Cellular Pathophysiology and Autonomic Nervous System 1

what is pathogenesis

understanding the progression of different diseases and conditions at the cellular level

As a PT, what should we take into account when learning about the effects of a disease

- the person's functional abilities and limitations

- our focus in on allowing the person to maintain a healthy life

what is the health of an individual dependent on

healthy behaviors, genetics, social factors, support systems, and the disease or condition the person has (multi causal factors)

what are the two factors that cause a cell injury

stress or injury stimulus

if a cell is injured and can bounce back from its losses, what is this called

reversible injury

what happens with cell irreversible injury

necrosis and apoptisis

what is ischemia

insufficient blood flow (to maintain homeostasis) that leads to hypoxia or anoxia, decreased delivery of nutrients, and decreases removal of waste products

what is the difference between hypoxia and anoxia

- Hypoxia: low oxygen

- Anoxia: no oxygen

what are the two main infectious agents that cause cell injury

bacterial and viral

what is the difference between viral and bacterial infections

- Viral: site to package process to disrupt the cells function

- bacterial: release toxins that injure the cell

what is the importance of immune reactions in cell injury

our immune cells become overzealous and start attacking healthy cells

what are the components of mechanical stress that cause cell injury

repetitive or a single load that exceeds the failure tolerance of a tissue

true or false: decrease in mechanical stress can be harmful

true! lack of stress will make our tissues weaker!

true or false: nutritional imbalances can lead to cell injury

true!

how can chemical factors cause cell injury

- injure the cell directly (Mercury)

- metabolic transformation into a toxic agent (reactive oxygen species)

what is a new chemical that may be important to modulate physiologic responses

nitric oxide (NO) bioavailibility due to exercise

true or false: psychosocial factors play a role in our ability to prevent injury

True! maintaining a healthy lifestyle will help in injury prevention

what are the primary factors in a reversible cell injury

- an increase of intracellular Na+ and Ca2+

- this causes an influx of interstitial fluid into the cell and causes a swelling

- swells mitochondria

- increase in pH of the cell

- NUCLEUS STAYS INTACT

what is the purpose of cellular adaptations

they occur to allow the cell to regain function after injury

what is atrophy

decrease in the size of the cell or organs

what is hypertrophy

- increase in the size of the cell or organs

- CAN ONLY OCCUR IN THE HEART OR STRIATED MUSCLES (THESE CELLS CANNOT DIVIDE)

what is hyperplasia

increase in the number of cells, and therefore organ size

what is metaplasia

- damage to the cell's morphology and function

- can convert into another cell type

- think of smoker cell morphology change

what is dysplasia

increase in cell numbers with a change in morphology

what are the two main types of irreversible cell injury

necrosis and apoptosis

what is the main difference between necrosis and reversible cell injury

- degradation (pyknotic) of the nucleus

- plasma membrane leakage

- mitochondria swell and fill with Ca2+ deposits (no longer produce ATP)

what is apoptosis

programmed cell death

what is the purpose of inflammation

- inactivate injurious agent

- break down and remove dead cells

- initiate healing

what is acute inflammation

immediate response to cell injury

what is chronic inflammation

when inflammation persists

what are the 4 cardinal signs of inflammation

- erythema: increased blood flow

- heat

- edema: fluid and cells leaking from blood vessels to extravascular space

- pain**: pressure on nerves secondary to edema**

what are the two outcomes of acute inflammation

- complete resolution

- fibrosis: scarring due to pus formation (loss of function)

As a PT, what is our main goal when treating chronic inflammation

help regain normal function even though structure of the tissue may be damaged

true or false: after an internal bleeding event, an intrinsic and extrinsic pathways is used to form a clot

True!

Intrinsic pathway clotting

factor XII > prothrombin > thrombin

extrinsic pathway clotting

thrombin > fibrinogen > fibrin > clot

why is a clot formed in a mesh like structure

to maintain a balance between too much hemorrhage and too much clotting

what is the implication of inflammation in a PT setting

various forms of physical activity can decrease both acute and chronic inflammation

what is tissue healing

- regeneration of initial tissue

- repair of tissue leading to scarring

what is the primary purpose of phagocytes during the inflammation process

- secrete degrading enzymes

- remove debris and dead tissue

what are the three major components in tissue healing

fibronectin, collagen, and proteoglycans and elastin

what is the purpose of fibronectin

provide a scaffold for the other components of tissue healing

what is the purpose of proteoglycans and elastin

- bind to fibronectin and collagen to stabilize tissue being repaired

- helps keep tissue hydrated during repair

what is the purpose of collagen

provides structural support and tensile strength for the body

when collagen is in a parallel formation it provides ______

strength

when collagen is in a random manner, it provides ______

flexibility

what is type 1 collagen

- thick bundles

- mature scars

- tendons and bones

what is type 2 collagen

- thin supporting filaments

- in tissues with cartilage

what is type 3 cartilage

- thin and supple

- make tissues strong, but supple and elastic

what are some important factors influencing tissue healing

health of the individual, alcohol or drug use, nutrition, type of tissue, etc.

what are the 4 stages of tissue healing

- hemostasis and degeneration

- inflammation

- proliferation and migration

- remodeling and maturation

true or false: the 4 phases of tissue healing can overlap each other

True!

what are the hallmarks of hemostasis

- occurs within seconds to hours

- vasoconstriction

- platelet aggregation for clotting and release of growth factors

- leukocyte migration (sets up stage for healing)

what are the hallmarks of inflammation

- occurs within hours to days

- brings fluid to the area

- neutrophils, macrophages, and phagocytes aggregate to clear debris

- angiogenesis begins

what are the hallmarks of proliferation

- occurs within days to weeks

- fibroblast proliferation, collagen synthesis, ECM reorganization

- new blood vessel formation continues

- granular tissue formation

what are the hallmarks of remodeling

- occurs within weeks to months

- ECM is remodeled

- epithelialization

- tensile strength of wound increases

what is healing by primary intention

- initial union of edges of the wound

- minor cuts

- no granular tissue formation

- no separation of skin

what is healing by secondary intention

- larger tissue defects

- surgical closure not possible

- long healing process

what is healing by tertiary intention

- delayed closure fills gap between edges

- large granulation tissue

- presence of keloids in scar (large amounts of excessive collagen in thick bundles)

what is tissue repair

to return the tissue to its original function

what is peripheral nerve repair

- myelin degeneration and axonal fragmentation

- Wallerian degeneration: macrophages are recruited to clear debris from injury

- schwann cell proliferation and axonal sprout formation

what is skeletal muscle repair

- satellite cells

- hemostasis

- phagocytosis

- regeneration

what is the initial injury response to a broken bone

- hematoma

- immediate vascular response

- delivers fibroblasts, platelets, osteoprogenitor cells, and growth factors to the cells

- transform initial hematoma into granulation tissue

what happens during the inflammatory phase of bone healing and repair

- granulation begins

- fibrin network develops and forms a scaffold

- phagocytosis, neovascularization, initial fibrosis

what happens in the reparative phase of bone healing and formation

- soft callus begins to form (by periosteum and endosteum)

- osteoclasts clear necrotic tissue

- bone growth factors

- endochondral ossification: conversion of soft callus to hard callus

what happens during the remodeling phase in bone healing and repair

- union of bone so there is no motion at the fracture site

why is the tendon so weak during its healing

- when a tendon is healing, immobilization is required

- during immobilization, there will be collagen formation in random patterns, making the tendon much weaker than it used to be

how long does it take for tendons and ligaments to heal

between 40-50 weeks

how does cartilage heal

- a fibrous scar forms

- this scar can lead to damage or arthritis

what are the main components of the meniscus

- water and type 1 collagen

- provide lubrication, and provides resistance to compressive forces

how does the meniscus heal

- migration of cells from the synovial membrane

- amount of proteoglycans increase in injured meniscus

what can happen if the synovial membrane is injured

- hemorrhage, hypertrophy, hyperplasia

- hypertrophies can form adhesions between itself and the adjacent articular cartilage

what is the structure of a vertebral disk

- outer annulus (type I collagen)

- inner annulus (type II collagen)

- nucleus (type II collagen and water)

- resists tension and compression

- blood supply limited to the outer annulus for the most part

what are the implications of tissue repair for PTs

- control of edema

- protected rest during inflammatory stage

- increase of tensile force

what is the effect of prolonged immobilization

damaged tissue

what is the somatic nervous system

- voluntary

- motor system under conscious control

- pathway: motor neuron and skeletal muscle fiber

what is the autonomic nervous system

- involuntary

- modulates function and visceral system

- pathway: preganglionic and postganglionic neuron

what are the hallmarks of the preganglionic neuron

- cell body resides in the central nervous system

- axons synapse on cell bodies of post ganglionic neurons outside of the central nervous system

- ALL release acetylcholine

what are the hallmarks of the postganglionic neuron

- axons travel to the periphery

- synapse on visceral effector organs

- release acetylcholine, norepinepherine, or neuropeptides

what are the two categories of the autonomic nervous system

sympathetic and parasympathetic nervous system

where do preganglionic neurons of the sympathetic divison originate

thoracolumbar region

where do preganglionic neurons of the parasympathetic division originate

cephalocaudualy (brain stem and sacral regions)

what are adrenergic neurons

- release norepinepherine

- synapse on effector organs that have adrenoreceptors

what are cholinergic receptors

- release acetylcholine

- attach to receptors called cholinoreceptors

true or false: all preganglionic neurons are cholinergic

True! all preganglionic neurons release acetylcholine

true or false: postganglionic neurons can only be adrenergic

False! postganglionic neurons can release both norepinepherine and acetylcholine, therefore can be both cholinergic and adrenergic

what is the function of the sympathetic nervous system

- fight or flight

- increased metabolic rate

- increased arterial pressure

- increased blood flow to active muscles

- increased mental activity

- increased blood-glucose concentration

true or false: the sympathetic nervous system prepares us for regular exercise activities

True! we rarely have a situation where fight or flight kicks in, and the sympathetic nervous system often works with our heart, lungs, and GI tract to prepare us for exercise

where can we find the autonomic ganglia of the sympathetic nervous system

- paravertebral: synapsing with postganglionic neurons at the same level

- prevertebral: travel to different plexuses in order to synapse with the effector organ

what is the length of preganglionic and postganglionic neurons in the sympathetic nervous system

- preganglionic: short

- postganglionic: long

what is the neurotransmitter and receptor type for the sympathetic nervous system in the ganglion

acetylcholine and nicotinic receptors

what is the neurotransmitter of the sympathetic nervous system in effector organs

- norepinepherine (adrenaline)

- except in sweat glands

what is the receptor type for the sympathetic nervous system in effector organs

alpha 1, alpha 2, beta 1, and beta 2