###### tags: `生理學`
Stay Hungry, Stay Foolish
求知若渴，虛心若愚。
# 生理學 second term

## CH7
### !!Sensory Receptors
:::danger
- Mechanoreceptors(機械接受器)
- Thermorecptors(熱接受器)
- Photoreceptors(光接受器)
- Chemorecepetors(化學接受器)
- Nociceptors(傷害接受器)
:::

### coding
Coding is the conversion of stimulus energy into a signal that conveys the relevant sensory information to the central nervous system.
**Important characteristics of a stimulus include the type of input it represents, its intensity, and the location of the body it affects.**

### !!!cortical association areas
:::danger
The primary somatosensory cortex relies upon various cortical association areas to properly process sensory information.

The region of association cortex closest to the primary sensory cortical area processes the information in fairly simple ways and serves basic sensory-related functions. Regions farther from the primary sensory areas process the information in more complicated ways by contributing **arousal(喚醒), attention(專注), memory(記憶), language(語言), emotion(情緒), and motivation.**
離主要sensory areas的區域利用....處理更複雜的訊息
:::

### Factors that affect perception
- Lack of receptors for certain stimuli
- Damaged neural pathway
- Drugs
- Mental illness(疾病) such as schizophrenia(精神分裂症)

### !!!Somatic Sensation (體接受器)
:::danger
- Sensation from the <span style="color:red">**skin, skeletal muscles, bones, tendons and joints - somatic sensation**</span> - is initiated by a variety of sensory receptors collectively called somatic receptors.

- Activation of somatic receptors gives rise to the sensations of:
- Touch and pressure
- Awareness(意識) of the position of the body parts and their movement
- Temprature
- Pain
- Itch(搔癢)
:::

### Pain Management
- **Analgesia** is the selective suppression(抑制) of pain without effects on consciousness(知覺) or other sensation.

- We use many mechanisms to achieve pain relief:
- **Electrical stimulation** of specific areas of the central nervous system
- **Pharmacological agents (NSAIDS like Tylenol) and morphine (opioids)**
- Release of morphine-like **endogenous opioids** from some of neurons in the inhibitory pathways
- **Acupuncture**針灸(seem to be linked to activation of endogenous opioid pathways)
- **Transcutaneous(經過皮膚的) electrical nerve stimulation (TENS)**
- **Hyperalgesia** is an increased sensitivity to painful stimuli.

### Itch
Itch can be an acute sensation like that associated with a **mosquito bite**(蚊子叮咬),or a persistent(持久性) one associated with inflammatory conditions(發炎症狀) of the skin like eczema(濕疹).

### Vision
The eyes are composed of
- an optical component, which focuses the visual image on the receptor cells
- a neural component which transforms the visual image into **pattern of graded and action potentials**

### Refraction (屈光)

### !!!Correction(矯正) of Vision Defects(缺陷)
:::danger
#### 近視矯正
- Myopic 近視
> - Accommodation(調適)
> - Astigmatism(散光)
> - Glaucoma (青光眼)

#### 遠視矯正
- Hyperopic 遠視
> - Cataract 白內障
> - Presbyopia (老花眼)

:::

### Organization of the Retina
- Rod 柱細胞(看黑白)
- Cone 椎細胞(看色彩)

### Neural Pathways of Vision
- Light signal are converted into action potentials through the interaction(相互作用) of photoreceptors with bipolar cells and ganglion cells

### Effects if light on sinaling in ON-Pathway and OFF-Pathway Ganglion cells

**The coexistence of these ON- and OFF-pathways in each region of the retina greatly improves image resolution by increasing the brain’s ability to perceive contrast at edges or borders.**
#### ON-Pathway
- Photoreceptor is depolarized in absence(沒有) of light rays(光線)
- Light hyperpolarizes photoreceptor cell
- Decreased glutamate release onto bipolar cell
- **Reduced inhibition of glutamate receptors; bipolar cell spontaneously(自發) depolarizes and releases more excitatory neurotransmitter**
- **Ganglion cell depolarize and generates more action potentials**

#### OFF-Pathway
- Photoreceptor is depolarized in the absence of light rays
- light hyperpolarizes photoreceptor cell
- Decreased glutamate release onto bipolar cell
- **Reduced excitation by glutamate receptors; bipolar cell spontaneously hyperpolarizes and release less excitatory neurotransmitter**
- **Ganglion cell hyperpolarizes and generate fewer action potentials**

### Neural Pathways of Vision(4)
**melanopsin(黑色素)** carries visual information to the suprachiasmatic nucleus(視交叉上核), which lies just above the **optic chiasm(視覺交叉點)** and functions as part of the **“biological clock.”(生理時鐘)**

### !!!Visual Pathways and Fields
:::danger
Optic chiasm 視交叉
:::

### Color vision
- Color vision begin with activation of the photopigments in the cone photoreceptor cells. **Human retinas** have three kinds of cones RGB.

- Our ability to discriminate color also depends on the intensity of light striking the retina. In brightly lit conditions, the differential response of the cones allows for good color vision. In dim light, however, only the highly sensitive rods are able to respond.

### !!!Color Blindness (色盲)
:::danger
- There are several types of defects in color vision that result from **mutations in the cone pigments**. The most common form of color blindness, **red-green color blindness**, is present predominantly in men, affecting 1 out of 12.
- Color blindness results from a **recessive mutation(隱性)** in one or more genes encoding the cone pigments.
:::

### eye movement
fast and low
- **The fast movements**, called **saccades**(眼球震顫), are small, jerking(抽蓄) movements that rapidly bring the eye from one fixation point(固定點) to another to allow a search of the visual field.
- Saccades also occur during certain periods of **sleep when dreaming occurs**, though these movements are not thought to be involved(不被認為) in “watching” the visual imagery of dreams.
- **Slow eye movements** are involved both in tracking visual objects as they move through the visual field and during compensation for movements of the head.

### Macular Degeneration (黃斑退化)
- The **macula lutea region(黃班區域)** of the retina is specialized in several ways to provide the highest visual acuity (最高視力)
- This region becomes impaired in a condition known as **macular degeneration**, producing a defect characterized by loss of vision in the center of the visual field.
- The most common form of this disease increases with age, occurring in approximately 30% of individuals over the **age of 75**, and is therefore **referred to as age-related macular degeneration (AMD).** 與年齡相關的疾病

### Audition
- The sense of audition (hearing) is based on the physics of sound and the physiology of the external, middle, and inner ear, the nerves to the brain, and the brain regions involved in sensing and perceiving acoustic information(聲音訊息).
- Sound energy is transmitted through a gaseous(氣態), liquid(液態), or solid medium(固態) by setting up a vibration(震動) of the medium’s molecules, air being the most common medium in which we hear sound energy
> 透過氣態、液態、固態介質的震動來傳播，空氣是我們聽到聲音最常見的介質。
- When there are no molecules, as in a vacuum(真空), there can be no sound.

### !!!Cross section of the membranes and compartments of the Cochlea(耳蝸) with detailed view of the hair cells and other structures on the basilar membrane
:::danger
:::

### Neural Pathways in hearing
- Cochlear nerve fibers synapse with interneurons in the **brainstem.**
> 耳蝸神經纖維與腦幹的中間神經元發生突觸
- From the brainstem, a multineuron pathway transmits information through the **thalamus(視丘)** to the **auditory cortex(聽覺皮層)** in the **temporal lobe(顳葉)**.

### !!!Vestibular Information and Pathways
:::danger
這題有考
- **Vestibular information is used:**
- **to control eye movement**
- **to maintan upright(直立) posture and balance**
- **to provide awareness of body position and acceleration as well as spatial information**

Vestibular nerve fibers transmit information through the brainstem and thalamus to the vestibular centers in the parietal lobe(頂葉) of the cerebral cortex.
> 前庭神經纖維通過腦幹跟視丘向大腦皮層頂葉的前庭中心傳遞訊息

Vestibular information is integrated with sensory information coming from proprioceptors.
- **Nystamus(眼球震顫),unusual vestibular input, High blood ethanol(高血脂)**
:::

### Taste Receptors
- Taste (**gustation味覺**) occurs because of taste buds(味蕾) found in the mouth and throat.
- Taste buds are small groups of cells arranged like orange slices around a hollow taste pore.
> 味蕾像橘子片一樣排列在空心味孔旁的小群細胞
- At the bottom of taste buds are **basal cells**, which divide and differentiate to continually replace taste receptor cells damaged in the occasionally harsh environment of the mouth.
> 在味蕾的底部是基底细胞，它的分裂和分化不断取代在口腔偶尔的恶劣环境中受损的味觉感受器细胞。

### Type of taste receptors
- Many different chemicals can generate the sensation of taste by differentially activating a few basic types of taste receptors:
- sweet
- sour
- salty
- bitter
- **umami** (pronounced “ oo-MAH-mee ”)(鮮味)
> This latter category gets its name from a Japanese word that can be roughly translated as **“delicious.”**

### Signaling of Taste Receptors
- Salt taste is detected by sodium influx
- Sour taste is detected by hydrogen ios blokcing K+ efflux
- Sweet is detected by binding of glucose to G-protein-coupled receptors
- **Bitter flavor is associated with many poisionous substances**, especially plant alkaloids like strychnine and arsenic. These substances activate G-protein mediated second-messenger pathways.
- Umami receptors cells also depolarize via a G protein-coupled recepotor mechanism

### Olfactory Receptors(嗅覺受器)
- The olfactory receptor neurons lie in the The **olfactory epithelium** in the upper part of the nasal cavity(鼻腔).
- Olfactory receptor neurons **survive for only about two months**, so they are constantly being **replaced by new cells produced from stem cells in the olfactory epithelium.**
- **Cilia(纖毛)** contain receptor proteins that provide the binding sites for odor molecules(氣味分子).
:::danger
這題有考
The axons of the neurons form the olfactory nerve, which is cranial **nerve I.**
:::

### Smell
For humans to detect an **odorous(氣味)** substance (an odorant), molecules of the substance must first diffuse into the air and pass into the nose to the region of the olfactory epithelium.

### !!!Factors that Affect the Sense of Smell
:::danger
這題有考
Olfactory discrimination varies with:
- attentiveness
- **hunger**(sensitivity is greater in hungry subjects)
- **gender** (women in general have keener olfactory sensitivities than men)
- **smoking** (decreased sensitivity has been repeatedly associated with smoking)
- **age** (the ability to identify odors decreases with age, and a large percentage of elderly persons cannot detect odors at all)
- **state of the olfactory mucosa** (the sense of smell decreases when the mucosa is congested(黏膜充血) as in a head cold(感冒))

Some individuals are born with **genetic defects(遺傳缺陷)** resulting in a total lack of the ability to smell **(anosmia,嗅覺缺失症)**.
:::

## CH8
### States of Consciousness(意識狀態)
- States of consciousness refers to levels of alertness such as **awake, drowsy, asleep**
- defined in two ways
- by behavior, covering the spectrum(光譜) from maximum attentiveness to comatose
- by the pattern of brain activity that can be recorded electrically
:::danger
An electrical recording, the **electroencephalogram**(腦波圖),portrays(描繪) the electrical potential difference between different points on the surface of the scalp(頭皮)
:::

### !!!EEG
:::danger
這題有考
The majority of the electrical signal recorded in the EEG originate in the <span style="color:red;">**pyramidal(椎體) cells of the cortex.**</span>
:::

### Epilepsy(癲癇)
- epileptic seizure(癲癇發作)
- **Epilepsy** is common neurological disease. It manifest in mild, intermediate, and severe forms and associated with abnormally synchronized **discharges of cerebral neurons**.
- Epilepsy is also associated with **involuntary(不自主) muscle contraction** and a **temporary loss of consciousness**

### The waking state
- **awake**, relaxed adult whose eyes are closed, is an oscillation of 8 to 12 hertz, known as the **alpha rhythm**.
- alpha rhythm is best recored over the **parietal(頂葉) and occiptial lobes** and is associated with decreased of attention. commonly they feel **relaxed and happy**.
- attentive to an **external stimulus** or are thinking hard about something, the alpha rhythm is replaced by smaller-amplitude, **higher-frequency(>12 hertz)** oscillations,the **beta rhythm**

### Sleep
- As a person becomes increasingly drowsy, his or her wave pattern transitions from a **beta rhythm to a predominantly alpha rhythm**
- When sleep actually occurs, the EEG shift towar **lower-frequency, larger-amplitube** wave patterns known as **theta rhythm(4 to 8 hertz)** and the **delta rhythm(slower than 4 hertz)**
- There are two phases of sleep: **NREM(non-rapid eye movement) and REM(rapid eye movemetn) sleep**

### NREM
- **In stage N1 sleep**, **theta wave** begin **to** be interspersed among the **alpha pattern**.
- **In stage N2 sleep**, high-frequency bursts called **sleep spindles** and large-amplitude **K complexes** occasionally **interrupt the theta rhythm**.
- **In stage N3 sleep**, **delta** waves **appear** along **with** the **theta** rhythm; as **this stage continues**, the **dominant pattern becomes a delta rhythm**, sometime referred to as slow wave sleep.

Sleep begin with the progression from state N1 to stage N3 of NREM sleep which normally **takes 30 to 45 minute.**

### REM
- REM sleep is also called **paradoxical sleep**, EEG pattern shows intense activity that is similar to that observed in the alert,**awake state.**
- When awakened during REM sleep, subject frequently report that they have been **dreaming.**

### !!!Coma(昏迷) and Brain Death(腦死)
:::danger
- **Coma** describes an **extreme decrease in mental function** due to structural, physiological, or metabolic impairment of the brain.

- **Brain death** occurs when the **brain no longer functions** and appears to have no possibility of functioning again.
:::

### Selective attention(選擇性注意)
- avoid the distraction of irrelevant stimuli while **seeking out and focusing on stimuli** that are momentarily important

### AD/HD(注意缺失/過動症, attention-deficit/hyperactivity disorder)
- most common neurobehavioral problem **in school-aged chidren**
- difficulty in maintaining selective attention and or **impulsiveness(衝動) and hyperactivity(過動)**
- have indicated dysfunction of brain region in which **catecholamine** signling is prominent, including **the basal nuclei and prefontal cortex**
- medication used to treat AD/HD is **methylphenidate(Ritalin)** increases synaptic concentrations of **dopamine and norepinephrine**

### Motivation(動機) and Emotion(情緒)
- Motivations are the process responsible for goal-directed quality behavior
- Emotion result from the relationship between and individual and the environment

### Motivation
- **Primary motivated behavior** is behavior releated directly to **homeostasis**, such as **getting something to drink when yor are thirsty**

### !!!Chemical mediators of motivation
:::danger
- <span style="color:red;">**Dopamine**</span> is a major neurotransmitter in the pathways that mediate the brain reward systems and motivation
- **Amphetamines** are example of a drug that is abused because they **increase the presynaptic release of dopamine(providing positive reinforcement)**
- **chlorpromazine**, an **antipsychotic drug that blocks dopamine receptors** and lowers activity in the catecholamine pathway, are **negatively reinforcing.**
:::

### Emotion (1)
- Emotional behavior(情緒行為) can be studied more easily than the anatomical(解剖) system or **inner emotions(內在情緒)** because it include s responses that can be measured externally
- Certain anatomical structures in the brain are responsible for emotional response; for example, the <span style="color:red;">**amygdala is responsible for the emotion of fear.**</span>
- The <span style="color:red;">**cerebral cortex has a major function**</span> in directing many of the motor responses during emotional behavior(example, whether you approach or avoid a situation)

:::danger
- **forebrain strutures**, including the **cerebral cortex**, account the **modulation, direction, understanding, or even inhibition of emotional behaviors**
- Although **limbic areas** of the brain seem to handle inner emotions, **there is no single "emotional system"**
> the Limbic System(邊緣系統) That Are Involved in Emotion, Motivation, and the Affective Disorders
:::

### Altered states of consciousness
- refers to unusual sensations such as those occurring woth hypnosis(催眠), mind-altering drugs, and certain diseases such as psychiatric illnesses

### !!!Schizophrenia (精神分裂症)
:::danger
- a disease in which informaiton is not properly regulated in the brain
- The amazingly diverse(各式各樣) **symptoms**(症狀) of schizophrenia include <span style="color:red;">**hallucinations(幻覺)**</span>, especially **"hearing" voices**, and **delusions**(幻想), such as the belief that one has been **chosen for a special misson** or being **persecuted(迫害) by others.**
- **become withdrawn(孤僻), are emotionally unresponsive,and experience inappropriate moods.** They may also experience abnormal motor behavior, which can include **total immobilization(catatonia全身僵直)**.The symptoms vary from preson to person.(症狀因人而異)
- The **cause** of schizophrenia **remain unclear**. It reflects a **developmental disorder(發育障礙)** in which neurons migrate or mature **abnormally during brain formation.**
- suggest that certain mesocortical(中皮層) dopamine pathways are overactive. by fact that **amphetamine-like drugs make the symptoms worse**. by the fact that most drugs treating **block dopamine receptors**
:::

### !!!Depression(憂鬱症) and Bipolar Disorder(躁鬱症)
:::danger
- **depressive disorder** (depression) are a pervasive felling of emptiness or sadness; a loss of energy, interest, or pleasure; anxiety; irritability(易怒); an increase or decrease in appetite(食慾); disturbed sleep; and thoughts of death or suicide
- Bipolar disorder is characterized by swings between **depression and mania**
- Maina is characterized by an abonormally and persistently elevated mood(情緒高漲).
:::
### !!!Depression
:::danger
- It is **associated** with **decreased neuronal activity and metabolism** in the **anterior(前面) part of limbic system and nearby prefrontal cortex.**
- Although **the major biogenic amine neurotransmitters(norepinephrine, dopamine, and serotonin) and acetylcholine** have all been implicated, the cause of the mood disorder are unknown.
- Three types of anti-depressant drugs
- **tricyclic antidepressant drugs(TCA) such as Elavil, Norpramin, and Sinequan** interfere(干擾) iwth serotonin and/or norepinephrine reuptake by presynaptic ending
- The **monoamine oxidase (MAO)** inhibitors interfere with enzyme responsible for the breakdown of these same two neurotransmitters.
- **serotonin-specific reuptake inhibitors(SSRIs)** are the most widely used antidepressant drugs and include **Prozac**, **Paxil** and **Zoloft**, these drugs selectively inhibit serotonin reuptake by presynaptic terminal
:::

### Bipolar Disorder
:::danger
- Episodes of mania are characterized by an **abnormally persistently elevated mood, sometimes with euphoria, racing thoughts, excessive energy, overconfidence, impulsiveness, insomnia, and irritability**
- major drug used in treating is the chemical element <span style="color:red;">**lithium**</span>, sometimes given in combination with **anticonvulsant drugs**.(抗癲癇藥物)
> lithium has been used for more than 50 years, and yet its mechanism of action is not completely understood
:::

### Tolerance(耐受性)

### Substance use disorders
- Although **dopamine is the major neurotransmitter** implicated in substance use disorders, other neurotransmitters, including **GABA, enkephalin, serotonin, and glutamate, may also be involved**

### learing and memory
- learing is the acquisition(收穫) and storage of information as a consequence of expreience
- memory is the relatively premanent storage form of the learned

### Memory
- **Declarative memory** (explicit memory) is the retention and recall of conscious experiences that can be put into words(declared).
- The <span style="color:red;">hippocampus, amygdala, and other parts of the limbic system</span> are required for the formation of declarative memories.
- **Many area of association cortex**
- **procedural memory**, can be defiend as the memory of how to do things.
- This is the memory for **skilled behaviors** independent of any conscious understanding, as for example, **riding bicycle**
- also includes learned **emotional response**, such as **fear of spiders**, and the **classic example of Pavlov's dogs.**
- The primary areas involved are regions of <span style="color:red;">**sensorimotor cortex, the basal nuclei and cerebellum**</span>

### Short-Term memory
- **Working memory**, also known as **short-term memory**, registres and retains incoming incormation for a short time -- a matter of **seconds to minutes** -- after its input.
- Short-term memories may be converted into **long-term memories**, which may be stored for **days to years** and reacalled a later time.
- shor to long-term meomories is called <span style="color:red;">**consolidation**</span>

### retrograde amnesia(回溯性失憶)
頭部被打，中間的記憶全消失。
Short-term memory is interrupted when a person becomes unconscious from a blow to the head, and memories are abolished for all that happened for a variable period of time before the blow, a condition called **retrograde amnesia** .(回朔性失憶) . (**Amnesia is defined as the loss of memory**.)

### anterograde amnesia(前導性失憶
- **It result from damage to the limbic system and associated structures.**
- Patient with anterograde amnesia **lose their ability to consolidate short-term decalarative memories into long-term memories**.

### Cerebral Dominance and language
- **left hemisphere** is specialized to produce and comprehend(理解) **language**
- Language function are in the lefe hemispher in the **temporal, parietal, and frontal cortex next to Sylvian fissure**, which separates the temporal lobe from the frontal and parietal lobes
- suffered brain damage and, as a result, have one or more **defects in language**, inlcuding **aphasia(失語症)** and **aprosodia**

### damage to Wernicke's area and Broca's area
- **Wernicke's area** generally result in aphasias that are more closely related to **comprehension** -- the individuals have **difficulty understanding spoken or written language**.
- **Broca's area**, the language area in the **frontal cortex** responsible for the articulation of speech, can cause **expressive aphasias**

:::danger
Difference between the two hemispheres are usually masked by the integration that occurs via the <span style="color:red;">**corpus callosun**</span> and other pathways that **connnect the two sides of the brain**
:::

## CH10
### Voluntary and involuntary
- involuntary movements (非自主運動) are often characterized as unconscious, automatic, or reflex.

### The withdrawal reflex(退縮反射)
- **Painful stimulation of the skin**, as occurs from stepping on a tack(大頭針), **activates the flexor muscles and inhibits the extensor muscle of the <span style="color:red;">ipsilateral(同側)</span> leg(on the same sige of the body)**
- the resulting action moves the affected limb(四肢) away from the harmful stimulus and is thus known as a **withdrawal reflex**.
- The same stimulus cause just the opposite response in the **contralateral(對側)** leg(on the opposite side of the body from the stimulus)
- extensors are activated while the flexor muscle are inhibited. This **crossed-extensor reflex** enables the contralateral leg to suppot the body's weight at the injured foot is lifted by flexion.

### cerebral cortex
- A network of connected neurons in the frontal and parietal lobes of the cerebral crotex has a critical function in both the plaaing and ongoing control of voluntary movements, functioning in both the highest and middel levels of the motor control hierarchy(層次).

:::danger
這題有考
- A large number of neurons that five tise to descending pathways for motor control come from two areas of sensorimotr cortex on the posterior part of the frontal lobe: **primary motor** cortex(sometimes called simply the motor cortex) and the **premotor area**
:::

### cerebral cortex2
- **supplementary motor cortex(輔助運動皮質)**, which lies mostly on the surface of the frontal lobe where the cortex folds down between the two hemispheres, **somatosensory cortex(體感覺皮質)**, and parts of the **parietal-lobe association cortex**.

### Subcortical and Brainstem nuclei
- Subcortical and brainsetm nuclei are also important in learing skilled movements.
- Prominent among the subcortical nuclei are the **paired basal nuclei**, which consist of closely related group of separate nuclei.

### Parkinson's Disease (帕金森氏症)
:::danger
- the **input** to the **basal nuclei (基底核)** is **diminshed**(減少), the interplay of the **facilitatory and inhibitory circuits** is **unbalanced**, and **activation** of the **motor cortex is reduced**.
- Parkinson's disease is chararcterized by **reduced amount of movement(akinesia), slow movements(bradykinesia), muscular rigidity, and a tremor at rest**
- a major part of the initial defect arises in neurons of the **substantia nigra** These neurons normally project to the basal nucleim where they release **dopamine** from therr axon terminals.
- The **substatia nigra neurons degenerate** in Parkinson's disease, and **amount of dopamine they deliver to the basal nuclei is decreased**. This decreased the subsequent activation of the sensorimotor cortex.
- may have a **genetic cause**, and exposure to enviremoental toxins such as **manganes**, **carbon monoxide**, and **some pesticides**
- The **drugs** used to treat Parkinson's disease are all **designed to restore dopamine activity in the basal nuclei**. The fall into there categories
- agonists (stimulators) of dopamie receptros
- inhibitors of the enzymes that metabolize dopamine at synapes
- precursors of dopamine ifself (exmaple- **Levodopa**, also known as **L-dopa**)
:::

### Cerebellum
- The cerebellumn influences posture and movement indirectly by means of input to **brainstem nuclei** and (by way of the thalamus) to regions of sensorimotor cortex that give rise to pathways that descend to motror neurons
- The cerebellum **receives** information from the sensormotor cortex and also from **vestibular system**, eyes, skin, muscles, joints, and tendons.
- provide to timing signals to the cerebral cortex and spinal cord for precise execution of the different phases of a motor program, inparticula the timing of the agonist/antagonist components of a movement. It also **helps** **coordinate movements** and is **involved** in **"muscle memory"**

### Descending Pathways
The pathways are of two types:
- the **corticospinal pathways**, which, as their name implies, originate in the cerebral cortex;
- **brainstem pathways**, which originate in the brainstem.

### Corticospinal Pathway(皮質脊隨路徑)
- The nerve fibers of the corticospinal pathways have their cell bodies in the **sensorimotor cortex** and **termanate in the spinal cord**
- The corticospinal pathways are also called the **pyramidal tracts(錐體路徑)** or **pyramidal system(錐體系統)** because of their triangular shape as they **pass along the ventral surface of the medulla oblongata**

### Brainstem Pathways(腦幹路徑)
- These pathways are sometimes reffered to as the extrapyramidal system.
- **involved** with coordination of the l**arge muscle groups of the trunk and proximal portions** of the limbs used in the mainienance of upright posture, in locomotion, and in head and body movements when turning toward a specific stimulus.

### Muscle Tone (肌肉張力)
- is the resistance to stretch exhibited by a relaxed muschle

### Abnormal Muscle Tone
- Abnormally high muscle tone is called hypertonia(肌肉張力過高)
- hypertonia is accompanied by either **spasticity**, in which the excess tone diminishes as the muscles are stretched, or **rigidity**, in which the excess tone is constant
- Abnormally low muscle tone is called **hypotonia(肌肉張力過低)**, and it is due to **disorders of alpha motor neurons**, neuromuscular junctions, or the muscles themselves.
- Hypotonia is accompanied by weakness and atrophy(萎縮)

### Amyotrophic Lateral Sclerosis
- is a lower motor neuron condition in which progressive degeneration of alpha motor neuron cause hypotonai and atrophy of skeletal muscles
- In most cases that causes are not known, but may include **viruses, neurotoxin, heavy metals, immune system abnormalities, or enzyme abnormalities.**

## CH9
### Muscle classified
- Skeletal muscle 骨骼肌
- Smooth muscle 平滑肌
- Cardiac muscle 心肌
> Each type of muscle has specific characteristics and functions

### Characteristics of a Skeletal Muscle Fiber
:::danger
A skeletal muscle cell ("muscle fiber") has several defining characteristics:
- It is **multi-nucleated**
- It contains **many mitochondria**
- It has special structures called **transvers tubles (T-tubles)**
- It has **myofibrils and sarcomeres**
- It has specific terms for some structures:
- Sarcolemma = Plasma membrane
- Sarcoplasm = Cytoplasm
- Sarcoplasm reticulum = Smooth endoplasmic returculum
:::

### Myofibrils 肌纖維
Thin and thick filaments are arranged in cylindrical(圓柱) bundls called myofibrils.
- Myofibrils are structures that give **skeletal and cardiac** muscle their characteristic **striated appearance.**
> The striations result from the orderly arrangements of thick and thin filaments.

### Protein Composition of Thick filaments
- The thick filaments is composed mainly of the protein **myosin**(肌球蛋白).
- The myosin molecule is composed of two large polypeptide heavy chains.
- At th end of the heavy chains, two globular heads extend out to the sides, forming <span style="color:red;">**cross-bridges**</span>.

### Proten Compostion of thin filaments
- The **thin filaments** are principally composed of the protein <span style="color:red;">**actin**.</span>
- Two proteins **troponin** and **tropomyosin** that have important functions in regulating contraction

### Sarcoplasmic Reticlulum
- The sarcoplasmic reticulum (SR). **Ca2+ is stored** and is release following membrane excitation.
- The **T-tubules and SR** are connected with junctions
- <span style="color:red;">The T-tubule protein is a modified voltage-sensitive Ca2+ channel known as the **dihydropyridine receptors(DHP,二氫砒碇接受器)**</span>
- The protein embedded in the SR membrane is known as the **ryanodine receptor(蘭安定接受器)**,whic **forms a Ca2+ channel**
- The presence of the **Ca2+** binding protein **calsequestrin**

### The Neuromuscular junction (神經肌內接合器)
- The neuros whose axons innvervate skeletal muscle fibers are known as **alpha motor neuroms (or simply as motor neurons)** and their cell bodies are located in the <span style="color:red;">**brainstem and the spinal cord**</span>

### The Neuromuscular Junction(神經肌內接合器)(2)
:::danger
The vesicles contain the neurotransmitter <span style="color:red">**acetylcholine (ACh)**.</span>

- **All neuromuscular junctions are excitatory.**
- the synaptic junction contains the enzyme **acetylcholinesterase**, which **breaks down ACh**
:::

### Disruption of Neuromuscular Signaling
The antidote(解藥) for organophosphate and nerve gas exposure includes both **pralidoxime(磷定)** which **reactivates acetylcholinesterase,** and **the muscarinic receptor antagonist atropine(阿托品)**
:::danger
Drugs that block neuromuscular transmission are sometimes **used in small amounts to prevent muscular contractions** during certain types of surgical procedures.
肌肉鬆弛劑
One example is **succinylcholine(琥珀膽鹼)**, which actually acts as an agonist to the ACh receptors and produces a **depolarizing/desensitizing block similar to acetylcholinesterase inhibitors.**

**Nondepolarizing neuromuscular junction blocking drugs** that act more like curare and last longer are also used, such as **rocuronium (羅庫溴銨)** and **vecuronium(維庫溴銨)**.
:::

### Disruption of Neuromuscular Signaling (4)
The toxin produced by the bacterium **Clostridium botulinum(肉毒桿菌)**,**blocks the release of acetylcholine from axon terminals**
### !!!Sliding of thick filaments past overlapping thin filaments shortens the sarcomere with no change in thick or thin filament length
:::danger

收縮時哪一個不會變短，哪個會變短

- A band (紅色)不會變短
- H zone變短
- Sarcomere 變短
- I band變短
:::

### !!!Skeletal Muscle Energy Metabolism
:::danger
As we have seen ATP performs four functions directly related to muscle fiber contraction and relaxtion.

There are theree ways a muscle fiber can form ATP:
- phosphorylation of ADP by **creatine phosphate**
- oxidative phosphorylation of ADP in the mitochondria
- phosphorylation of ADP by the glycolytic pathway in the cytosol
:::

### Muscle Fatigue (肌肉疲勞)
This decline(衰退) in muscle tension as a result of previous contractile activity is known as **muscle fatigue**.

### Types of Skeletal Muscle Fibers
- Slow-oxidative fibers(type 1) combine low myosin-ATPase activity with high oxidative capacity.
- Fast-oxidative-glycolytic fibers(type 2A) combine high myosin-ATPase activiy with high oxidative capacity and intermediate glycolytic capacity.
- Fast-glycolytic fibers(type 2X) combine high myosin-ATPase activity with high glycolytic capacity.

### Control of Muscle Tension
The total tension a muscle can develop depends upon two factors:
- The amount of tension developed by each fiber
- the number of fibers contracting at any time

### !!!Factors Determining Muscle tension
:::danger
Tension developed by each fiber
- Action potential frequency (frequency-tension relation)
- fiber length(length-tension relation)
- fiber diameter(直徑)
- fiber type
- fatigue

Number of active fibers
- Number of fibers per motor unit
- Number of active motor units
:::

### Muscle Adaptation to Exercise
"Use it or lose it."" Muscles that are not used will atrophy(萎縮).
There are 2 types of atrophy:
- Disuse atrophy (like an arm in a cast)
- Denervation atrophy(nerve damage= loss of function)

### Skeletal Muscle Disorders
- **poliomyelitis**(小兒麻痺症) is a viral(病毒) disease that can **destroy motor neurons** leading to the **paralysis of skeletal muscle**

### Muscle Cramps
- Involuntary tetanic contraction of skeletal muscles produces muscle cramps
- During cramping, **action potentials fire at abnormally high rates**
- The specific cause of this high activity is uncertain, but it may be partly related to **electrolyte imbalances**
- These imbalances may arise from **overexercise or persistent(持續) dehydration(脫水)**

### Muscular Dystrophy(肌肉萎縮症)
It is associated with the progressive degeneration of skeletal and cardiac muscle fibers, weakening the muscles and leading ultimately to death from respiratory or cardiac failure.
- **Costameres (肋狀肌)** are clusters of structural and regulatory proteins that link the disk of the outermost myofibrils to the sarcolemma and extracellular matrix
- <span style="color:red;">**Duchenne muscular dystrophy(杜氏肌肉萎縮症)**</span> is a **sex-linked recessive disorder** caused by a defect in a gene on the **X chromosome** that codes for the protein, dystrophin.
> 母親的X染色體其中一條有缺陷所造成的，因此母親完全沒有病徵，是隱性帶因，若生下男嬰，而且自母親遺傳到帶有缺陷的染色體，就會成為此症的受害者

### Myasthenia gravis (重肌症無力)
- A number of approaches are currently used to treat the disease. One is to administer acetylcholinesterase inhibitors (for example, **pyridostygmine**).
- **Plasmapheresis** is a treatment that involves replacing the liquid fraction of blood (plasma) that contains the offending antibodies.

### Structure of smooth muscle
- have a <span style="color:red;">**single nucleus**</span>
- They have thick myosin-containing filaments, thin actin-containing filaments, and tropomyosin, but they <span style="color:red;">**do not have troponin.**</span>
- The thin filaments are anchored either to the plasma membrane or to cyoplasmic structures known as **dense bodies(緻密體)**
- NO sarcomeres(肌節)
- contraction occurs by a **sliding-filament mechanism.**

### !!!Smooth Muscle Contraction and its Control
:::danger
Cross-Bridge Activation
- Cross-bridge cycling in smooth muscle is controlled by **Ca2+ regulated enzyme** that phosphorylates myosin
- This is done by myosin light-chain kinase(MLCK)
- To **relax a contracted smooth muscle**, myosin **must be dephosphorylated** because dephosphorylated myosin is unable to bind to actin. This dephosphorylation is mediated by **the enzyme myosin light-chain phosphatase**
:::

### *Cross-bridge activation (smooth muscle v.s skeletal muscle)

### Spontaneous Electrical activity
- Some type of smooth muscle cell **generate action potentials spontaneously** in the absence of any neural or hormonal input.
- The membrane potential change occurring during the spontaneous depolarization to threshold is known as a **pacemaker potential**
- The membrane potential drifts up and down due to regular variation in ion flux across the membrane. **These periodic fluctuations are called slow waves**
- Pacemaker cells are found throughout the gastrointestinal tract(胃腸道)

### !!!Nerves and Hormones
:::danger
- The contractile activity of smooth muscles is influenced by neurotransmitters release by autonomic neuron endings.
- <span style="color:red;">Innervating autonomic neurons have swollen regions know as **varicosities**</span>
- Each varicosity contains many vesicles filled with neurotransmitter, some of which are released when an action potential passes the varicosity
:::

### Nerves and Hormones (2)
- epinephrine enhances contraction of most vascular smooth muscle by acting on **α1- adrenergic receptors**
- relaxation of airway (bronchiolar) smooth muscle by acting on **β-2 adrenergic receptors**

### Types of Smooth muscle
- **Single-unit smooth muscle** respond to stimuli as a single unit because cells are connected by **gap junctions**
- **Multiunit smooth muscles** contain cells that respond to stimuli independently, and they contain **few gap junctions**

### !!!Cardiac Muscle
:::danger
- Cardiac muscle cells have **one to two nuclei** that are centrally located
- The are **striated** and use the **sliding-filament mechanism** to contract
- (**這點比較重要**)They are <span style="color:red;"> **branched cells** with **intercalated disks(間盤)**</span> at ther ends, which contain <span style="color:red;">**desmosomes(胞橋體, 重點) and gap junction**</span>
- The nodal cells have ability to stimulate their own action potentials. This is called **automaticity or autorhythmicity.**
:::

### Characteristics of Muscle cells

## CH11

### Hormone Structures and Synthesis
:::danger
Hormones fall into three major structural classes:
- Amines 胺類
- Peptides and proteins (胜肽類)
- Steroids 固醇類
:::

### The five Hormnes shown in boxes are major hormines secreted from the adrenal cortex
:::danger
Cholesterol(膽固醇) 為其中的原料
:::

### Gonadal Production of Steroids
:::warning
:::

### Hormone Transport in the blood
- **Most peptide and all catecholamine hormones are water soluble**
- **poorly soluble steroid hormones and thyroid hormones circulate in the blood largely bound to plasma proteins**

### Hormone receptors
- An increase in the number of receptors for a hormone is call **up-regulation**
- A decrease in the number of receptors for a hormone is called **down-regulation**

### Example of how the direct control of hormone secretion by the plasma concentration of a substance result in negative feedback control of substance's plasma concentration

### Control by other hormones
- A hormone that controls the secretion of another hormone is often referred to as a **tropic hormone**

### Types of Endocrine disorders
- **Hyposecretion** : the secretion of too little hormone
- **Hypersecretion**: the secretion of too much hormone
- Hyporesponsiveness: decrease responsiveness of the target cells to hormone
- Hyperresonponsiveness: increase responsiveness of the target cells to hormone

### !!!The Hypothalamus and Pituitary Gland
Rule out排除
:::danger
**Pituitary腦下垂體**
**從視上送到 posterior 再送到 Abterior**
:::

### !!!Posterior Pituitary Hormones
:::danger
- The posterior pituitary does **"not"** synthesize its two hormones;it only secretes them
- **Oxytocin** is involved in the **milk ejection reflex of nursing mothers and emotional bonding**
- **Antidiuretic hormone(vasopressin加壓素)** is involved in **blood vessel constriction and in regulation of water balance and osmolarity**
:::

### Anterior Pituitary Hormones and the Hypothalamus
:::danger

只有一個inhibits Somatostatin
:::

### Actions of Thyroid hormones
Metabolic Actions:
- **T3 stimulates carbohydrate absorption from the small intestine(小腸) and increases fatty acid releases from adipocytes**
- **ATP is consumed in cells by Na+/K+ ATPases at a high rate due to T3 stimulation**, and thus the cellular stores of ATP must be maintained by **increased metabolism of fuels**

Permissive Actions:
- Some of the action of T3 are attributable to its premissive effects on the actions of catecholamines
- **T3 up-regulates beta-adrenergic receptors in many tissues, notably the heart and nervous system.**

Effect of Growth and Development:
- **T3 is required for normal production of growth hormone from the anterior pituitary gland**

### The Endocrine response to stress
- **Stress**, in its broadest meaning, is a real or perceived threat to homeostasis.
- The endocrine system responds to stress by **increasing the release of cortisol from the adrenal cortex** and **epinephrine from the adrenal medulla**

### Physiological functions of Cortisol(皮質醇)
- **Permits action of epinephrine and norepinephrine on smooth muscle cells** surrounding blood vessels, thereby helping to **control blood pressure**
- Maintains cellular concetrations of metabolic enzymes required to **produce glucoese** between meals, thereby helping to prevent low blood glucose concentrations. This is the reason **cortisol is referred to as a glucocorticoid**
- **Decrease event** associated with the **inflammatory response** such as capillary permeability and production of **prostaglandins.(前列腺素)**

### Adrenal Insufficiency
- Any stuation in which plasms levels of cortisol are chronically lower than normal
- symptoms: weakness, fatigue, and loss of appetite and weight
- Examniation may reveal **low blood pressure**(in part because cortisol is nedded to permit the full extent of the cardiocvascular action)and **low blood sugar** (especially after fasting, because of the loss of tthe normal matabolic actions of cortisol)

:::danger
- **Primary adrenal insufficiency** is due to a loss of adrenocortical function, as may rarely occur, for example, when infectious(傳染性) diseases such as tuberculosis(結核病) infiltrate(潛入) the adrenal glands and destroy them
- Most commonly by far, however, the syndrome(症候群) is due to <span style="color:red;">**autoimmune attack**</span> causing the destruction of many of the cells of the adrenal glands
:::

- The loss of salt and water balance may lead to hypotension(low blood pressure)
- Primary adrenal insufficiency from any of these cause is also known as **Addison's disease**

### Cushing's Syndrome
- There is **excess(過量的) cortisol in the blood**, even in the nonstressed individual
- The cause may be a primary defect(for exmaple, a **cortisol-secreting tumor of the adrenal**) or may be secondary(usally due to an **ACTH-sereting tumor of the anterior pituitary gland**)
- In secondary the increased blood levels of cortisol tend to promote uncotrolled catabolism of bone, muscle, skin and other organs

### Cushing problem
- Osteoporosis
- Muscles weakness
- Thin, easily bruised skin
- blood sugar increases to levels observed in diabetes mellitus
- immunosuppression
- Redistribution of fat (buffalo hump and moon face)
- Hypertension (high blood pressure)
Treatment:
- Surgical removal of the pituitary tumor
- Adrenalectomy

### Other homrmones release dring stress
- Vasopressin and aldostreon act to retain water Na+ within the body, an important response in the face of potential losses by dehydration, hemorrhage(出血), or sweating
- The overall effects of the changes in **growth hormone, glucagon**, and insulin are, like those of cortisol and epinephrine to mobilize energy stores and increase the plasma concentration of glucose
- The fight-or-flight response also causes an increase in the secretion of epinephrine and norepinephrine

### Hormonal influences on growth
:::danger
- Growth hormone
- Insulin-like growth factors 1 and 2
- T3
- Insulin
- Sex hormones (testosterone, estradiol)
- Cortisol
:::

### Major Effects and Growth hormone
- **Promotes growth**: Induces precursor cells in bont and other tissues to differentiate and secrete insulin-like growth factor 1(IGF-1), which stimulates cell division. Also stimuldates liver to secrete IGF-1.

### Effector sites for Ca2+ Homeostasis
:::warning
Calcium storage, absorption into the body, and excretion from the body occur at 3 main sites:
- Bone
- Kidneys
- Gastrointestinal tract
:::

### !!!Summary of major hormonal influences on Bone mass
- Osteoblasts 成骨細胞
- Osteoclast 蝕骨細胞
- Osteocyte 骨細胞
:::danger
Hormones That favor bone formation and increase bone mass:
- Insulin
- Growth hormone
- Insulie-like growth factor 1 (IGF-1)
- Estrogen
- testosterone
- calcitonin

Hormones that favor increased bone resorption and decreased bone mass
- Parathyroid hormone (chronic increases)
- Cortisol
- Thyroid hormone T3
:::

### Hormonal Controls
:::warning
Two major hormones regulate plasma calcium concentration:
- Parathyroid hormone
- 1,25-dyhydroxyvitamin D
A third hormone, calcitonin, has a very limited function human, if any.
:::

### Parathyroid Hormone (副甲狀腺)
- **Parathyroid hormone (PTH)** is produced by the **parathyroid glands**.
- **PTH is critically important to regulation of calcium levels**

### Calcitonin
- Calctonin is a peptide hormone secreted by cells called parafolicular cells that are whthin the thyroid gland but are distinct from the thyroid follicles
- Calctonin decrease plasma calcium concentration, mainly by inhibiting **oseoclasts**

### Metablolic bone disease
:::danger
- **Rickets (佝僂病 in children)** and **osteomalacia(軟骨病 in adult)** are condition in which mineralization of bone matrix is deficient, causing the bones to be soft and easily fractured. **A major cause of rickets and osteomalacia is <span style="color:red;">deficiency of vitamin D</span>**

- **Osteoporosis** (骨質疏鬆) is an imbalance between bone resorption and bone formation resulting in decreases in bone mass and strength. It leads to an increased fragility(脆弱性) of bone and the incidence of fractures
- Osteoporosis is most commonly seen with <span style="color:red;">**aging**</span>
- Everyone loses bone with age, but osteoporosis is more common in elderly women than men. The major reason fo this is that menopause(更年期) removes the antiresorptive effect of estrogen.

:::

### Treatment options for osteoporosis
- regular weight-bearing exercise program
- adequate(充分) dietarty(飲食) **Ca2+ and vitamin D intake**
- drugs called **bisphosphonates**, that interfere with the resorption of bone by osteoclasts
- other antiresorptive substances include calcitonin and **selective estrogen receptor modulators(SERMs)** which act by interacting with estrogen receptors, thereby compensating for the low estrogen after menopause.

### Hypercalcemia(高血鈣)
- Cause of hypercalcemia (abnormally high levels of ca2+ in the blood)
- **primary hyperparathyroidism** cause by benign(良性) tumor in one of the four parathyroid glands
- certain types of cancer that can lead to **humoral hypercalcemia of malignancy(惡性腫瘤)**
- excessive ingestion of vitamin D
:::warning
symptoms includes:
- tiredness
- lethargy with muscle weakness
- nausea and vomiting (due to effects on the GI tract)
:::

### Hypocalcemia(低血鈣)
- **primary hypoparathyroidism**, which is loss of parathyroid gland function
- **pseudohypoparathyroidism** which is resistance to the effects of PTH in target tissue, even though PTH levels in the blood tend to be elevated
- **secondary hyperparathyroidism**, which is **failure to absorb vitamin D from the intestines**, or decreased kidney 1,25 - (OH)2 D production which can occur in kidney disease