ANS and Cell Pathophysiology

The Autonomic Nervous System

part of your body that controls automatic jobs

the ANS regulates moment to moment activity of _______, ________, and _________

smooth muscles

cardiac muscle

various glands

the ANS permits the body to…

adjust to alterations of internal and external environment

the ANS is typically referred to as the _______ nervous system

involuntary

Sympathetic nervous system (SNS)

the part of your body’s ANS that controls the automatic “fight-or-flight” response

What type of outflow does the SNS have (aka where the neurons originate from the spinal cord)?

thoraco-lumbar

What kind of functions does the SNS serve?

survival functions

prepares the body to react to stressful situations

transmitters of the SNS

NE and EPI

Parasympathetic Nervous System (PNS)

the part of your body’s ANS that controls INVOLUNTARY functions and helps your body relax, recover, and conserve energy

What is the outflow of the PNS (aka where do the neurons originate)?

cranio-sacral (originates from the brainstem and sacral region on the spine)

What functions does the PNS serve?

“vegetative functions” and homeostasis

transmitter of PNS

ACh

Describe the PNS pathway:

CNS → ACh → Ganglion → ACh → Tissue

the first preganglionic neuron travels from the CNS to the parasympathetic ganglion and then the preganglionic neuron releases ACh. The ACh then binds to nicotinic ganglionic receptors in the ganglion. The postganglionic neuron travels from the ganglion to the target tissue and also releases ACh. At the target tissue, the ACh generally binds to muscarinic receptors.

Where are parasympathetic ganglion located?

very close to or inside the target organ tissue

Describe the SNS pathway

CNS → ACh → Ganglion → NE → tissue

The preganglionic neuron travels to the ganglia and releases ACh. The ACh binds to nicotinic ganglionic receptors in the sympathetic ganglion. The postganglionic neuron releases NE, and the NE then acts on the target tissue, generally at adrenergic receptors (alpha or beta)

Where are SNS ganglia?

closer to the spinal cord

The second SNS pathway

CNS → ACh → Adrenal Medulla

the preganglionic neuron releases ACh onto the adrenal gland. then the adrenal gland releases EPI into the bloodstream

Somatic Nervous System pathway

CNS → ACh → Skeletal Muscle

the one neuron releases ACh onto the skeletal muscle and the ACh binds to nicotinic muscle receptors on the skeletal muscle.

what are the sympathetic receptors?

alpha-1

alpha-2

beta-1

beta-2

alpha 1 receptor

causes smooth muscle contraction (ex: vasoconstriction)

alpha-2 receptor

decreases further NE release

Beta-1

helps your heart pump faster and harder

Beta-2

causes smooth muscle relaxation, especially in airways → opens the airways

What sympathetic receptors are generally excitatory?

Alpha-1 and Beta-1 responses

What sympathetic receptors are usually inhbitory

Alpha-2 and Beta-2 responses

NE can activate ________________ receptors well, but has little effect on ______ receptors

Alpha-1, Alpha-2, Beta-1

beta-2

What receptors can EPI activate?

all 4

what is discharge?

nerve activity/signaling

• a discharge pattern describes how broadly the nervous system activates its target organs at one time

The discharge pattern of PNS is ____ and ______

limited and discrete

• usually activates one organ or a small group of organs at one time

Discharge Pattern of SNS

1. discrete discharge during heat regulation and vasodilation to skeletal muscle blood vessels

2. massive discharge during fight or flight response

• the body is coordinating multiple organ systems (inc. heart activity, pupil dilation, inc. energy availability) simultaneously to respond to the stressful situation

What occurs in the stress reaction?

inc. HR and CF (contractile force → the heart contracts more strongly)

increased sweating (apocrine glands)

vasoconstriction of cutaneous blood vessels

vasodilation of skeletal muscle blood vessels

bronchodilation

pupillary dilation

coronary vasodilation

glycogenolysis

what receptor is associated with increased HR and CF?

beta-1

What transmitter is associated increased sweating?

activated by EPI

What receptor is associated with vasoconstriction of cutaneous blood vessels?

alpha-1

What receptor is associated with vasodilation of skeletal muscle blood vessels?

beta-2

What receptor is associated with brochodilation?

beta-2

what receptor is associated with pupillary dilation (mydriasis)?

alpha-1 and beta-2

what receptor is associated with coronary vasodilation?

beta-2

what receptor is associated with glycogenolysis?

beta receptors, but mainly Beta-2

Cholinergic Receptors

a receptor that ACh binds to

What receptor does ACh bind to at a PARAsympathetic target organ?

Muscarinic

Do Sympathetic and parasympathetic ganglia have Ng receptors?

Yes!

Nicotinic muscle (Nm)

skeletal muscle

found on the skeletal muscle at the neuromuscular junction

belongs to SNS

What characteristics are associated with PNS?

heart beat slow

digestion increased

drooling due to increased secretions

bronchioles are constricted

erection

tiny pupils

Characteristics associated with SNS?

bronchodilation

increased HR and CF

dec digestion

arterioles in heart dilate to supply blood to latter organs

urine retained

What are the four aspects of the disease process?

• etiology

• pathogenesis

• morphologic changes

• clinical significance (functional consequences of morphological changes)

what is clinical significance regarding the disease process?

what that change does to the patient

aka if the tissue’s structure changes, how does that affect what the tissue is capable of doing

Etiology

what caused the disease

what are the two types of factors that cause diseases (in etiology)?

intrinsic factors

acquired factors

intrinsic factors

causes from within the person

mainly GENETIC factors causing them to have the disease

acquired factors

causes encountered during life

• infectious (microorganisms causing disease such as bacteria, viruses, etc.)

• nutritional (too much or too little of a nutrient. ex: vitamin deficiency)

• chemical (exposure to harmful chemicals such as toxins or poisons)

• physical (physical forces that damage the body ex: trauma, burns, radiation)

T/F: Concept of one disease, one etiologic factor is no longer valid

TRUE

a diseases doesn’t necessarily have one single cause.

• many diseases are multifactorial → this means that multiple factors work together to cause the disease

  • ex: someone developing cardiovascular disease could be influenced by a combo of genetics, nutrition, physical activity

Pathogenesis

how the disease develops after the cause of disease

Pathway of Pathogenesis

initital stimulus (whatever starts the disease process) → sequence of events (all the biological steps that happen afterward) → disease expression (when the disease actually produces detectable changes, signs, or symptoms)

*****this whole chain is Pathogenesis

T/F: does the initial stimulus of a disease immediately produce the disease you see?

FALSE

there can be many intermediate steps between the initial stimulus and disease expression

The time from stimulus to expression is the same for all diseases and all individuals

FALSE

the amt of time between the initial stimulus and when the disease becomes apparent isn’t always the same

• it could be minutes/hours for some or months/years for other

• people with the same disease can also develop symptoms at different rates

morphological changes

what the disease physically changes.

• these are structural changes or changes in appearance in cells, tissues, or organs caused by a disease

can morphological changes be a characteristic of a certain disease?

Yes!

certain diseases produce specific-looking structural changes

• a pathologist might say, “this particular pattern of cell/tissue changes is characteristic of Disease X”

How do morphological changes play a role in the etiologic process?

sometimes the appearance of the damaged cells/tissue gives you clues about what caused the damage

• this means that seeing a particular morphological change can help you infer the likely disease process/cause

  • seeing the morphological changes can help determine whether the process is infectious, inflammatory, etc.

what are functional changes determined by? (4)

specific morphological changes

• ex: damage to heart muscle → heart may not pump as effectively

distribution of the morphological changes

• how much tissue is affected and where is it

rate and order of changes

• if it is a rapid change → potentially causes more serious damage compared to a slow change

ability of body to adapt to changes

How is cell and tissue injury induced (aka what are the 4 major concepts involved in how cells/tissues respond to stress & injury)?

adaptation

cell injury

ageing

cell death

adaptation (cell and tissue injury)

the cell changes itself to handle a new environment or increases/decreases its demand

it survives

ex: a splinter being covered by skin

cell injury (cell and tissue injury)

happens when the stress is too much for the cell to adapt to

can be reversible

ageing (cell and tissue injury)

less capable of maintaining normal function and responding to stress

• repair damage less effectively → more susceptible to dysfunction and disease

• adapt less effectively

• accumulate cell damage over time

cell death (cell and tissue injury)

the injury is too severe or lasts too long and the damage is irreversible

cellular adaptation

change in a cell structure or function in response to changes in the environment

Two types of cellular adaptation

physiological

pathological

physiological cellular adaptaition

a reversible, normal response that allows cells to modify their size, number, or function to handle everyday stress or hormonal changes without being injured

• ex: changes in uterus during pregnancy

pathological cellular adaptation

an abnormal response driven by disease, chronic stress, or injury

• ex: high blood pressure (blood vessels start to get bigger to accommodate)

What is Cellular Injury?

caused by any factor that alters cellular structures and make it not function normally.

what two important things the cell needs and without it, cell injury will occur?

oxygen

nutrients

if cells are deprived of either, they can’t make enough energy or maintain their normal structures

sub-lethal injury

injury not severe enough to kill the cell → reversible injury

lethal injury

damage is too severe for the cell to recover → irreversible damage

what are the 7 classifications of cellular injuries?

chemical

hypoxic (lack of O2)

free radical (oxidative stress or Reactive Oxidative Species)

• too many ROS → damage to things such as cell membranes, proteins,DNA

unintentional

• running into a wall

intentional

• cancer treatments targeting certain cells

infectious agents

• viruses, bacteria, fungi

inflammatory

• closely related to free radicals

• inflammation is supposed to protect the body, but the inflammatory response can sometimes damage surrounding tissues

What are an injured cells two options?

repair or die

What are the three major types of cell death?

apoptosis

necrosis

autophagy

apoptosis

clean, programmed cell death

necrosis

messy, accidental cell death

autophagy

the cell eats itself

• the cell breaks down/recycles its own components

how can cell death be measured?

morphological and biochemical bacteria

Cell death Morphological Criteria

• change in cell size

• the plasma membrane loses integrity, thus the cell can’t keep homeostasis

• organelle membrane integrity

  • same concept as plasma membrane, so damage to structures such as the mitochondria and the nucleus is an important indicator of severe injury

Cell death Biochemical Criteria

leakage of intracellular enzymes

• the enzymes leak out due to the cell membrane being damaged.

activation of proteins that participate in cell injury/death

• caspases (help carry out the controlled dismantling of a cell during apoptosis)

• p53 (evluates cell damage to see if it can fix it)

• proteases (break down proteins)

Why does cellular adaptation occur?

protection

response to injury

what is wrong with an adapted cell?

even though the adapted cell is still alive and functioning, it still has changed from its original state. the adapted cell is not normal, but can better tolerate the stress

What are the 5 types of cellular adaptation?

atrophy

hypertrophy

hyperplasia

metaplasia

dysplasia

atrophy

decrease in cell size

• ex: abby’s quads getting smaller since it wasn’t used for a long time

if enough cellular atrophy occurs, the organ will decrease in size

• seen the most in skeletal muscle, but can also be seen with the heart, secondary sexual organs, and the brain

mechanisms of atrophy

less ER

fewer mitochondria

acidosis

inc in autophagic vesicles (mal-nutrition)

hypertrophy

increase in cell size (physiological and pathological)

• ex; muscles getting bigger from lifting weights

what cells can’t divide?

heart and muscle

• this is why hypertrophy happens here instead of hyperplasia

mechanisms of hypertrophy (in the muscle, kidney, and heart)

more ER

more mitochondria

more myofilaments

increased synthesis of DNA

genetic activation of growth factors, c-fos, c-jun

what signals are present in hypertrophy/

mechanical

• physical stretching/increased workload

trophic

• chemical signals that promote cellular growth

hyperplasia

increase in number of cells (physiological and pathological)

new cells result from cell division

mechanisms of hyperplasia

change in cell cycle

synthesize more DNA
more cellular components

hormonal

hormones activate cellular signaling

where do you see hyperplasia a lot?

skin, liver, and calluses

compensatory hyperplasia

cell divide to regenerate tissue (replacing what was lost)'

• ex: wound healing (cells proliferate to replace damaged tissue), liver (if 70% of the liver is removed, it will grow back)

hormonal hyperplasia

hormonal stimulation causes an inc in cell number

• seen physiologically in estrogen-dependent organs

  • ex: pregnancy: hormonal signals cause certain tissues to grow through increased cell proliferation

pathological hyperplasia

excessive/abnormal proliferation (too many are being produced)

increased receptors for growth factors → increased sensitivity to growth promoting signals → more cell division

ex: endometrium: excessive estrogenic stimulation → endometrial cell proliferation → endometrial hyperplasia and can cause abnormal/heavy uterine bleeding

Benign Prostate Hyperplasia (BPH)

noncancerous inc in the number of cells in the prostate → causes the prostate to enlarge

• causes urinary problems, restricted urine flow, feeling like the bladder isn’t completely empty

metaplasia

reversible replacement of a mature cell by another (change in type of cell)

• ex: this cell isn’t handling the environment well → lets replace it with different cell type that can better handle the stress. however, the new cell could have potentially less specialized function

mechanisms of metaplasia

re-programming of founder or stem cells that make up tissue

• the cell follows a different differentiation pathway and matures into a different type of cell

precursor cell matures along a different pathway

can lead to cancer

• if the harmful stimulus continues for a long time, the tissue can accumulate additional abnormalities