells

• Action potential opens fast voltage gated Na+ channels - depolarization (-90mV to 30mV) - channels close - plateau (K+ in, Ca2+ out) - repolarization (K+ out, 30mV to -90mV) - RMP

Mechanical Events of Cardiac Muscle Cells

• Ca2+ from SR and interstitial fluid used for crossbridge cycling - Ca2+ binds to troponin - crossbridge, powerstroke, release of myosin head, reset of myosin head

Refractory Period

• Longer in cardiac muscle - cannot exhibit tetany - can’t fire another action potential during refractory period (plateau)

ECG

• Waves
  • P wave - atrial depolarization
  • QRS complex - ventricular depolarization
  • T wave - ventricular repolarization
• Segments
  • PQ segment - atrial plateau
  • ST segment - ventricular plateau
• Intervals
  • P-R interval - time needed to transmit action potential to entire conduction system
  • Q-T interval - time required for AP to occur in ventricles

Cardiac Cycle

• Atrial relaxation/ventricular filling
  • Chambers relaxed - blood return to atrium - passive filling of ventricles - arterial BP>>ventricular BP - semilunar valves close - AV valves open
• Atrial contraction/ventricular filling
  • SA nodes are stimulated - push remaining blood into ventricles - filled to EDV (vol. Of blood within ventricle @ end of diastole, 130mL)
• Isovolumic contraction
  • Purkinje fibers start ventricular contraction - ventricular pressure rises - AV valves close
• Ventricular ejection
  • Semilunar valves open - SV (amount of blood ejected by each ventricle 70mL) - ESV (remaining blood in ventricle after contraction, EDV-SV)
• Isovolumic relaxation
  • Ventricles relax - arterial pressure>>ventricular pressure - semilunar valves close

Cardiac output

• Amount of blood pumped by a single ventricle in one minute (L/min)
• Determined by heart rate and stroke volume
  • HR x SV = CO (75 bpm x 70mL/beat = 5.25L/min)
• Function of HR and SV - maintain resting CO
  • Increased by exercise
  • Small heart = small SV - higher bpm
  • Big heart = large SV - low bpm

Cardiac reserve

• Level of exercise a person can endure
• Increase in cardiac output above its resting level
• Subtract CO at rest from CO during exercise

Variables that Influence HR

• Positive chronotropic agents - increase HR
  • SNS - release NE (hormone and NT) - act on SA nodal cells - adrenal medulla release its hormones -
  • TH - increase number of beta-1 receptors (for NE/EPI)
  • Nicotine - increase release of NE - beta-1 receptors
  • Caffeine - inhibit breakdown of cAMP
  • Cocaine - inhibit reuptake of NE
• Negative chronotropic agents - decrease HR
  • PNS - Ach release on nodal cells - bind to muscarinic receptors - hyperpolarization - slow HR
  • Beta blockers - interfere with binding of EPI and NE on to beta-1 receptors - slow HR
• Autonomic reflexes
  • Atrial reflex - prevent heart from overfilling
    • Stimulated by increased venous return - cardiac center - cardioacceleratory center - SNS - increase HR - lessen stretch on atrial walls

Variables that Influence Stroke Volume

• Venous return - blood returned to heart per unit time
  • Frank-Starling Law - the more blood put in, the more it will stretch - great overlapping of filaments - greater crossbridge formation - increased SV
  • Increase
    • Increase venous pressure (exercise)
    • Increased time (to fill ventricles)
  • Decrease
    • Low blood volume (hemorrhage)
    • High heart rate - small EDV - small preload - small SV
• Inotropic agents - substances that act on the myocardium to alter contractility
  • Positive - increase available Ca2+/cross bridges
    • SNS - NE/EPI - beta-1 receptors - increase Ca2+
    • TH - increase beta-1 receptor in cardiac muscle cells
    • Drugs - digitalis - boost CO by increasing contractility
  • Negative - decrease available Ca2+/cross bridges
    • Electrolyte imbalance
    • Drugs
• Afterload - resistance in arteries to ejection of blood
  • Atherosclerosis - narrow lumen - increase peripheral resistance - decrease SV

Variables Affecting Cardiac Output

• Chronotropic agents, venous return, inotropic agents, after load
• Increase SV and HR = increase CO
• Decrease SV and HR = decrease CO

Chapter 20: Vessels/Circulation

Anatomy and Physiology of Blood Vessels

• 3 Types
  • Artery, capillary, vein
• 3 layers
  • Tunica intima, tunica media, tunica externa

Comparison of Different Vessel Types

• Arteries
  • Elastic - conducting from the heart to muscular arteries
  • Muscular - distributing blood to the organ
  • Arterioles - undergo vasomotor tone
• Capillaries
  • Continuous - skin, lungs, CNS, muscles
  • Fenestrated - pores - SI, kidneys, choroid plexus
  • Sinusoid - liver, spleen, red bone marrow, endocrine glands
  • Diffusion of solutes
  • Vesicular transport - pinocytosis, exocytosis
  • Bulk flow - movement of large amounts of fluid and dissolved substances, down a pressure gradient
    • Filtration - fluid moves out of the blood - on arterial end
    • Absorption - fluid moves into the blood - on venule end
  • Blood hydrostatic pressure - force exerted per unit of area by the blood on vessel wall - arterial end, greater than blood colloid osmotic pressure
  • Blood colloid osmotic pressure - promote reabsorption (in) - oppose hydrostatic pressure - greater in venous end to promote reabsorption
• Veins
  • Venules
  • Small-medium - valves
  • Large - valves
  • Systemic veins - blood reservoirs that can move out of circulation during activity

Pathways of Blood Vessels

• Simple Pathways - 1 major artery delivers blood to organ or region
• Alternative Pathways
  • Anastomosis - joining of blood vessels
    • Arterial (2 or more aa. join), venous (2 or more vv. drain), arteriovenous (shunt)
  • Portal system - 2 capillary beds in sequence
    • Arteriole - capillary bed - portal vein - capillary bed - vein

Factors of local blood flow

• Degree of vascularization
  • Angiogenesis - blood vessels create new ones in the tissue - exercise, weight gain
  • Regression - return to the previous state before angiogenesis
• Myogenic response - constant blood flow
  • BP rises - more blood in the arteriole - stretches - smooth muscle of arterial wall will constrict vessel
  • BP lowers - less blood in arteriole - less stretch - smooth muscle of arterial wall relaxes vessels
• Local regulatory factors
  • Vasodilators - dilate arterioles, relax precapillary sphincters - increase blood flow in capillary bed
  • Vasoconstrictors - constrict arterioles - contraction of precapillary sphincters - decrease blood flow in capillary bed
  • Autoregulation - inadequate perfusion - vasodilators activated - increase blood flow in capillary bed - adequate perfusion
  • Short-term regulation (immunity) - endothelial cells release nitric oxide (vasodilator) and thromboxane (vasoconstrictor)
• Total blood flow
  • May increase with exercise
  • Depends on both heart and vessels

Blood Pressure: force per unit area that blood exerts against the inside wall of a vessel

Blood pressure gradient: change in pressure from one end of the vessel to the other - propel blood through the vessels - high in arteries - low in veins

Arterial blood pressure: blood flow in arteries that pulses cardiac cycle

• Systolic - max stretch of artery
• Diastolic - recoil of artery
• Pulse - systolic/diastolic - additional pressure placed on arteries by heart contraction

Venous Blood Pressure:

• Venous return - depend on BP gradient
  • Skeletal muscle pump - moves blood during physical activity
  • Respiratory pump - venous return in thorax

Peripheral Resistance: amount of friction blood experiences traveling through blood vessels

• Viscosity - resistance of fluid to its flow - less = less resistance; more = more resistance
• Vessel length - the longer the vessel, the greater the resistance
• Vessel radius - smaller radius = more resistance; bigger radius = less resistance

Regulation of Blood Pressure and Flow (ANS)

• BP decrease
  • Baroreceptors sense decreased stretch - decrease firing rate sent to cardiac and vasomotor centers – cardioacceleratory center increases nerve signals; cardioinhibitory center decreases nerve signals - vasomotor center increases nerve signals - vasoconstriction - increase peripheral resistance
• BP increase
  • Baroreceptors sense increased stretch - increase firing rate to cardiac and vasomotor centers - cardioacceleratory center decreases nerve signals; cardioinhibitory center increases nerve signals - vasomotor center decreases nerve signals - vasodilation - decrease peripheral resistance

Chemoreceptor Reflexes

• Aortic (vagus) and carotid (glossopharyngeal) bodies - send signals to cardiovascular center
• Stimulated by high CO2, low pH, very low 02 - increases firing rate to cardiovascular center
• Vasomotor center - increases SNS to veins and increases venous return - increase blood flow including to lungs

Higher Brain Centers

• Hypothalamus - increase CO and resistance
  • Temp increase - high BP
  • Fight or flight - high BP
• Limbic system - alter BP in response to emotional memories

Renin-Angiotensin System

• Kidney detects low BP or stimulated by SNS, renin enzyme released - renin converts angiotensinogen to angiotensin I - ACE converts angiotensin I into angiotensin II - angiotensin II increases BP by - vasoconstriction, stimulate thirst center, decreased urine formation - releases ADH and aldosterone
• Aldosterone: triggered by angiotensin II - increased H20 and Na+ in kidneys - decrease urine output
• ADH: triggered by angiotensin II - increases H20 absorption - maintain blood volume - stimulate thirst centers
• ANP: released due to increased stretch of heart atria - stimulates vasodilation - decrease resistance - increase urine output to lower blood volume

Blood Flow Distribution During Exercise

• Increase - stronger, faster heartbeat - skeletal muscles help remove blood from reservoirs
• Redistribution - according to needs of tissues

Pulmonary Circulation

• Pulmonary arteries
  • Less elastic CT
  • Wider lumens
• Pulmonary vessels
  • Shorter than systemic BP
  • Lower BP

Hepatic Portal System

• Blood from digestive organs sent to liver - blood returned to heart
• Hepatic portal vein drains from - splenic vein - inferior mesenteric vein - superior mesenteric vein

Fetal Circulation

• Fetal lungs - non functional
• Fetal vessels - shunt blood to organs in need
• Route
• Oxygenated blood from placenta enters fetus through umbilical veins (round ligament of liver)
• Blood sent to IVC via ductus venosus (ligamentum venosum)
• Mixing of oxygenated blood and deoxygenated blood
• Blood from IVC and SVC empty in right atrium
• Blood shunted to L atrium via foramen ovale (fossa ovalis)
• Small amount enters right ventricle, pumped to pulmonary trunk
• Shunted to aorta through ductus arteriosus (ligamentum arteriosum)
• Blood travels to body and returns to placenta through umbilical arteries (medial umbilical ligaments)

Chapter 21: Lymphatic System

Functions

• Transport and house lymphocytes and other immune cells
• Return excess interstitial fluid to the blood

Components:

• Lymph vessels
• Lymphoid tissues
• Lymphoid organs
• Lymph (fluid) - water, dissolved solutes, protein, foreign material, cancer cells

Lymph capillaries

• Close-ended
• Occur everywhere except red bone marrow and avascular tissues
• Resemble blood capillaries
• Lacteals - SI

Movement of lymph into lymph capillaries

• Hydrostatic pressure - push lymph fluid into openings
• Anchoring filaments - prevent from collapsing

Lymphatic vessels

• Capillaries merge to form
• Adjacent to arteries and veins
• Resemble veins
• Rely on respiratory/skeletal muscle pumps, pulsatile movement of blood and nearby arteries, rhythmic contraction of smooth muscle

Lymphatic Trunks

• Jugular trunks - drain from head and neck
• Subclavian trunks - drain upper limbs, breast, superficial thoracic walls
• Bronchomediastinal trunks - drain deep thoracic structures
• Intestinal trunks - drain most of abdominal structures
• Lumbar trunks - drain lower limbs, abdominal and pelvic walls, pelvic organs

Lymphatic Ducts

• Right lymphatic duct
  • Drains upper right quadrant of body
  • Delivers to junction of right subclavian and right internal jugular vein
• Thoracic duct
  • Drains from left side of head and neck, left upper limb, left side of thorax, abdomen , and both lower limbs
  • Delivers to junction of left subclavian and left jugular veins
• Cisterna chyli
  • Receive lipid rich chyle from GI tract
  • Both lumbar and intestinal trunks drain into this

Lymphoid Tissues and Organs

• Primary lymphoid structures
  • Formation and maturation of lymphocytes
  • Red bone marrow (hematopoiesis) , thymus
• Red Bone Marrow:
  • Hematopoiesis
  • B-cells:mature in bone marrow
  • T-cells: migrate to thymus and matures in thymus
• Thymus:
  • T-lymphocyte maturation and differentiation
  • Inner medulla - mature T cells
  • Outer cortex - immature T cells
• Secondary lymphoid structures
  • House lymphocytes and other immune cells - Site of immune response initiation
  • Lymph nodes, spleen, tonsils, MALT
• Lymph nodes:
  • Afferent (many) and efferent (one) lymphatic vessels
  • Capsule
  • Outer cortex
    • Germinal center - house proliferating B cells and macrophages
    • Mantle zone - T cells, macrophages, dendritic cells
    • Cortical sinuses - tiny channels lined by macrophages
  • Inner medulla
    • Medullary cords - CT fibers that support T and B cells and macrophages
    • Medullary sinuses - tiny channels lined by macrophages
• Spleen:
  • White pulp - monitor foreign substances
  • Red pulp - store RBC and platelets
• Tonsils:
  • Immune surveillance for anything we inhale or ingest
  • Pharyngeal, palatine, lingual
• Lymphoid nodules:
  • Clusters of lymphoid cells
  • Walls of appendix and body organs
  • Defend against infections
• MALT:
  • Prominent in SI
  • Peyer patches
  • Prominent in lamina propria of mucosa layers

Chapter 22: Immune System

Infectious agents - causes damage of a host

• Five categories
  • Bacteria
    • Single cell prokaryotes
    • Plasma membrane
    • Cell wall
    • *virulent (illness)
      • Pilli
      • Capsule
      • Toxins
  • Viruses
    • Smaller than bacteria
    • Pieces of DNA or RNA inside a protein capsid
    • Need to enter cell to reproduce
    • *Viral particles
    • Ex. HIV, SARS, COVID, varicella
  • Fungi
    • Eukaryotic cells
    • Plasma membrane
    • Cell wall
    • Mold, yeast, spores
    • Proteolytic enzymes
      • Inflammations that affect mucosal lining
  • Protozoans
    • Eukaryotic cells
    • Plasma membrane
    • NO cell wall
    • Intracellular/extracellular parasites that interfere with normal cell function
    • Ex. malaria
  • Multicellular parasites
    • Larger
    • Reside and take nourishment from the host
    • Ex. tapeworms, pinworms
• Prions
  • Small fragments of infectious proteins
  • Disease in nervous tissue
  • Creutzfeldt-Jakob disease
    • Human variant

Immune System

• Cellular and molecular structures which function together in the body’s defense
  • Innate immunity
    • Present at birth
  • Adaptive immunity
    • Acquired or specific immunity

Cytokines

• Chemical messengers
  • Small soluble proteins that regulate immune activity (both innate and adaptive)

1. Communication between cells
2. Control development and behavior of immune cells
3. Regulate inflammatory response
4. Function to destroy cells
   • Short ½ life to prevent constant stimulation
   • Released from one cell and bind to specific receptors
   • Autocrine
     • Act on cell that released them
   • Paracrine
     • Act on a neighboring cell
   • Endocrine
     • Act on distant cells after circulating in blood

Innate Immunity

• First line of defense
  • Skin
    • Release antimicrobial substances like sebum
    • Lysozymes: antibacterial enzyme that’ll attack cell walls
    • Dermasidant: antibacterial, antifungal
    • Normal flora: prevent pathogen growth
  • Mucosal membranes
    • Release mucus
    • Antimicrobial substances
    • Lysozymes
    • Defendants: pores in membranes of microbes
    • IgA: specific antibody
    • Locations:
      • Respiratory tract (cilia) - coughing and sneezing
      • GI tract (saliva, HCl)
      • Urogenital system (urine
      • Vagina (low pH)
• Second line of defense
  • Internal processes
    • Activities of immune cells
    • Physiological processes
    • Inflammation
    • fever

Nonspecific (INNATE) Internal Defenses

Cells: can recognize certain receptors

• Neutrophils, Macrophages, Dendritic cells (antigen-presenting cells, fragments on plasma membrane that present to T-lymphocytes for adaptive immunity)
  • Vesicle within unwanted substance
  • Merge with lysozyme
  • Breakdown substance
  • Respiratory burst
    • Reactive oxygen-containing molecules that destroy microbe
  • Leftovers are exocytosed
• Basophils (in circulation), Mast cells (reside in CT of skin and mucosal linings)
  • Proinflamatory
  • Chemotaxic (attract immune cells)
  • Eicosanoids (inflammation)
• Natural Killer cells
  • Apoptosis inducing cells
  • Immune surveillance
  • Destroy virus infected cells and tumors
  • Perferrin:
    • Transmembrane pores on plasma membrane
    • Release granzymes - enter pores to induce apoptosis
• Eosinophils
  • Parasites
  • Allergies
  • Asthma
  • Phagocytize antigen-antibody complexes
  • Target multicellular parasites
  • Degranulated to release enzymes and toxins
  • Transmembrane pores
• Antimicrobial proteins
  • Function against microbes
• Interferons (IFN)
  • Cytokines
  • Nonspecific defense against viruses and intracellular bacteria
  • Physiology:

1. Virus enters system
2. Cell releases IFN-alpha and IFN-beta
   1. Stimulate NK cells
   2. Destroy virus infected cells
   3. Apoptosis
   4. Release IFN-gamma to stimulate macrophages to virus infected cell
3. IFN-alpha and IFN-beta attach to the receptors of local cells
4. Local cell will synthesize enzyme that will destroy RNA or DNA
5. Prevents cell from being attacked by viruses

• Complement system
  • Group of >30 proteins that work along complement antibodies-
    • Produced in liver
    • Released in inactive form
    • Activated by enzyme cascade that causes pathogen entry
    • Complements activated:

1. Classical
   1. Antibody to foreign substance
   2. Complement binds to antibody
2. Alternative: complement bind to polysaccharide of bacterial fungal cell wall.
   1. Inflammation
      1. Enhanced by complement
      2. Increase mast cell, basophil, neutrophil, macrophage activity
   2. Opsonization
      1. Complement protein bind to pathogen
      2. Enhance phagocytosis
   3. Cytolysis
      1. Complement trigger splitting of target cell
      2. Complement cell forms MAC - create channel in membrane fluid inside to induce cytolysis
   4. Elimination
      1. Complement linking erythrocytes to antigen-antibody complex
      2. Erythrocytes to liver and spleen where the complex is stripped off.

Inflammation

• Immediate local response
• Innate immunity
• In vascularized tissue to remove unwanted substances
• Events of Inflammation

1. Release of inflammatory and chemotactic factors (note: they attract immune cells)
2. Vascular changes
   1. Vasodilation in arterioles lead to increased permeability
   2. Increased endothelial expression of molecules for leukocyte adhesion
   3. Display of CAMs (cell-adhesion molecules)
3. Recruitment of leukocytes
   1. Margination
      1. Adherence of leukocytes to cells
   2. Diapedesis
      1. Leukocytes squeezed out of cells
   3. Chemotaxis
      1. Chemicals from dead cells release substances to attract immune cells
4. Delivery of plasma proteins
   1. Immunoglobulins
   2. Complements
   3. Clotting proteins
   4. Kinins (increased CAM production, sensory receptor stimulation, removal of unwanted cells)

• Signs of inflammation
• Redness
• Increased blood flow
• Heat expelled
• Increased metabolic activity
• Swelling
• Pain
• Fluid build up
  • Acute inflammatory response
    • 8-10 days
  • Chronic inflammation
    • Longer than 2 weeks
    • Due to overuse (repetitive motion)

Fever

• Abnormal elevation of body temperature; 1 degree difference (37 to 38 degrees)
• Results from release of pyrogens
• Stages of fever:
  • Onset
    • Pyrogens target hypothalamus
    • Release prostaglandin E2
    • Hypothalamus stimulate vasoconstriction (keep heat in)
    • Muscles shiver (give up heat)
    • Temperature rises
  • Stadium
    • Elevated temp maintained
    • Metabolic rate increases
    • Promote innate and adaptive immunity
    • Liver and spleen bind zinc and iron to slow microbial growth
  • Defervescence
    • Time when temp returns to normal
    • Hypothalamus no longer stimulated
    • No pyrogen and prostaglandin E2
    • Releases heat instead (vasodilation) via sweat
• Benefits of Fever
  • Inhibits reproduction of bacteria and virus
  • Promotes interferon activity
  • Increases CAMs
  • Increases activity of adaptive immunity
  • Increases tissue repair
• Risks of high fever
  • Potentially dangerous
    • Denatured proteins
  • Possible seizures

Adaptive Immunity

• 3rd line of defense
• Specific antigen (usually foreign)
• Longer response
• Cell-mediated
  • T-lymphocytes differentiate into cytotoxic or helper-T lymphocytes
  • Cytotoxic: destroy cells through apoptosis
  • Helper-T: release molecules that regulate immune system
• Antibody-mediated
  • B-lymphocytes develop into plasma cells that produce antibodies

Antigens

• Protein or large polysaccharide molecule
• Substance that binds to a component of adaptive immunity
  • T-lymphocyte
  • antibodies
• Foreign antigen
  • Bind to immune parts
  • Differ from body molecules
• Self-antigen
  • Body’s own molecules
  • Don't bind to immune component
• Antigenic determinant
  • Binding of antibody or lymphocyte
  • Have own unique shape
• Immunogen
  • Immunogenicity can increase with:
    • Foreignness
    • Size
    • Complexity
    • Quantity
• Haptens
  • Small to be an antigen but when binded with another substance and form a complex, it can become dangerous

Lymphocytes

• B-cells
  • Make direct contact with antigen
  • BCR (B-cell receptor)
• T-cells
  • Must have antigen presented by another cell
    • Ex. dendritic cells broken down and displayed on plasma membrane
  • TCR (T-cell receptor)
    • Helper T-lymphocytes
      • CD4 protein
        • Assist cell mediated and antibody mediated immunity
        • Enhances innate immunity
    • Cytotoxic T-lymphocytes
      • CD8 protein
        • Release chemicals that destroy other cells

Antigen-Presenting Cells and MHC Molecules

• Antigen Presentation
  • All nucleated cells of the body
  • Antigen-presenting cells (APCs)
    • Immune cells that can present to cytotoxic and helper-T lymphocytes
• Attachment of antigen to MHC (major histocompatibility complex) molecules
  • Transmembrane proteins:
  • MHC Class I
    • Found on all nucleated cells
    • Found on APCs
  • MHC Class II
    • Found on APC

MHC Class I Molecules on nucleated cells

• Endogenous Pathway in Healthy Cell

1. MHC Class I molecules are continuously synthesized by the rough ER.
   1. During production, peptide fragments of the cell (self-antigens) bind with the MHC class I molecules
2. Transport vehicles are produced from the rough ER that contain MHC Class I molecules with bound self-antigen
   1. They are shipped by the endomembrane system through the golgi apparatus to plasma membrane

• Endogenous Pathway in Unhealthy Cell
  • Proteins of viral particles are digested by proteasomes into peptide fragments; peptide fragments are taken up into the rough ER

1. As MHC Class I molecules are synthesized by the rough ER, peptide fragments of the viral particle become attached to MHC class I molecules
2. Transport vesicles are produced from the rough ER that contain MHC class I molecules with other peptide fragments
   1. They are shipped by the endomembrane system through the Golgi apparatus to the plasma membrane
3. MHC Class I molecules with bound foreign antigen are displayed within the plasma membrane following fusion of the secretory vesicles with the plasma membrane

MHC Class II Molecules on APC

Exogenous Pathway

1. MHC class II molecules are synthesized by the rough ER of the APC
2. MHC class II molecules are shipped by the endomembrane system through the Golgi apparatus and form transport vesicles
3. During the process of phagocytosis and destruction of an exogenous antigen, vesicles containing digested peptide fragments called phagosomes combine with a lysosome
   1. The combined structure is a phagolysosome
4. Secretory vesicles containing MHC class II molecules merge with the phagolysosome containing the digested foreign antigen
   1. The combined structure is a secretory vesicle, where antigen MHC class II molecules bind with foreign antigen
   2. MHC class II molecules and foreign antigen are displayed within the plasma membrane

Overview of Life Events of Lymphocytes

• Formation
  • Occur in primary lymphatic structures
  • Recognize one specific antigen
• Activation
  • Secondary lymphatic structures
  • First exposure to an antigen
  • Replication and production
• Effector Response
  • Events of lymphocytes
  • T-lymphocytes:
    • migrate to site of infection
  • B-lymphocytes:
    • stay in the structures
    • Reside as plasma cells
      • Produce antibodies to go to site of infection

Formation of T-lymphocytes

• Originate in red bone marrow
• Migrate to thymus to complete maturation
  • Thymocytes
    • Contain both CD4 and CD8 proteins
    • Each have a unique TCR that needs to be tested
      • Tested for binding to MHC molecules or foreign antigens (self vs. foreign)
• Thymic selection - 98% of thymocytes get eliminated
  • Positive selection
    • Cortex of thymus
    • Ability to bind with MHC molecules
      • Binds - survives
      • Doesn’t bind - eliminated
  • Negative selection
    • Medulla of thymus
    • Ability to avoid binding self-antigens
    • Dendritic (RPC) cells and MHC molecules present self-antigen
      • No binding - survives
      • Bind - eliminated
    • Thymocytes cannot bind to self-antigens (autoimmune)
• Differentiation into helper T-lymphocyte or cytotoxic T-lymphocyte

Activation of T-lymphocytes

• Require 2 signals
  • Helper T-lymphocytes

1. First signal:
   1. CD4 binds with MHC class II molecule of APC; TCR interacts with antigen within MHC class II molecule
2. Second signal:
   1. Other receptors interact (not shown)
   2. IL-2 released from helper T-lymphocyte binds with helper T-lymphocytes to promote their proliferation and differentiation
   3. Activated helper-T lymphocytes proliferate and differentiate to form a clone of activated or memory helper T-lymphocytes.
   • Cytotoxic T-lymphocytes
3. First signal:
   1. CD8 binds with MHC class I molecule of infected cell
   2. TCR interacts with antigen within MHC class I molecule
4. Second signal:
   1. Other receptors interact
   2. IL-2 released from activated helper T-lymphocyte binds with cytotoxic T-lymphocytes to promote their proliferation and differentiation
   3. Activated cytotoxic T-lymphocyte proliferates and differentiates to form a clone of activated and memory cytotoxic T-lymphocytes

Activation of B-lymphocytes - can respond to antigens but needs to be activated first

• Require 2 signals for activation

1. First signal:
   1. Free antigen binds to BCR
   2. B-lymphocyte engulfs and presents antigen to activated helper-T lymphocyte
2. Second signal:
   1. Other receptors interact
   2. IL-4 released from activated helper T-lymphocyte stimulates B-lymphocyte
   3. Activated b-lymphocyte proliferates and differentiates to form a clone of plasma cells and memory B-lymphocytes

Effector response

• Used by lymphocytes to eliminate antigen
  • Helper T-lymphocyte
    • Synthesis and release of various cytokines (IL-2)
    • Regulate the cells of both adaptive and innate immunity
  • Cytotoxic T-lymphocyte
    • Release of cytotoxic chemicals induces apoptosis of abnormal cells
  • B-lymphocyte
    • Plasma cells release antibodies

Antibody structure

• Y-shaped
• 4 polypeptide chains
• Produced by plasma cells
• Tag pathogens but don’t destroy
• Functional areas
  • Variable regions
    • At ends of antibody arms
    • Antigen-binding site
  • Constant region
    • Same for each given class
    • Fc region
      • Determine biological function of antibody

Actions of antibodies

• Binding of antigen-binding site
  • Neutralization
    • Antibody covers active process of pathogen
  • Agglutination
    • Antigen binding site combines with antigen to crosslink - clumping
  • Precipitation
    • Antibody binds to antigen to crosslink
    • Crosslink forms a complex to be precipitated out of body fluids
• Fc region actions following antigen binding by antibody
  • Complement fixation
    • Fc region bind to complement causing activation of classical pathway
  • Opsonization
    • Fc region combines with phagocytic cells
    • Phagocytosis
  • Activation of NK cells
    • Fc region bind to NK cells
    • Apoptosis

Immunologic Memory

• Adaptive immunity
• Lag phase: all events, 3-6 days

Measure of Immunologic Memory

• Primary response
• Secondary response

Active immunity

• Need to have had activation as a result of exposure to antigen
  • Naturally
  • Artificial (immunizations)

Passive immunity

• Provided antibody
  • No memory cell production
  • From person or animal
  • Passive immunity only lasts as long as antibody

Chapter 23: Respiratory System

Respiratory System

• Air passageway
  • Alveoli to atmosphere (vice-versa)
• Site for exchange
  • Oxygen and carbon dioxide
  • Oxygen: alveoli to blood
  • Carbon dioxide: blood to alveoli
• Detection of odors
  • Olfactory receptor cells in nasal cavity
• Sound production
  • Air to vocal cords causing them to vibrate

Structural organization

• Upper respiratory tract
  • Nose, nasal cavity, pharynx, larynx
• Lower respiratory tract
  • Trachea, bronchi, bronchioles, terminal bronchioles, alveolar ducts, alveoli

Functional organization

• Conducting zone
  • Structures that transport air
  • Nose to terminal bronchioles
• Respiratory zone
  • Site of gas exchange
  • Respiratory bronchiole to alveolar duct to alveoli

Respiratory Mucosa

• Mucosa (mucosa membrane)
  • Respiratory epithelium
    • Cilia, goblet cells on basement membrane within the conducting zone
    • Gets progressively thinner
  • Lamina propria
    • Areolar CT
    • Mucous and serous glands

Upper respiratory tract

• Nose - 1st conducting structure for inhalation
• Nasal cavity - nostrils tp choanae (paired opening that lead to pharynx)
  • Nasal conchae - cause turbulence during inhalation
  • Parts
    • Nasal vestibule
      • Inside nostrils
      • Lined with skin and hairs
    • Olfactory region
      • Superior region of nasal cavity
      • Olfaction
    • Respiratory region
      • Vascular network (nosebleeds)
• Functions
  • Condition air
    • Warms
  • Humidify air
    • Moistens
  • Cleanse air
    • Mucous traps particles
    • Cilia sweeps particles

Paranasal Sinuses - connected through ducts, mucous has trapped particles

• Frontal
• Ethmoidal
• Sphenoidal
• Maxillary

Pharynx - funnel shaped passageway, air conducted through entire length

• Nasopharynx
  • Usually only air passes
  • Connect to auditory tube (ear)
• Oropharynx
  • Extend from soft palate to hyoid bone
  • Passageway for both food and air
• Laryngopharynx
  • Extend from hyoid to split of epiglottis and larynx
  • Passageway for both food and air

Larynx

• Formed and supported by a framework of 9 pieces of cartilage held by ligaments and muscle
• Between laryngopharynx and trachea
• Functions
  • Air passageway
  • Prevent materials from entering respiratory tract
  • Produces sound for speech
  • Assists in increasing pressure in the abdominal cavity
    • Vocal folds will close off Rima glottidis contracting abdominal muscle
    • Valsalva maneuver
      • Increased pressure in abdominal cavity can facilitate urination and defecation
  • Participates in both sneeze and cough reflexes
    • Release irritants from nasal cavity and lower respiratory tract
    • Sneeze: nasal cavity
    • Cough: trachea and bronchi

Larynx anatomy

• Vocal ligaments
  • Extend between thyroid and arytenoid cartilage
    • Avascular CT, mucosa covering
  • Form vocal folds
    • “True vocal cords”
    • Produce sound within air that passes through the Rima glottidis
• Vestibular ligaments
  • Extend from thyroid cartilage to arytenoid and corniculate cartilages
    • Sit superior to vocal ligaments, mucosa covering
  • Form vestibular folds
    • “False vocal cords”
    • No role in sound production
    • Protect the true vocal cords
• Characteristics of Sound
  • Range
    • Determined by length and thickness of vocal folds
    • Thicken as males get older
  • Pitch
    • Frequency of sound waves
    • Amount of tension put on by vocal folds
    • Increased tension causes more vocal fold vibration, resulting in high pitch (vice-versa)
  • Loudness
    • Depend on force of air

Lower Respiratory Tract

• Trachea
  • Tracheal cartilage
    • Support anterior and lateral walls of trachea
    • C-shaped rings
      • Hyaline cartilage
      • Ensure an open trachea
      • Connected by annular ligaments
  • Trachealis muscle
    • Connects open ends of C-shaped rings on posterior side
  • Carina
    • Split into main bronchi
    • Has sensory receptors for cough reflex
    • Internal ridge at end of trachea

Bronchial Tree

• Main bronchi
• Lobar bronchi
• Segmental bronchi
• Terminal bronchioles
  • Conducting zone
• Respiratory bronchioles
  • Respiratory zone
• Bronchi
  • Incomplete rings of hyaline cartilage - supports bronchi
  • Smooth muscle - prevents from collapsing
• Bronchioles
  • No cartilage
  • Thicker layer of smooth muscle
  • Bronchodilation (relax) and bronchoconstriction (contract)

Respiratory Zone

• Respiratory bronchioles
  • Lined with simple cuboidal epithelium
  • Alveolar ducts
    • Lined with simple squamous epithelium
    • Alveolar sacs
      • Clusters of alveoli
      • Lined with simple squamous epithelium
• Cell types of Alveolar Wall
  • Alveolar type I cells - 95%
  • Alveolar type II cells
    • Secrete pulmonary surfactant
      • Prevent alveoli from collapsing during expiration
  • Alveolar macrophage - fixed or free
• Respiratory membrane
  • Basement membranes fused
  • Diffusion of gasses takes place

Gross Anatomy of the Lung

• Hilum - indented region
  • Main bronchi
  • Pulmonary arteries
  • Pulmonary veins

Bronchopulmonary Segments

• Right lung: 10 segments
• Left lung: 8-10 segments

Circulation of the lungs

• Pulmonary circulation
  • Eliminates CO2
• Bronchial circulation
  • Descending thoracic aorta
  • Transports oxygenated blood to tissues of lungs

Lymph drainage

• Vessels, nodes within lung connective tissue, around bronchi, remove excess fluid and pathogens

Innervation of the respiratory system

• Autonomic Nervous System
  • Innervate smooth muscles, glans of respiratory structures
  • Sympathetic
    • T1-T5 segments
    • Bronchodilation
  • Parasympathetic
    • Vagus nerve innervation
    • Bronchoconstriction
  • Signal to larynx from vagus nerves

Pleural Membranes

• Visceral pleura
  • Adheres directly to lung
  • Each lung has own
  • Limits infection
• Parietal pleura
  • Line with internal wall of lateral mediastinum and superior diaphragm
• Pleural cavity
  • Serous fluid to reduce friction
• Intrapleural Pressure
  • Between membranes
  • Low pressure
• Intrapulmonary Pressure
  • Pressure within lungs
  • Greater pressure to keep lungs inflated

Respiration - exchange of gas between atmosphere and body cells

1. Pulmonary ventilation
   1. Movement of gasses between atmosphere and alveoli
2. Pulmonary gas exchange
   1. Exchange of gasses between alveoli and blood within pulmonary capillaries
3. Gas transport
   1. Transport of gasses within blood between lungs and systemic cells
4. Tissue gas exchange
   1. Exchange of gasses between systemic cells and blood

Pulmonary Ventilation

• Consists of 2 cycles
  • Inspiration
  • Expiration
• Quiet Breathing
  • Rhythmic breathing at rest
  • Diaphragm and external intercostal
  • Contracts for inspiration (flattens)
  • Relaxes during expirations (pushed-up)
• Forced Breathing
  • Vigorous breathing during activities
  • Regulated by autonomic nuclei in brainstem
  • Pull upward and outward:
    • SCM, scalenes, serratus posterior superior, pectoralis minor, erector spinae
  • Pull downward and inward (coughing)
    • Transversus thoracis
    • Serratus posterior inferior
    • Internal intercostal
    • External oblique
    • Transversus abdominis
  • These movements change thoracic volume causing changes in pressure gradients within lungs and atmosphere
  • Air moves down a pressure gradient

Volume changes in the thoracic cavity associated with breathing

• Vertical
  • Diaphragm movement
• Lateral
  • Rib cage movement
• Anterior-posterior
  • Inferior part of sternum movement

Boyle’s Gas Law

• Inverse relationship between gas pressure and volume
• Air pressure gradient exists when force per unit area is greater in one place than another

Volumes and pressure associated with breathing

• Atmospheric pressure
  • Pressure of air in environment (i.e. changes in altitude)
  • Unchanged during breathing
• Alveolar volume
  • Collective volume of alveoli
• Intrapulmonary pressure
  • Pressure in alveoli that fluctuates with breathing
  • Equal with atmospheric at end of inspiration and expiration
• Intrapleural pressure
  • Pressure within pleural cavity that fluctuates with breathing
  • Lower than intrapulmonary pressure to keep lungs inflated
• Volume changes create pressure changes
  • Air flow down its gradient
• Inspiration
  • Thoracic volume increase
  • Thoracic pressure decreases
• Expiration
  • Thoracic volume decrease
  • Thoracic pressure increase

Mechanics of Breathing

• Quiet Inspiration
  • Diaphragm and external intercostals contract to increase thoracic volume
  • Intrapleural volume increases so intrapleural pressure decreases
  • Lung volume increase so intrapulmonary pressure decreases
  • Intrapulmonary pressure is less than atmospheric pressure
  • Air goes into the lungs until pressure equalizes
• Quiet Expiration
  • Diaphragm and external intercostals relax
  • Thoracic volume decreases
  • Pleural cavity volume decreases so intrapleural pressure increases
    • Pull lungs inward
    • Alveolar volume decreases
  • Intrapulmonary pressure increases
    • Greater than atmospheric pressure
    • Air out until pressure equalizes
• Forced breathing
  • Same mechanics but includes contraction of muscles
    • Greater volume changes and pressure changes

Nervous System Control

• Respiratory center
  • Medullary respiratory center
    • Ventral respiratory group (VRG)
      • Anterior medulla
      • Synapse with lower motor neurons of skeletal muscles in spinal cord
    • Dorsal respiratory group (DRG)
      • Posterior medulla
  • Pontine respiratory center
    • Pons

Chemoreceptors

• Central chemoreceptors
  • Primary receptors involved in altering breathing
  • Monitor PCo2 and PO2 within CSF and blood
  • Medulla
  • H+ changes within CSF
    • Caused by changes of blood PCO2
• Peripheral chemoreceptors
  • Stimulated by large changes in blood PCO2
  • Carotid bodies
    • Glossopharyngeal nerve to respiratory center
  • Aortic bodies
    • Vagus nerve to respiratory center
  • Changes in concentrations of H+ and PCO2 within arterial blood
    • Produced independently of PCO2
      • Fatty acid metabolism
      • Kidney failure

Other receptors that influence respiration

• Irritant receptors
  • In air passageways that initiate the cough and sneeze reflex
  • Stimulated by dust and particulate matter
• Baroreceptors
  • Pleura and bronchioles
  • Stimulated by stretch
    • Initiate inhalation reflex
    • Prevent lungs from overstretching
    • Inhibit inspiration
• Proprioceptors
  • Stimulated by body movements
  • Increases breathing depth
• Actions of higher order brain centers
  • Hypothalamus
    • Increase breathing rate when warm
    • Decrease breathing rate when cold
    • Work through respiratory center
  • Limbic System
    • Alter breathing rate during emotional memories
    • Work through respiratory center
  • Cerebral cortex
    • Control voluntary changes in breathing rate
    • Bypasses respiratory center to stimulate lower motor neurons directly

Air Flow - amount of air that moves in and out of the lungs with each breath

• Directly related to pressure gradient
• Inversely related to resistance

Pressure gradient - difference between atmospheric pressure and alveolar pressure

• Change by altering thoracic volume

Resistance - factors that increase difficulty moving air

• Change in elasticity of chest wall and lungs
  • Decrease in elasticity will increase resistance and lessen air flow
• Change in bronchiole diameter
  • Bronchoconstriction: increase resistance, PNS stimulation, histamine release, cold exposure
  • Bronchodilation: decrease resistance, SNS stimulation, EPI stimulation
  • Occlusion: mucus and inflammation
• Collapse of alveoli
  • Increases resistance
  • Not enough pulmonary surfactant (Type II cells)

Compliance - ease with which lungs and chest wall expands

• Determined by surface tension and elasticity of chest wall and easier expansion
• Easier expansion = greater compliance

Minute Ventilation

• Amount of air moved between atmosphere and alveoli in one minute (6L/min)
• Tidal volume x respiration rate = minute volume

Anatomic dead space - conducting zone space (150mL)

Alveolar Ventilation

• Amount of air that reaches the alveoli and is available for gas exchange (4.2L/min)
  • (Tidal volume - anatomic dead space) x respiration rate = alveolar ventilation

Physiologic dead space

• Normal anatomic dead space + any loss of alveoli

Respiratory Volumes

• Four volumes
  • Tidal volume
    • Amount of air taken into or expelled out of lungs during a quiet breath
  • Inspiratory reserve volume
    • Amount of air taken into lungs during a forced inspiration, following a quiet inspiration
    • Measures lung compliance
  • Expiratory reserve volume
    • Amount of air expelled from lungs during a forced expiration, following a quiet expiration
    • Measure of lung and chest wall elasticity
  • Residual volume
    • The amount of air left (residual) in lungs following a forced expiration
• Four capacities
  • Inspiratory capacity
    • Total ability to inspire
  • Functional residual capacity
    • Amount of air normally left (residual) in lungs after you expire quietly
  • Vital capacity
    • Maximum amount of air that can be forcefully expired after a forced inspiration
  • Total lung capacity
    • Maximum amount of air the lungs can hold

Respiration: Pulmonary and Tissue Gas Exchange

• Partial pressure
  • Pressure exerted by each gas within a mixture of gasses
  • PO2
  • PCO2
• Partial pressure gradient
  • Exists when partial pressure for a gas is higher in the one region of the respiratory system than another
  • Drives gas exchange
• Henry’s law
  • At a given temperature, the solubility of a gas in a liquid depends upon the partial pressure of the air and the solubility coefficient of the gas in the liquid
  • Gasses moving within blood
• Solubility coefficient
  • Volume of gas that dissolves in a specified volume of liquid at a given temperature and pressure
• Gasses vary in solubility in water
  • O2 low solubility
    • Require a larger pressure to push them into a liquid
  • CO2 solubility 24x more

Efficiency of gas exchange at respiratory membrane

• Anatomical features of membrane
  • Large surface area
  • Thinness
  • For efficient diffusion of gasses
• Physiological adjustments
  • Ventilation-perfusion coupling: ability of bronchioles to regulate air flow and for arterioles to regulate blood flow
    • Ventilation
      • Bronchodilation increases PCO2 in air of bronchiole
      • Bronchoconstriction decreases PCO2 in air of bronchiole
    • Perfusion
      • Changes within pulmonary arteries
      • Response in decrease of PCO2 in blood or
      • Increase in increase of PO2 in blood

Gas Transport - movement of respiratory gasses within the blood between the lungs and systemic cells

• Oxygen transport
  • Solubility coefficient of oxygen
    • Low solubility so there's little dissolved in plasma (2-3%)
  • Presence of hemoglobin
    • 98& of oxygen is transported (bind with iron group of hemoglobin)
• Carbon dioxide transport
  • Dissolved within plasma
    • 7% of plasma dissolved
  • Attached to globin protein
    • 73% of carbon dioxide travels this way
  • As bicarbonate
    • Most of carbon dioxide dissolved into plasma
    • 70% of carbon dioxide

*Conversion of CO2 to HCO3 at systemic capillaries

1. CO2 movement
   1. CO2 diffuses into an erythrocyte
2. Formation of HCO3- and H+
   1. Once inside the erythrocyte, CO2 is joined to H2O to form carbonic acid by carbonic anhydrase
   2. HCO3- splits into bicarbonate and hydrogen ion

3. Chloride movement

1. HCO3- which is negatively charged exits from the erythrocyte
2. Simultaneously, chloride ion goes into the erythrocyte; this exchange is called the chloride shift

*Conversion of HCO3- to CO2 at pulmonary capillaries

1. Chloride Movement
   1. HCO3- moves into the erythrocyte as Cl- moves out to balance it
2. Formation of CO2 and H2O
3. HCO3- recombines with H+ to form H2CO3-, which dissociates into CO2 and H20
4. CO2 movement
   1. CO2 diffuses out of the erythrocyte into the plasma
   2. CO2 then diffuses into an alveolus

Hemoglobin transports

• O2
  • Oxygen hemoglobin saturation increase as PO2 increases
  • This is called the cooperative binding effect because oxygen easily binds to hemoglobin
• CO2
• H+
  • Pulmonary capillaries: 98% saturation at full PO2

Variables that influence hemoglobin binding and release of O2

• Pulmonary Gas Exchange
  • Release CO2 and H+
    • Cause shape change of hemoglobin to bind oxygen to iron
• Tissue Gas Exchange
  • CO2 binding to hemoglobin
    • Shape change causes a decreased affinity for oxygen
    • Making hemoglobin easily release oxygen
  • H+ binding to hemoglobin (Bohr Effect)
    • As mentioned above.
  • Temperature
    • Elevated temperatures diminish hemoglobins hold on oxygen
    • High metabolism also plays a role
  • Presence of 2,3-BPG
    • Stimulated by TH, GH, and testosterone
    • A molecule within erythrocytes
    • When binded with hemoglobin, additional oxygen is released

Breathing and homeostasis

• Changes in breathing rate help maintain homeostasis for pH and respiratory gasses
• Hyperventilation
  • CO2 + H20 ← H2CO3 ← H+ + HCO3- (equation is driven to left)
  • Breathing rate is above body’s demand
  • Caused by anxiety, high altitude
  • Result in faint, dizziness, numbness, tingling, cramps
  • PO2 levels rise and PCO2 levels fall in air within alveoli causing increased pressure gradients
  • No additional oxygen in blood because of 98% saturation of hemoglobin
  • Additional amounts of carbon dioxide to alveoli
  • Low blood carbon dioxide levels cause vasoconstriction
  • Decreased oxygen in the brain
  • Decreased H+ in blood (shift left), causing respiratory alkalosis - basic
• Hypoventilation
  • CO2 + H20 → H2CO3 → H+ + HCO3-
  • Slow and shallow breathing
  • Caused by airway obstruction, brainstem injury, pneumonia, etc.
  • Result in lethargy, headaches, blue skin
  • Oxygen levels decrease and carbon dioxide levels increase within alveoli creating a smaller pressure gradient
  • Blood PO2 decrease in tissues
  • Low O2 delivery to tissues causing increased H+ concentration
  • This ultimately results in respiratory acidosis - acidic

Breathing and exercise

• Depth increases
• Rate stays the same
• PO2 and PCO2 in blood stay the same
  • Increased cellular respiration
  • Compensated because of deep breathing
  • Increased cardiac output
  • Increased blood flow
  • Respiratory center stimulated

Chapter 24: Urinary System

Components of Urinary System and Functions

• Kidney
  • Filter blood
  • Remove wastes
  • Produce urine
• Bladder
  • Store urine
• Urethra
  • Eliminate urine
• Other functions of the kidneys
  • Elimination of microbic and biologically active waste (i.e. drugs and hormones)
  • Regulate ion levels (including acid-base)
    • Na+, K+, Ca2+, phosphate
  • Regulate blood pressure
    • Fluid excretion
    • Renin-angiotensin system
  • Formation of calcitriol
    • Enzyme that increases calcium absorption in the small intestine
  • EPO production during low blood oxygen levels
    • Stimulates erythropoiesis
  • Gluconeogenesis
    • Prolonged fasting
    • Production of glucose
• Support of the Kidneys
  • Fibrous capsule
    • Adheres directly to kidney
    • Dense irregular connective tissue
    • Helps maintain shape and protect from trauma and pathogens
  • Perinephric fat
    • Extend to fibrous capsule
    • Adipose connective tissue
    • Cushions and supports
  • Renal fascia
    • Extend to perinephric fact
    • Adipose connective tissue
    • Anchors kidney to surrounding structures
  • Paranephric fat
    • Outermost layer
    • Adipose connective tissue
    • Cushioning and support
• Two regions of functional tissue
  • Renal cortex
    • Renal columns have extensions of cortex to the medulla
  • Renal medulla
    • Renal pyramids
  • Corticomedullary junction
    • Where renal pyramid meets cortex
  • Renal sinus
    • Urine drainage area
    • Minor and major calyx
    • Renal pelvis
• Functional anatomy of the kidney
  • Nephron
    • Renal corpuscle
      • Glomerulus
        • Contain glomerular capillaries
      • Glomerular capsule
        • Internal visceral layer that overlies capillaries
    • Renal tubule
• Types of Nephrons
  • Cortical nephrons
    • Renal corpuscles near renal cortex
    • Short nephron loops
    • 85% of nephrons
  • Juxtamedullary nephrons
    • Loops that extend to the medulla
    • Helps establish salt concentration gradient within interstitial space
    • 15% of nephrons
• Renal Tubule
  • Proximal Convoluted Tubule (PCT)
    • Simple cuboidal epithelium
    • Long microvilli to increase surface area and reabsorption capacity
  • Nephron Loop (loop of Henle)
    • Descending limb
    • Ascending limb
  • Distal Convoluted Tubule (DCT)
    • Simple cuboidal epithelium
    • Short sparse microvilli
    • Extend to collecting duct
  • Collecting Tubules
    • Tall columnar epithelium that drain to collecting duct
  • Collecting Ducts
    • Cuboidal epithelium that empty into papillary ducts within renal papilla
  • Specialized epithelial cells
    • Principal cells: receptors that bind to aldosterone and ADH
    • Intercalated cells: regulate pH of urine and blood
      • Type A: eliminate acids
      • Type B eliminate bases
• Juxtaglomerular (JG) apparatus
  • Function to regulate filtrate formation and systemic blood pressure
  • Components
    • Granular cells
      • Modified smooth muscle cells located in afferent arteriole
      • Contract when stimulated by stretch or SNS stimulation
      • Synthesize, store, and release renin
    • Macula densa
      • Modified epithelial cells of DCT
      • Detect NaCL concentration within DCT
      • Signal to granular cells to release renin through paracrine stimulation
    • Extraglomerular mesangial cells
      • Communicate with granular cells and macula densa
• Blood Flow Through the Kidney
  • Delivered by renal artery - L/min
  • Blood moves through two capillary beds
    • Glomerular capillaries
    • Peritubular capillaries (intertwine thru PCT and DCT) or vasa recta (intertwine nephron loop)
  • Drains into network of veins then renal vein
• Filtrate, Tubular Fluid, and Urine Flow
  • Filtrate - collects in capsular space
  • Tubular fluid - flows through PCT to nephron loop to DCT, to collecting tubules, to collecting ducts, to papillary duct
  • Urine - from papillary duct to minor calyx to major calyx to renal pelvis to ureter to urinary bladder to urethra to outside body

*Urine Formation*

• Glomerular filtration
  • Separation of water and dissolved solutes from blood plasma
  • Moved by a pressure gradient
  • The movement of substances from the blood within the glomerulus into the capsular space
• Tubular reabsorption*
  • Movement of components within tubular fluid back into blood
  • Using diffusion, osmosis, active transport
  • Components such as solutes and water
  • The movement of substances from the tubular fluid back into the blood
• Tubular secretion*
  • Movement of solutes from blood into tubular fluid
  • Usually active transport
  • The movement of substances from the blood into the tubular fluid

Glomerular Filtration

• Filtration membrane
  • Thin, porous, and negatively charged
  • Glomerular endothelium
    • Fenestrated to allow plasma and dissolved substances to pass and restrict large structures like formed elements
  • Basement membrane
    • Porous to block large proteins
  • Visceral layer of glomerular capsule
    • Composed of podocytes
      • Processes around capillaries to support them (like astrocytes)
      • Filtration slits: restrict passage of small proteins

Formation of filtrate and its composition

• Freely filtered
  • Water, glucose, amino acids, ions, some hormones, water-soluble vitamins, ketones
• Not filtered
  • Formed elements and large proteins
• Limited filtration
  • Intermediate sized proteins and negative charges

Pressures associated with Glomerular Filtration

• Glomerular hydrostatic pressure - blood pressure in glomerulus
  • Driving force for filtration
    • Push water and dissolved solutes in capsular space
  • Larger diameter of afferent arteriole
  • Smaller diameter of efferent arteriole
    • These differences create a higher pressure
• Blood colloid osmotic pressure
  • Osmotic pressure exerted by dissolved solutes
  • Opposes filtration to push fluid into glomerulus
• Hydrostatic pressure in the capsule
  • Pressure in glomerular capsule due to filtrate
  • Opposes filtration to impede movement of additional fluid
• Net filtration pressure
  • GHP (BCOP x HPC) = NFP
  • Osmotic pressure>>Hydrostatic pressure = no filtration
  • Osmotic pressure<<Hydrostatic pressure = filtration

Variables influenced by net filtration pressure

• Glomerular filtration rate (GFR)
  • Rate at which the volume of filtrate is formed
  • Influenced directly by net filtration pressure
• Increased NFP
  • Increases in GFR
  • Increases solutes and water remaining in filtrate
  • Increases substances in urine
  • Decreases filtrate reabsorption

Regulation of Glomerular Filtration Rate

• Tightly regulated
• Control urine production
• Based on physiological condition
• GFR influenced by
  • Changing luminal diameter or afferent arteriole
  • Influenced by…
  • Altering surface area of filtration membrane
• Intrinsic control (within kidney)
  • Renal autoregulation
• Kidneys maintain control of a constant blood pressure and GFR
  • • Myogenic response
    • Tubuloglomerular feedback mechanism
      • Backup to myogenic response
• Extrinsic control (external to kidney)
  • Involve nervous system regulation (decrease GFR) and hormonal regulation (increase GFR)

Myogenic Response

• Contraction or relaxation of smooth muscle in response to stretch in the afferent arteriole
• Decrease in systemic blood pressure
  • Less stretch of smooth muscle
  • Vasodilation of afferent arteriole
  • Blood moves along the glomerulus
  • This offsets the blood pressure
  • GFR is normal
• Increase in systemic blood pressure
  • Stretch is present causing vasoconstriction
  • Less blood travels in glomerulus to offset an increase in systemic blood pressure

Tubuloglomerular feedback mechanism

• Backup to myogenic response to increased blood pressure
  • Increased glomerular blood pressure
  • Macula densa cells detect increased NaCL concentration in tubular fluid
  • Vasoconstriction at afferent arteriole
  • Decreased blood flow
  • Maintain GFR
• Limitation:
  • Renal autoregulation can be maintained as long as systemic blood pressure is normal (80-180)
  • <80 - filtration and elimination of waste stops causing toxicity
  • >180 - increased urine produced leading to low fluid volume in the body

Extrinsic Controls: neural and hormonal control

• Decreasing GFR through sympathetic stimulation
  • Stimulus: emergency or exercise
  • Granular cells of JG release renin
  • Increase in angiotensin II production
  • Contraction of mesangial cells
  • Result
    • Decreased filtration surface area
    • Decreased blood flow
    • Vasoconstriction of afferent arteriole
  • Net effect
    • GFR decreased and filtrate decreased
    • Fluid retained in blood which maintains blood volume
• Increasing GFR through atrial natriuretic peptide (ANP, released from cardiac muscle)
  • Stimulus: increased in blood volume or blood pressure
  • This stretches atrial wall releasing ANP
  • Renin is released from granular cells of JG apparatus inhibited
  • Afferent arteriole is vasodilated
  • Result
    • Vasodilation of afferent arteriole increases blood flow into the glomerulus
    • Relax mesangial cells causing vasodilation increases filtration surface area
  • Net
    • GFR increased and filtrate increased
    • More fluid eliminated in urine which decreases blood volume

Overview of Transport Processes

• Peritubular capillary
  • Low hydrostatic pressure; high colloid pressure
  • Facilitate reabsorption through bulk flow
  • Most within PCT
  • Microvilli to aid absorption
• Paracellular transport
  • Between epithelial cells
• Transcellular transport
  • Through epithelial cells
  • Luminal membrane
  • Basolateral membrane
• Tubular reabsorption
  • Substances move from tubule into blood
• Tubular secretion
  • Substances move from blood into tubule

Transport maximum

• Maximum amount of a substance that can be reabsorbed or secreted across the tubular epithelium in a given period of time
  • Rate of movement
  • Dependent on # of transport proteins

Renal threshold

• Maximum plasma concentration of a substance that can be carried in blood before appearing in urine
  • If exceeded, any other substance is excreted in urine

Substances reabsorbed completely

• Nutrients: glucose, amino acids, lactate
  • Glucose reabsorption
    • Located mostly in PCT
    • Luminal membrane: Glucose is transported up its concentration gradient by secondary active transport using Na/glucose symporters
      • 0% of glucose remains in tubular fluid
    • Basolateral membrane: Glucose diffuses down its concentration gradient by facilitated diffusion using glucose uniporters
      • 100% of glucose reabsorbed into blood
• Proteins: transported versus reabsorbed
  • Digested by lysosomes or peptidases into amino acids
    • Protein is moved into tubular cell by endocytosis
      • 0% of protein remains in tubular fluid
    • Amino acids are released by exocytosis
      • 100% of amino acids reclaimed into blood for protein turnover
  • Amino acid (not the protein) moved back into blood

Substances with Regulated Reabsorption

• Sodium reabsorption
• Low in tubular cell
• High in tubular lumen
• High within interstitial fluid
  • Tubules
    • 65% of sodium reabsorbed in PCT
    • 5% of sodium reabsorbed in DCT
    • 25% of sodium reabsorbed in nephron loop
    • Regulated percent of sodium reabsorbed by principal cells of collecting tubule and collecting duct
  • Sodium transport in PCT
    • Luminal membrane: sodium moves down its concentration gradient by facilitated diffusion
      • 35% of sodium remains in tubular fluid
    • Basolateral membrane: sodium is moved up its concentration gradient by active transport
      • 65% of sodium reabsorbed into the blood
    • Sodium in peritubular and vasa recta capillaries
  • Sodium transport in collecting tubule and collecting duct
    • Aldosterone increases both the number of sodium channels and Na/K pumps, resulting in an increase in sodium reabsorption
  • DCT: collecting tubules and collecting ducts
    • Regulated by aldosterone and ANP
    • Aldosterone
      • Enter principal cells bind to receptors and stimulate sodium channels and Na/K pumps
      • Increases sodium and water (follows Na) reabsorption
    • ANP
      • Inhibit sodium reabsorption in PCT and collecting tubules
      • Inhibit aldosterone (more sodium and water excreted in urine)

Water reabsorption

• Paracellular transport
• Transcellular transport
  • Aquaporins (water transport proteins)
• PCT - 65% of water reabsorbed
  • Obligatory water reabsorption
    • Dependent of sodium
    • When water follows sodium via osmosis
    • What happens to sodium, happens to water
• Nephron loop
• DCt, collecting tubules and ducts
  • Controlled by aldosterone and ADH (more aquaporins)
    • Facultative water reabsorption
      • Independent of sodium (just water)

Potassium

• Both reabsorbed and secreted
  • 60-80% of potassium reabsorbed in PCT
  • 10-20% of potassium reabsorbed in nephron loop (thick segment)
  • Regulated potassium reabsorption and secretion in collecting tubules
  • Type A intercalated cells reabsorb potassium continuously
  • Principal cells vary potassium secreted, depending upon aldosterone levels

Calcium and Phosphate

• Mainly stored as calcium phosphate in bone
  • PTH inhibits reabsorption of phosphate in PCT
  • PTH stimulates reabsorption of calcium in DCT
  • Results in increased phosphate lost in urine
    • Less phosphate for that calcium to be bound to in order for calcium to be stored in bone
    • Leads to increased blood calcium levels

Bicarbonate and hydrogen ions

• Bicarbonate move freely across filtration membrane (80-90% reclaimed in PCT, if not blood becomes acidic) - (10-20% taken up in thick segment of ascending limb
• Acidic blood
  • Type A intercalated cell secrete hydrogen ions within the filtrate (to urine)
  • This synthesizes bicarbonate
  • Bicarbonate is reabsorbed into the blood
  • Blood pH rises and urine pH decreases
• Alkaline blood
  • Low hydrogen ions activate type A intercalated cells
  • This synthesizes bicarbonate
  • Bicarbonate secretion within filtrate
  • Urine pH rises; blood pH decreases

Substances eliminated as waste products

• Nitrogenous waste
  • Metabolic waste containing nitrogen
  • Urea
    • From protein destruction in liver
    • Reabsorbed and secreted
  • Uric acid
    • From nucleic acid breakdown in liver
    • Reabsorbed and secreted
  • Creatinine
    • Creatine metabolism in skeletal muscle
    • Secreted only
• Drugs and bioactive agents
  • Antibiotic, bilirubin, hCG

Concentration Gradient

• Established by various solutes
• Around nephron loop and interstitial fluid
• Exert osmotic pressure on water to interstitial fluid when ADH is present
• Nephron loop
  • Countercurrent multiplier - positive feedback; establish concentration gradient involving nephron loop
    • Descending limb
      • Permeable to water
      • Impermeable to salt
    • Ascending limb
      • Impermeable to water
      • Permeable to salt
    • Salt is retained in tubular fluid until there's too much then it leaves to maintain balance
• Vasa recta
  • Countercurrent exchange
    • Maintains the gradient
    • Descending limb
      • Water out vasa recta
      • Salt into vasa recta
    • Salt concentration rises within vasa recta
    • Ascending limb
      • Water into vasa recta
      • Salt out vasa recta

Urine Characteristics

• Composition
  • Mostly water (95%)
  • Solutes (5%)
    • Salts
    • Nitrogenous wastes
    • Hormones
    • Drugs
    • Ketone bodies
• Volume
  • 1-2L/day (need at least 0.5 L/day)
• pH between 4.5 - 8.0 (normal - 6.0)
  • Protein and wheat - low pH
  • Fruits and vegetables - high pH
• Specific gravity slightly higher than water due to solutes
• Color and turbidity
  • Clear to dark yellow
• Urinoid (smell)

Urinary Tract

• Ureters
  • Mucosa
  • Muscularis
  • Adventitia
• Innervated by autonomic nervous system
  • Sympathetic
    • Extend from T11 to L2 segments
  • Parasympathetic
    • Extend from vagus and pelvic splanchnic nerves

Urinary Bladder

• Mucosa
  • Supported by lamina propria
  • Has folds for greater surface area
• Submucosa
  • Dense irregular CT
• Muscularis
  • Contains detrusor muscle
  • Involuntary urethral sphincter
• Adventitia
• Trigone - triangular area
  • Remains immoble
  • Funnel from bladder to urethra
  • Common for infections

Urethra

• Internal urethral sphincter
  • Smooth muscle that surrounds neck of bladder
  • Involuntary - ANS stimulation
• External urethral sphincter
  • Formed by skeletal muscle from pelvic diaphragm
  • Voluntary - somatic stimulation
• Female urethra
  • Urine is taken from the bladder to urethra and out of the body
  • Open to external urethral orifice within perineum
• Male urethra - both urine and semen
  • Prostatic urethra
    • Dilatable portion
  • Membranous urethra
    • Least dilatable, extend through urogenital diaphragm
  • Spongy urethra
    • Largest; encased in erectile tissue that extends to external urethral orifice

Micturition - expulsion of urine from bladder

• Associated with two reflexes
• Storage Reflex
  • Continuous SNS stimulation
  • Relaxation of detrusor muscle to accommodate urine
  • Contraction of internal urethral sphincter
  • Pudendal nerve stimulate external urethral sphincter (contract)
• Micturition reflex

1. : a.) detrusor muscle stretched b.) internal urethral sphincter contracted c.) external urethral sphincter contracted
2. Baroreceptors detect distended sensation within the bladder and signal to the micturition center in the pons
3. Signal travels through pelvic splanchnic nerves via PNS stimulation
4. : a.) detrusor muscle contracts b.) internal urethral sphincter relaxed c.) external urethral sphincter relaxed
5. : a.) urination occurs in non-potty trained people b.) signal from cerebral cortex via pudendal nerve

• Empty bladder: detrusor muscle relaxes, internal urethral sphincter contracts
• Holding in: detrusor muscle relaxes until the maximum amount of 500-600mL is reached, then forced urination occurs

Chapter 26: Digestive System

Digestive System Functions

• Ingestion of food into the oral cavity
• Motility that includes involuntary and voluntary muscle contractions that mix and move food
• Secretions such as bile and enzymes to facilitate digestion
• Digestion
  • Mechanical
    • Physically breaking down food, but not changing its chemical composition
  • Chemical
    • Enzymes that change the chemical structure by breaking down bonds
• Absorption
  • Transport digested molecules from the lumen to blood
• Elimination
  • Expulsion of unwanted and digested proteins

GI Tract Organs

• Oral Cavity
• Pharynx
• Esophagus
• Stomach
• Small Intestine
• Large Intestine
• Anus

Accessory Digestive Organs

• Teeth
• Tongue
• Salivary Glands
• Liver
• Gallbladder
• Pancreas

Gastrointestinal Tract Wall

• Four concentric layers
  • Mucosa
    • Epithelium - simple columnar epi. (absorption and secretion), except for esophagus (non-keratinized stratified squamous epi.)
    • Lamina propria
  • Submucosa - vessels, nerves, lymph vessels, contain submucosal nerve plexus to innervate smooth muscle and glands
    • Areolar and dense irregular CT
  • Muscularis - involved in mixing function and propulsion (peristalsis)
    • Inner circular layer - constricts the tube
    • Outer longitudinal layer - shortens the tube, contain myenteric nerve plexus to control contractions
  • Adventitia/Serosa
    • Adventitia - organs out of peritoneal cavity
    • Serosa - organs within peritoneal cavity

Regulation of Digestive System

• Receptors
  • Mechanoreceptors - i.e. baroreceptors
  • Chemoreceptors
• Nervous
  • Autonomic nervous system - long reflexes (facial, glossopharyngeal, vagus)
    • Sensory input into CNS and autonomic motor output
    • Parasympathetic - promotes GI tract activity
    • Sympathetic - opposes GI tract activity
  • Enteric nervous system - short reflexes
    • Sensory and motor information relayed within submucosal and myenteric plexus
    • Innervate smooth muscle and glands of GI tract reflexes for mixing and propulsion
• Hormonal
  • Gastrin - stomach, secretion of HCl
  • Secretin - small intestine, HCO3- secretion from pancreas
  • CCK - digestion of fats, CHO, proteins

Serous Membranes

• Parietal peritoneum
  • Line inner abdominal wall
• Visceral peritoneum
  • Cover organ surface
• Peritoneal cavity
  • Between parietal and visceral
  • Contain serous fluid
• Intraperitoneal organs
  • Have viscera completely surrounding them
  • Stomach, most of S.I., parts of colon
  • serosa layer
• Retroperitoneal organs
  • Only anterolateral portion is covered by parietal peritoneum
  • Organs that live against posterior abdominal wall
  • Duodenum, pancreas, ascending and descending colon, rectum
  • Adventitia layer
• Mesentery - double layer of peritoneum that supports and suspends organs
  • Greater omentum
  • Lesser omentum

Upper GI Tract and Associated Accessory Organs

• Oral cavity
  • Mainly mechanical and chemical digestion
  • Chewing motion
  • Salivary amylase from saliva secreted in response to entry of food
  • Formation of a bolus (from food and saliva)
• Salivary glands
  • Secrete saliva that contains salivary amylase enzyme
  • I.e. parotid, submandibular, sublingual
• Pharynx
  • Prevents bolus from entering respiratory tract
• Esophagus
  • Bolus is transported to stomach via peristalsis
• Stomach
  • Bolus gets mixed with different secretions
  • Formation of chyme

Salivary Glands

• Intrinsic salivary glands
  • unicellular, release secretions independent of food
  • Release lingual lipase
• Extrinsic salivary glands - most saliva production
  • Parotid salivary gland
    • Mostly serous cells
  • Submandibular salivary gland
    • Mix of serous and mucous cells
  • Sublingual salivary gland
    • Mostly mucous cells
• Serous cells
  • Salivary amylase
  • Electrolytes
• Mucous cells
  • Mucin

Function of saliva

• Moistens food
• Initiates chemical breakdown
• Medium for taste
• Cleanses oral cavity
• Inhibits bacterial growth

Mechanical digestion

• Mastication - controlled by nuclei in medulla and pons
  • Increases surface area
  • Promotes salivation
• Teeth
  • Exposed crown and constricted neck
  • Bound to alveolar processes by periodontal ligament

Pharynx

• Saw in respiratory

Esophagus - tube passageway that is normally collapsed

• Superior esophageal sphincter
  • Contracted ring of skeletal muscle
  • Closed during inhalation
• Inferior esophageal sphincter
  • Circular ring of skeletal muscle to stomach
  • Helped by diaphragm to avoid reflux

Mucosa - innermost layer, non-keratinized stratified squamous epithelium

Submucosa - thick, elastic fibers

Muscularis - smooth and skeletal muscle

• Upper ⅓ of skeletal muscle to move quickly out of pharynx
• Middle ⅓ of smooth and skeletal muscle
• Lower ⅓ of smooth muscle only

Adventitia - outer

Swallowing Process

• Voluntary phase
  • Occurs after ingestion
  • Controlled by cerebral cortex
  • Bolus of food is pushed by tongue against hard palate and then moves toward oropharynx
• Pharyngeal phase
  • Involuntary reflex
    • Bolus activates receptors to which the swallowing center in the medulla gets activated
  • As bolus moves into oropharynx, the soft pate and uvula elevate and close off the nasopharynx, and the larynx elevates so the epiglottis closes over laryngeal inlet
  • This mechanism protects the respiratory passageway
• Esophageal phase
  • Involuntary
  • Soft palate, uvula, and epiglottis return to pre swallowing position
  • Superior esophageal sphincter closes
  • Bolus passes through esophagus and enters the stomach
  • Inferior esophageal sphincter opens
  • Peristaltic contractions of esophageal muscle push bolus toward stomach

Stomach

• Chemical digestion
• Release intrinsic factor
  • B12 absorption
• Four regions (superior to inferior)
  • Cardia
  • Fundus
  • Body
  • Pylorus
• Gastric pits
  • Depression within epithelium
• Gastric glands
  • Extend to mucosa
• Gastric secretions
• Muscularis
  • 3 layers - oblique, circular, longitudinal

Gastric Secretions

• Mucous cells
  • Surface mucous
  • Mucous neck
• Chief cells
  • Pepsinogen
  • Gastric lipase
• G cells (enteroendocrine)
  • Gastrin
• Parietal cells
  • Intrinsic factor
    • Required for B12 absorption
  • Hydrochloric acid (HCl-)
    • Converts pepsinogen to pepsin
    • Kills microorganisms
    • Breaks down cell walls and animal connective tissue
    • Denatures proteins

Stomach Motility

• Gastric mixing

1. Contractions of smooth muscle in stomach wall mix bolus with gastric secretions to form chyme
2. Peristaltic wave results in pressure gradient that moves stomach contents toward the pylorus region

• Gastric emptying

1. Pressure gradient increases force in pylorus against pyloric sphincter
2. Pyloric sphincter opens, and a small volume of chyme enters the duodenum
3. Pyloric sphincter closes, and retropulsion occurs

Regulation of Digestive Processes in Stomach - contain pacemaker cells

• Cephalic phase
  • Initiated by thought, smell, sight, or taste of food
  • No hormones secreted
  • Cephalic reflex

1. Receptors: special sense receptors
2. Sensory input: increased nerve signals relayed from cerebral cortex and hypothalamus to medulla oblongata
3. Medulla oblongata integrates input from higher brain centers
4. Motor output: increased nerve signals relayed along vagus nerve to stomach
5. Effector: stomach stimulated to increase both its force of contraction and release of secretions

• Gastric phase
  • Initiated by presence of food in stomach
  • Hormone secreted: gastrin (increases force of stomach contractions and release of secretions, contracts pyloric sphincter)
  • Gastric reflex

1. Receptors: baroreceptors in stomach wall detect stretch; chemoreceptors detect protein or high pH in stomach contents
2. Sensory input: increased nerve signals relayed to medulla oblongata
3. Medulla oblongata integrates sensory input
4. Motor output: increased nerve signals relayed along vagus nerve to stomach
5. Effector: stomach stimulated to increase both its force of contraction and release of secretions

• Intestinal phase
  • Initiated by presence of acidic chyme in duodenum
  • Hormones secreted: CCK (decreases the force of contraction in the stomach), secretin (inhibits releases of stomach secretions)
  • Intestinal reflex - opposes cephalic and gastric reflexes - neural

1. Receptors: chemoreceptors in intestinal wall detect acidic chyme or low pH in duodenum contents
2. Sensory input: decreased nerve signals relayed to medulla oblongata
3. Medulla oblongata integrates sensory input
4. Motor output: decreased nerve signals relayed along vagus nerve to stomach
5. Effector: stomach inhibited to decrease both its force of contraction and release of secretions

• CCK and secretin released
  • Inhibit gastrin secretion and thus motility and secretion in stomach
  • Promote activity in small intestine

Lower GI Tract

• Small intestine
  • Duodenum
  • Jejunum
  • Ileum
• Large intestine
• Accessory organs
  • Liver
  • Gallbladder
  • Pancreas

Small Intestine

• Structures that increase surface area
  • Circular folds
    • Folds to increase surface area
    • Slows chyme movement
    • Numerous in duodenum, jejunum
  • Villi
    • Increased surface area for absorption
    • Large and numerous in jejunum
    • Capillary network
    • Lacteals
  • Microvilli
    • On apical surface of epithelium
• Secretions
  • Goblet cells
    • Release mucin to lubricate S.I.
    • Increases throughout S.I. tract
  • Unicellular gland cells
    • Secrete lysosomes and other microbial agents
  • Enteroendocrine cells
    • Release CCK and mucin

Motility of the Small Intestine

• Segmentation
  • Mixing chyme with secretions from accessory glands, and intestinal juice
• Peristalsis - initiated by motilin
  • Migrating motility complex
    • Propulsion along the tract
• Moving chyme from small intestine to large intestine
  • Gastroileal reflex
    • Initiated by gastric phase
    • Ileum contracts = ileocecal valve relaxes

Liver

• Functions
  • Formation of bile (main function)
    • Hepatocytes - produce bile
      • Bile salts and lecithin to help digest lipids
  • Formation of plasma proteins
  • Removal of bilirubin
  • Synthesizes cholesterol
  • Stores glycogen

Gallbladder and ducts

1. Left and right hepatic ducts merge to form a common hepatic duct
2. Common hepatic and cystic ducts merge to form a common bile duct
3. Main pancreatic duct merges with common bile duct at the hepatopancreatic ampulla, which extends into the duodenum
4. Bile and pancreatic juices enter duodenum at the major duodenal papilla

Pancreas

• Endocrine cells
  • Insulin and glucagon
• Exocrine cells
  • Acinar cells and duct cells release pancreatic juice that is also transported out of the cell by the duct cells
  • Functions to neutralize acidic chyme in small intestine
• Pancreatic juice - water, alkaline fluid (HCO3-)
  • Pancreatic amylase - starch
  • Pancreatic lipase - triglycerides
  • Inactive proteases - when activated it will digest proteins
  • Nucleases - nucleic acids

Regulation of Accessory Structures

• Cholecystokinin (CCK)
  • Stimulates the gallbladder to contracts and release bile
  • Stimulates pancreas to release pancreatic juice
  • Relaxes smooth muscle in hepatic pancreatic ampulla so bile gets released into the duodenum
  • Released from S.I. in response to free fatty acids in chyme
  • Inhibits stomach motility and release of gastric secretions
• Secretin
  • Release alkaline solutions from liver and pancreatic ducts to neutralize chyme
  • Released from S.I. in response to increased chyme acidity
  • Inhibits stomach motility and release of gastric secretions

Large Intestine

• Functions
  • Water and electrolyte absorption
  • Solidifies and compacts undigested materials
  • Form and store feces until defecation
• Cecum
  • Extend from ileocecal valve
  • Where chyme enters from ileum of small intestine
  • Vermiform appendix
• Colon
  • Ascending
  • Transverse
  • Descending
  • Sigmoid
• Rectum
  • Muscular tube
  • Expands to store feces until defecation
  • Rectal valves - thick transverse folds that keep feces in during gas movement
• Anal canal
  • Stratified squamous epithelium
  • Internal anal sphincter = involuntary smooth muscle
  • External anal sphincter = voluntary skeletal muscle
• Intestinal glands
• Goblet cells
  • Mucin to lubricate passageway
• Lymphatic nodules
  • Lots within lamina propria
• Normal bacterial flora (GI flora)
  • Digestion of protein, CHO, lipids
  • Turns into CO2, vitamins B and K and absorbed in the blood
• Feces
  • Bacteria, water, salts, epithelia, undigested material

Motility and Regulation in the Large Intestine

• Motility
  • Peristalsis (weak)
  • Haustral churning
    • As the haustrum (folds in LI) fills, it will stretch and move on to the next haustrum
  • Mass movements
    • Powerful contractions that involve teniae coli which propels fecal matter to the rectum
    • 2-3x a day, follows a meal
• Reflexes
  • Gastrocolic reflex
    • By stomach distension causing mass movement in L.I.
  • Defecation reflex
    • Initiated by filling of rectum

1. Rectum contents stimulate baroreceptors in rectal wall
2. Sensory input initiated by baroreceptors in rectum is relayed to the spinal cord
3. Motor output along parasympathetic axons is altered
4. Increased motor output to smooth muscle of rectum; rectum contracts, squeezing the contents. Decreased motor output to the internal anal sphincter causes sphincter relaxation.
5. The conscious decision to defecate is controlled by the cerebral cortex. External anal sphincter relaxes and Valsalva maneuver is initiated, eliminating the feces

Nutrient Digestion

• Carbohydrates
  • Breakdown starch into glucose
  • Disaccharides into monosaccharides
• Oral cavity
  • Salivary amylase - break bonds of glucose molecules inactivated in the stomach
• Small intestine
  • Pancreatic amylase - continue starch digestion
    • Produced by pancreas
    • Secreted into duodenum
      • Ex. partially digested starch is digested by pancreatic amylase into oligosaccharides
        • Dextrinase, glucoamylase, maltase digests it further into individual glucose molecules
  • Brush border enzymes - complete starch digestion
    • Starch is broken down to individual glucose molecules
    • Digests disaccharides
      • Ex. lactase digests lactose into glucose and galactose

Small Intestine

• Absorption
  • Monosaccharides are absorbed through the intestinal epithelium into the bloodstream
  • Travels to liver were fructose and galactose is converted to glucose
• Glucose
  • Used by cells
  • Converted to glycogen
  • Converted to fat
• Cellulose
  • not digestible

Protein Digestion

• Stomach
  • Pepsin
  • HCl (denatures) and activates pepsinogen to pepsin
• Small intestine
  • Pepsin inhibited
  • Trypsinogen is activated by enteropeptidase to trypsin
  • Free amino acids absorbed by the intestinal epithelium
• Pancreas
  • Trypsin (trypsinogen) and chymotrypsin (chymotrypsinogen)
    • Break bonds between specific amino acids into smaller strands
  • Carboxypeptidase (procarboxypeptidase)
    • Break bonds between amino acids on carboxyl end (one at a time) and remain protein
• Brush border enzymes
  • Dipeptidases
    • Break final bond between a dipeptide
  • Aminopeptidase
    • Generate free amino acids from amine end of peptide

1. Proteolytic enzymes are released from pancreas
2. Enteropeptidase activates trypsinogen to trypsin; trypsin then activates other proteolytic enzymes
3. Activated pancreatic proteolytic enzymes break proteins into peptides and amino acids
4. Brush border peptidases break peptides into single amino acids to be absorbed through epithelial cell into blood

Absorption

• Across S.I. epithelial lining

Lipids - triglycerides (requires enzymes) and cholesterol

• Digestion
  • Stomach
    • Lingual lipase
      • Released from oral cavity and activated at the stomach
    • Gastric lipase
      • The two digest 30% of triglycerides into a diglyceride and a fatty acid
  • Small intestine
    • Pancreatic lipase
      • Break into monoglyceride and 2 fatty acids
    • Bile salts
      • Cause emulsification and breaks large lipid droplets into smaller ones (amphipathic)
      • Micelles
        • Ring around bile salt that allows for lipase to get into lipid droplets
    • Transport: lipid into epithelial cells (bile salts remain in small intestine)
      • Epithelial cells reform triglyceride to cholesterol forming a chylomicron
• Absorption
  • Chylomicrons
    • Released by exocytosis into lacteals
  • Lacteals

1. Bile salts released from liver and gallbladder emulsify lipid droplets to form micelles
2. Pancreatic lipase functions within micelles to digest each triglyceride into a monoglyceride and two free fatty acids
3. Monoglyceride and free fatty acids enter an epithelial cell, while bile salts remain in the intestinal lumen to be reabsorbed and recycled
4. Triglyceride molecules are reassembled within epithelial cells. Lipids are then wrapped with protein to form a chylomicron. Chylomicrons are packages within secretory vesicles and then exocytosed from the cells and absorbed into lacteals

Nucleic Acids (DNA and RNA)

• Small intestine
  • Nucleases (break phosphodiester bonds) released by pancreas
    • Deoxyribonuclease - DNA
    • Ribonuclease - RNA
  • Brush border enzymes
    • Phosphatase
      • Break bond between phosphate group and sugar
    • Nucleosidase
      • Break bond between sugar and nitrogenous base

Chapter 28: Reproductive System

Reproductive System

• Gonads - ovaries and testes
  • Gametes - sex cells that unite at fertilization (sperm and secondary oocyte)
• Sex hormones
  • Affect maturation, development, and reproductive activity
• Accessory reproductive organs

Sexual maturation

• Puberty
  • Gonadotropin-releasing hormone (GnRH) - hypothalamus; stimulates anterior pituitary to release…
    • Follicle stimulating hormone (FSH)
    • Luteinizing hormone (LH)

Gametogenesis

• Process of forming human sex cells
  • Secondary oocyte - 1 oocyte a month
  • Sperm - 100 million per day to be stored, if not released it gets absorbed in body
• Meiosis
  • Diploid to haploid
• Hereditary information
  • Autosmes
    • Homologous chromosomes (matching pair)
  • Sex chromosomes
  • Diploid cell (2n) - 46 chromosomes
  • Haploid cell (n) - 23 chromosomes

Meiosis

• Meiosis I - separation of homologous pairs
  • Prophase I
    • Synapse (line up)
    • Crossing over “swap genetic material” (diversity)
    • Nuclear envelope breaks down
    • Spindle fibers form
  • Metaphase I
    • Homologous pairs line at equator
    • Spindle fibers attach to centromeres
    • Random alignment
    • Independent assortment (diversity)
  • Anaphase I
    • Pairs pulled to opposite spindle poles
    • Reduction division (46 to 23)
  • Telophase I
    • Cleavage
    • Results in 2 cells each with 23 chromosomes with sister chromatids
• Meiosis II - separation of sister chromatids (single chromosome in haploid cell)
  • Prophase II
    • No crossing over
    • Spindle fibers form
    • Nuclear envelope breaks down
  • Metaphase II
    • Sister chromatids at equator
    • Spindle fibers extend from the centrioles to each sister chromatid
  • Anaphase II
    • Sister chromatids pulled apart at centromere
    • To opposite spindle poles
  • Telophase II
    • 4 new daughter cells produced
    • 23 chromosomes each

Nondisjunction - in meiosis can lead to abnormalities in chromosome number

• Trisomy +1 (47)
• Monosomy -1 (45)
• Trisomy 21 (down syndrome)
  • 1 in 700 children
  • Risk increases as females age

Female Reproductive System

• Primary reproductive organs
  • Ovaries
• Accessory reproductive organs
  • Uterine tubes
  • Uterus
  • Vagina
  • External genitalia
  • Mammary glands

Anatomy of ovaries

• Contain
  • Cortex
    • Ovarian follicles - production of oocyte; release of sex hormones
  • Medulla - ovarian blood vessels, nerves, lymph vessels
• Ligaments
  • Broad - mesa ovarium
  • Ovarian - to broad aspect
  • Suspensory - lateral edge of each ovary; entry of blood vessels and nerves; own ovarian artery and vein.

Ovarian follicles

• Primordial follicle - primary oocyte
  • Single layer of flattened follicular cells surround an oocyte
• Primary follicle - primary oocyte
  • Single layer of cuboidal granulosa cells surround an oocyte
• Secondary follicle - primary oocyte
  • Multiple layers of granulosa cells surround the oocyte
• Antral follicle - primary oocyte
  • Many layers of granulosa cells surround the oocyte and a small antrum develops within layers of granulosa cells
• Mature follicle - secondary oocyte
  • Many layers of granulosa cells surround the oocyte and a very large antrum
• Corpus luteum - no oocyte
  • yellowish, collapsed fold of granulosa cells
  • Release progesterone and estrogen
• Corpus albicans - no oocyte
  • Whitish connective tissue scar, remnant of a degenerated corpus luteum

Oogenesis

• Before birth
  • Oogonia - primary oocytes
    • Divide by mitosis
    • 1.5 million primordial follicles at birth
    • Primary oocytes start meiosis I
  • Prophase I (arrests until puberty)
• Childhood
  • Inactive - atresia
    • 200-400,000 follicles remaining
• Puberty to menopause
  • Folliculogenesis
  • Ovarian cycle
    • Follicular phase - days 1-13
    • Ovulation - day 14
    • Luteal phase - days 15-28
• Perimenopause
  • Irregular or skipped menstrual cycles
• Menopause
  • No menstrual cycle for one year

Ovarian Cycle

• Follicular phase (days 1-13)
  • Formation of one mature follicle (secondary oocyte)
  • Primordial particles mature into primary follicles
  • Increase in FSH, LH release
  • Granulosa cells release inhibin to inhibit FSH
• Ovulation (day 14)
  • One ovary ovulates per month
  • Release of secondary oocyte
  • Peak in LH release
  • Antrum swells which thins the follicle to eventually rupture it
  • Fertilization
    • Completion of meiosis
  • No fertilization
    • Secondary oocyte is broken down
• Luteal phase (days 15-28)
  • Remaining follicular cells
  • Formation of corpus luteum
  • The release of estrogen and progesterone forms the uterine lining (functional layer)
  • No fertilization
    • Regression of corpus luteum
    • Formation of corpus albicans
    • Decrease in estrogen and progesterone
    • Menstruation

Hormonal Interactions of Folliculogenesis and Ovarian Cycle

• Hypothalamus
  • GnRH
• Anterior pituitary
  • FSH and LH
• Ovarian follicles
  • Estrogen
  • Inhibin
• Preantral stage of folliculogenesis

1. Hypothalamus secretes GnRH, which stimulates anterior pituitary
2. FSH and LH target the ovaries and affect ovarian follicle growth
3. a.) maturing preantral ovarian follicles secrete inhibin (which inhibits FSH production) and low levels of estrogen (which inhibit both the hypothalamus and anterior pituitary).

b.) estrogen also assists with the development of the follicle

• Antral stage of folliculogenesis, ovulation, and luteal phase

1. Antral follicle develops, growth now dependent on FSH and LH secretion
2. Mature follicle produces a large threshold amount of estrogen, which stimulates the hypothalamus and anterior pituitary
3. An LH surge form the anterior pituitary induces ovulation
4. The corpus luteum forms under the influence of LH
5. The corpus luteum secretes large amounts of progesterone, estrogen, and inhibin, which inhibit the hypothalamus and anterior pituitary.

Uterine Tubes

• Segments
  • Infundibulum
    • Fimbriae (fingerlike projections)
  • Ampulla
    • Location of fertilization
  • Isthmus
    • ⅓ of tube
  • Uterine part of tube
    • Penetrates uterine wall

Uterus

• Functions
  • Implantation
  • Supports, protects, nourishes embryo
  • Ejects fetus
  • Contacts and sheds lining
• Regions
  • Fundus, Body, Isthmus, Cervix
• Support structures
  • By pelvic floor muscles and ligaments

Tunics of uterine wall

• Perimetrium
  • Continuous with broad ligament
• Myometrium
  • Thick middle year (3 layers within)
• Endometrium
  • Simple columnar epithelium
  • Underlying lamina with uterine glands that enlarge during the cycle
  • Basal layer
    • Permanent layer
  • Functional layer
    • Layer that is shed in menstruation
    • By estrogen and progesterone

Vagina (mucosa, muscularis, adventitia)

• Functions
  • Birth canal
  • Receives penis during intercourse
  • Passageway for menstruation
  • Acidic secretions to avoid secretion
  • Transverse folds

Uterine (menstrual) cycle - 28 days; influenced by estrogen and progesterone

• Menstrual phase (days 1-5)
  • Breakdown of functional layer
• Proliferative phase (days 6-14)
  • Development of new functional layer
  • Increase in estrogen that overlaps follicle growth
• Secretory phase (days 15-28)
  • Increase in estrogen and progesterone
  • Increased uterine wall vascularization
  • Increase in number of uterine glands
  • If no fertilization occurs
    • Decrease in hormones (estrogen and progesterone)
    • Menstruation occurs again

Menopause

• Termination of menstrual cycle
• No more ovarian follicles remain or follicle maturation stops
  • Onset is between 45-55 years old
• Adrenal cortex
  • Produces androgens which are precursor for estrogen
  • Important source of estrogen in postmenopausal women

External Genitalia

• Labia majora
  • Paired thickened folds
  • Homologous to scrotum in males
• Labia minora
  • Internal paired folds
  • Highly vascularized
• Vestibule
  • Space between labia minora
  • Contain urethral opening and vaginal orifice
• Bulb of the vestibule
  • Erectile tissue on either side of vaginal orifice
  • Increases in blood flow during sex
• Greater vestibule glands
  • Homologous to bulbourethral gland in male
  • Secretes mucin which increases in stimulation during sex
• Clitoris - small erectile body that is homologous to the penis
  • Body -
    • from 2 erectile bodies called the corpora cavernosa
  • Crus -
    • elongated masses that extend from corpora cavernosa to pubic arch
  • Glans -
    • cap the clitoral body
  • Prepuce -
    • Hood

Female sexual response

1. Excitement Phase

• PNS innervation of reproductive structures by pelvic splanchnic nerves
  • Mammary glands, clitoris, vaginal wall, bulbs of vestibule, and labia
• Increase in heart rate, blood pressure, and respiratory rate

1. Orgasm

• Pelvic throbbing
• Vagina and uterus contract rhythmically for a period of many seconds

1. Resolution Phase

• Uterus returns to original position and vaginal wall relaxes
• Excess blood leaves other reproductive organs
• No refractory period, potential to have multiple orgasms during one session

Mammary Gland - compound tubulo alveolar exocrine glands

• Components of mammary gland
  • Nipple
    • Multiple tiny openings
    • Allows for excretory ducts
  • Areolar
    • Pigmented ring
    • Uneven surface due to areolar glands
  • Alveoli
    • Produce milk in lactating females
  • Lactiferous ducts
    • Drains a single lobe
  • Lactiferous sinus
    • Milk storage

Male Reproductive System

• Primary reproductive organs
  • Testes
    • Sperm and androgen production
• Accessory reproductive organs
  • Ducts and tubules
  • Accessory glands
  • Penis
• Scrotum - skin covered sac; homologous to labia majora
  • Provides cooler environment
    • For sperm development and maturation
  • Responds to temperature changes
    • High temp:
      • Relax dartos muscle and cremaster muscle
      • Testes move inferiorly
    • Low temp:
      • Contraction of dartos muscle and cremaster muscle
      • Scrotum is pulled towards body to conserve heat
• Spermatic cord
  • Contain blood vessels and nerves

Seminiferous Tubules - within testi, four per lobule

• Sustentacular cells
  • Nourishes developing sperm
  • Release inhibin when sperm count is high to decrease FSH
• Spermatogonia
  • Dividing germ cells that produce sperm
• Interstitial cells
  • Produce testosterone (and adrenal cortex)
    • Stimulated by LH; majority released at puberty

Hormonal Regulation of Sperm Development

• Hypothalamus
  • GnRH
• Anterior pituitary
  • FSH - stimulates sustentacular cells
  • LH - stimulates interstitial cells
• Interstitial cells
  • Testosterone
• Sustentacular cells
  • ABP
  • Inhibin

1. GnRH secreted by the hypothalamus stimulates the anterior pituitary to secrete FSH and LH
2. LH stimulates interstitial cells to secrete testosterone
   1. FSH stimulates sustentacular cells to secrete androgen-binding protein (ABP), which keeps testosterone levels high in the testis
3. Testosterone stimulates spermatogenesis but inhibit GnRH secretion and reduces the anterior pituitary’s sensitivity to GnRH
4. Rising sperm count levels cause sustentacular cells to secrete inhibin, which further inhibits FSH secretion
5. Testosterone stimulates libido and development of secondary sex characteristics

Spermatogenesis and Spermiogenesis

• Spermatogenesis
  • Process of sperm development
  • Spermatogonia
    • Primary spermatocyte (diploid) - primordial germ cells - mitosis
      • Secondary spermatocyte (haploid) - meiosis I
        • Spermatid
• Spermiogenesis
  • Final stage of spermatogenesis
  • Differentiation to fully mature sperm
    • Spermatid to spermatozoa (sperm)
      • Shed cytoplasm
      • Nucleus enlarged
      • Acrosome (digestive enzyme) cap over nucleus
      • Tail forms (connects to midpiece
      • Centriole

1. Germ cells that are the origin of sperm are diploid cells called spermatogonia
   1. Mitotic divisions of these cells produce a new germ cell and a committed cell
   2. The committed cell is a primary spermatocyte
2. Meiosis I begins in the diploid primary spermatocytes
   1. The haploid cells produced during meiosis I are called secondary spermatocytes
3. Meiosis II originates with the secondary spermatocytes and produces spermatids
4. The process of spermiogenesis begins with spermatids and results in morphologic changes needed to form sperm that will be motile

Duct System in the Male Reproductive System

• Rete testis
• Efferent ductules
  • Connect rete testis to epididymis
  • Ciliated columnar epithelium
  • Facilitates sperm movement to epididymis
• Epididymis
  • Pseudostratified columnar epithelium
  • Conduct sperm and seminal fluid toward urethra
• Ductus deferens
  • Unite with seminal vesicle to form ejaculatory duct
• Prostatic urethra
• Membranous urethra
• Spongy urethra
• *sperm do not become motile until it is out of the penis*

Accessory Glands and Semen - time=2 weeks

• Seminal fluid
  • Alkaline fluid as vagina is acidic
  • Nutrients to energize sperm
• Accessory glands
  • Seminal vesicles
    • Alkaline fluid
      • Viscous fluid
    • Fructose
      • Energy
    • Prostaglandins
      • Widen external os of the cervix
  • Prostate gland
    • Milky fluid
      • Mucin
    • Citric acid
      • Nourishment of sperm
    • Seminalplasmin
      • Antibiotics to combat UTIs
    • PSA
      • Prostate-specific antigen
      • Liquifies semen once ejaculated
  • Bulbourethral glands
    • Clear, viscous mucin
      • Coats and lubricates urethra
• Semen
  • Formed from seminal fluid and sperm
    • Turns into “ejaculate” once released from the body
      • 3-5mL of semen that contains 200-500 million sperm

Penis

• Root
  • Internally attached
  • Forms bulb and crus
• Body
  • Elongated movable protein
• Glans
  • External urethral orifice
  • “Tip”
• Prepuce
  • Foreskin
• Erectile bodies
  • Corpora cavernosa (paired)
    • Terminate in the shaft
  • Corpus spongiosum
    • Contain spongy urethra
    • Connect to glans

Male Sexual Response

1. Excitement
   1. Blood fills venous spaces to make the penis erect
   2. Penis is compressed (no blood drainage)
   3. PNS activity
      1. Release of nitric oxide (increases blood flow)
   4. Increase in heart rate, blood pressure, respiratory rate
2. Orgasm
   1. Ductus deferens move sperm to urethra
   2. SNS activity
      1. Ejaculation
3. Resolution
   1. SNS activity
      1. Contract central arteries and muscles around erectile tissues
      2. Blood is expelled

• *males have a refractory period*

Chapter 29: Development, Pregnancy, and Heredity

Prenatal Period - begin with fertilization, end 38 weeks later at birth

• Pre-embryonic period
  • First 2 weeks after fertilization
  • Zygote is becoming a blastocyst
  • Ends when it implants to uterine wall
• Embryonic period
  • Weeks 3 through 8 of development
  • Blastocyst becomes an embryo
  • Systems briefly appear
• Fetal period
  • Remaining 30 weeks prior to birth
  • After 8th week
  • Organs increase in complexity

Fertilization - 3 phases

• Corona radiata penetration
• Zona pellucida penetration
• Fusion of sperm and oocyte plasma membranes and fusion of sperm and ovum pronuclei
• Sperm undergoes capacitation
  • Glycoprotein conditions sperm
• 2nd oocyte releases chemotaxic signals to attract sperm
• Cumulus cells release progesterone binding channels to sperm
  • Increase sodium entry
  • Acrosome reaction
  • Sperm capacitation
• Moves on to 3 phases…

1. Phase 1 (corona radiata penetration):
   1. Sperm penetrates corona radiata
2. Phase 2 (zona pellucida penetration):
   1. Sperm undergoes acrosome reaction and penetrates zona pellucida
3. Phase 3 (fusion):
   1. Sperm and oocyte plasma membranes fuse; pronuclei of ovum and sperm fuse

Pre-embryonic period

• Cleavage - mitotic divisions, increase # of cells not size
  • 8-cell stage
  • Morula
    • 16-cell stage
    • Fluid leak into zona pellucida
    • Formation into a blastocyst cavity
  • Blastocyst
    • Trophoblast
      • Outer ring of cells
      • Chorion layer
    • Embryoblast
      • Inner layer of cells
      • Form embryo layer

Implantation Steps

• Zona pellucida breakdown
• Blastocyst enters endometrium
• Day 7 - trophoblast subdividing
  • Cytotrophoblast
    • Inner layer
  • Syncytiotrophoblast
    • Outer layer that burrows into functional layer of endometrium
    • Produce hCG
      • Signals to corpus luteum on the first trimester of pregnancy
        • Increase in estrogen and progesterone to maintain uterine lining
• Day 8 - cells of embryoblast differentiate (bilaminar germinal disc)
  • Hypoblast
    • Adjacent to blastocyst cavity
  • Epiblast
    • Adjacent to amniotic cavity
• Day 9 - blastocyst completely burrowed in uterine wall

Placenta

• Forms around 2nd week
• High vascularized structure
• Exchange nutrients, waste, gasses
• Fetal portion
  • Chorion
• Maternal portion
  • Functional layer of endometrium
• Connecting stalk
  • Connect early embryo to placenta
  • Umbilical artery and umbilical vein
  • Precursor to umbilical cord

Pregnancy

• First trimester
  • First 3 months
  • Zygote to embryo to early fetus
• Second trimester
  • Months 4-6
  • Growth of fetus
  • Expansion of maternal tissues
• Third trimester
  • Months 7-9
  • Fetus grows rapidly
  • Body prepares for labor and delivery

Labor

• Physical expulsion of fetus and placenta from uterus
• Increase in oxytocin and estrogen
• Premature labor
  • Under 38 weeks
  • Organs not matured in fetus
• False labor
  • Uterine contractions that don’t result in the 3 stages of labor
• Braxton Hicks
  • Random contractions that don’t increase in intensity/frequency
  • No cervical dilation
• True labor
  • Increases in intensity/frequency
  • Cervix dilated to 10cm
• Oxytocin from the fetus and mother’s hypothalamus is secreted
  • Stimulates placenta to make prostaglandins
  • Stimulates uterus to contract
• Prostaglandins stimulate more frequent and intense contractions of uterus
  • Uterine contractions cause the fetal head to push against the cervix, making the cervix stretch and dilate
• Dilating cervix stimulates the hypothalamus to secrete more oxytocin (positive feedback)

Stages of Labor

• Dilation stage
  • Uterine contractions that increase in intensity and frequency
  • Ends at cervix dilated at 10 cm
  • Rupture of amniotic sac
  • Great variability in females
• Expulsion stage
  • Complete dilation of cervix
  • Ejection of fetus out of uterus
  • Crowning
  • Episiotomy may be needed
  • Umbilical cord is cut
• Placental stage
  • Uterus contracts to compress uterus
  • Remove placenta (afterbirth) within 30 minutes of expulsion stage

Fetal positioning

• Vertex
  • Head down
  • Face towards sacrum
  • Ideal positioning
• Breech
  • Buttocks first
  • Delays cervix dilation
• Occiput posterior
  • When head is down
  • Face towards pubic symphysis
  • Harder to extract