Third term - HackMD

###### tags: `生理學` # Third term ## 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 ![](https://i.imgur.com/aKiufoo.png) - Dehydroepiandrosterone - Androstenedione - Cortisol - Corticosterone - Aldosterone ::: ### Gonadal Production of Steroids :::warning ![](https://i.imgur.com/kL1iUO4.png) ::: ### Hormone Transport in the blood - **Most peptide and all catecholamine hormones are water soluble** - in contrast, **poorly soluble steroid hormones and thyroid hormones circulate in the blood largely bound to plasma proteins** - only free hormones interact with target cells ### 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 ![](https://i.imgur.com/CGHYwfB.png) ### 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** ![](https://i.imgur.com/lEKVvKY.png) **從視上送到 posterior 再送到 Anterior** Supraoptic nuclei=> posterior pituitary ::: ### !!!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 ![](https://i.imgur.com/WUu27rO.png) 只有一個inhibits Somatostatin ::: ### Summary of the hypothalamic-Anterior Pituitary Gland System - Anterior Pituitary Homones and the Hypothalamus to target organs ![](https://i.imgur.com/IUbHSKd.png) > - Luteinizing hormone，LH > - Follicle-Stimulating Hormone，FSH ### Actions of Thyroid hormones :::danger 這題有考 Thyroid分泌過多的病: Goiter ::: 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 situation in which plasms levels of cortisol are chronically lower than normal - symptoms: weakness, fatigue, and loss of appetite and weight - Examination 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 **autoimmune attack** 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 Hormones Released During 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 bone 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(蝕骨)** ### Metablolic bone disease :::danger - (這題有考)**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 deficiency of vitamin D** - **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 **aging** - 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 # CH12 ## Circulatory system overview The **three principal** components that comprise the **circulatory system** are: - the **heart** (the pump) - the **blood vessels** or **vascular system**(set of interconnected tubes) - the **blood** (a fluid connective tissue containing water, solutes, and cells that fills the tubes) **Cardiovascular system(心臟血管系統)** function is impacted by the endocrine, nervous, and urunary systems(泌尿系統) ## Measurement of the hematocrit by centrifugation - Blood is composed of **formed elements** (cells and cell fragments) suspended in a liquid called **plasma** Plasma: 55% Erythrocytes(hematocrit): 45% ## Plasma - Plasma consists of a large number of inorganic and organic substances dissolved in water. **Most(>90%) of plasma is water.** - Plasma carries plasma proteins such as **albumins(白蛋白), globulins(球蛋白), and fibrinogen(纖維蛋白原)** - **Serum** is plasma with fibrinogen and other proteins involved in clotting removed ## Erythrocytes (Red blood cells) :::danger - The major function of erythrocytes is **gas transport**;**they carry oxygen taken in by the lungs and carbon dioxide produced by the cells** - Erythrocytes contain large amounts of the protein **hemoglobin** to which oxygen and carbon dioxide reversibly combine. - Mature erythrocytes **do not have a nucleus nor organelles (no mitochondria, no DNA, no RNA) so no division of mature RBCS** ::: :::danger - (**這題有考**)erythrocytes have a short life span and only last **120 days** - (**這題有考**)they are synthesized in **red bone marrow** by a preocess called **erythropoiesis.** ::: - **Erythropoietin(紅血球生成素)**(a hormone from the kidney) triggers differentiation of stem cells to erythrocytes ## Filtering and Destruction of Erythrocytes :::danger - (**這題有考**)**The spleen filters and removes old erythrocytes, and the liver metabolizes byproducts from breakdown of erythrocytes** - Most of the **iron** is conserved for the synthesis of new hemoglobin ::: - Iron is transported in blood bound to an iron-transport plasma protein called **transferrin**, which delivers almost all of it **to the bone marrow** to be **incorporated into new erythrocytes** - Iron is stored bound to a protein called **ferritin** in the **liver, spleen and small intestines** ## requirements for normal erythrocytes production :::danger 這題有考 - **Iron** - Component of hemoglobin (specfically the heme protion to which oxygen binds) - **Folic acid** - Essential for the formation of DNA and normal cell division - **Vitamin B12** - Required for the action of folic acid ::: ## Erythropoietin and Clinical Issues - **Renal dialysis patients** whose kidneys have failed **have too little** erythropoietin and need to have synthetic forms administered to maintain normal RBC counts - **Athletes** who abuse this synthetic form (to increase stamina) can have problem with the blood becoming **too viscous**, which could result in clotting, stroke, and heart failure - **Testosterone** enhances RBC production by increasing erythropoietin production (**hence men have higher hematocrit than women**) so people on hormone replacement need to be very careful with dosing ## Anemia(貧血) - **Anemia** is a decrease in the oxygen-carring capacity of blood due to - a decrease in the total number of erythorcytes - a diminished concentration of hemoglobin - a combination of both **Sickle-cell disease** (also called sickle-cell anemia) is due to a genetic mutation that alters one amino acid in the hemoglobin chain ## Major causes of Anemia :::danger - Dietary deficiencies of iron (iron-deficiency anemia), vitamin B12, or folic acid - Bone marrow failure due to toxic drug or cancer - Blood loss from the body (hemorrhage) - Inadequate secretion of erythropoietin in kidney disease - Excessive destruction of erythrocytes(for example, sickel-cell disease) all of above ::: ## Leukocytes(白血球) :::danger Leukocytes (white blood cells) are involved in immune defenses **考哪一個是agranulocytes** divided into granulocytes and agranulocytes - **Granulocytes (顆粒球)** contain cytoplasmic granules - Neutrophils - Eosinophils - Basophils - **Agranulocytes (非顆粒球)** do not contain cytoplasmic granules - Monocytes - Lymphocytes - Marophages ::: ## Leukocyte basic functions :::danger - (**有考這個**)**Neutrophils** are phagocytes, and their production and release from the bone marrow increase during **infections**. - **Eosinophils** fight off invasions by eukaryotic parasites; their granules contain toxic molecules that attack **parasites**(寄生蟲) or they are capable of phagocytosis - **Basophils** secrete an anticlotting factor called heparin at the site of infection, which help the circulation flush out the infected site; they also **secrete histamine** to attract infection-fighting cells and proteins to the site - **Monocytes** are **phagocytes** that circulate in the blood for a short time, after which they migrate into tissues and organs and develop into **macrophages** - **Macrophages** are large **phagocytes capable of engulfing viruses and bacteria** - **Lymphocytes** are compised of **T-and B-lymphocytes** that protect against specific pathogens, including viruses, bacteria, toxins, and cancer cells. ::: ## Platelets (血小板) Platelets are produced when cytoplasmic portions of large bone marrow cells, termed **megakaryocyte** pinch off and enter the circulation ## The systemic and pulmonary circulations - **Pulmonary circulation** carries oxygen-poor blood from the right ventricle(右心室) to the lungs(肺) and then to left atrium(左心房) - **Systemic circulation** carries oxygen-rich blood from the left ventricle through all the organs and tissues of the body- except the lungs and then to the right atrium ## blood vessels (血管) - blood vessels can be divied into **artries(動脈), arterioles(小動脈), capillaries(微血管), venules(小靜脈), and veins(靜脈)** - All arteries carry blood away from the heart, whereas all veins carry blood to the heart :::danger - In general, arteries carry oxygenated blood, and vesins carry deoxygenated blood - The **exception** to this is the **pulmonary arteries, which carry deoxygenated blood to the lungs to get oxygenated**, and the **pulmonary veins, which carry oxygenated blood** to the heart to get delivered to the rest of body ::: ## Presure, flow, and resistance 略看就好 - **Pressure** is the force exerted by the blood and is measured in **mmHg** (millimeters of mercury) - **Flow** is the volume move per unit time, and it is measured in milliter/minute - **Resistance** descibes how difficult it is for blood to flow between to points at any given pressuredifferenec. Resistences is the measure of the friction that impeds flow - if you increase the resistance, you decrease flow if presure stays the same ## Resistance 略看 - Blood viscosity(黏性), which is a function of the friction between molecules of a flowing fluid - Total blood vessel length - inside radiu of the tube ## Heart layers - **Epicardium(心外膜)**: this is the most superficial(outer) layer. It is fibrous layer that is closely affixed to the heart - **Myocardium(心肌)**: This is the middle layer of the heart muscle. It is composed of cardiac muscle and forms the bulk of the heart mass - **Endothelium (內心膜)**: This is the inner layer of the heart composed of **endothelial cells**, or **endothelium(內皮)**, which rest on a thin layer of connective tissue. It is continuous with the lining of the blood vessels entering and leaving the heart ## Cardiac Muscle (心肌) 略看 - The cardiac muscle cells of the myocardium are arranged in layers that are tightly bound together and completely encircle the blood-filled chambers 略看 - When the walls of a chamber contrat, they comes together like a first squeezing a fluid-filled ballon and exert pressure on the blood they enclose. - Every heart cell contracts with every beat of the heart; cardiac muscle cells may contract **alomost 3 billion times in an average life span** without resting. - The human heart has limited ability to replace its muscle cells. Recent expreiments suggest that only about 1% of heart muscle cells are replaced pre year. ## Cardiac communication - Approximately **1%** of **cardiac cells do not** function in **contraction** **but** have specialized features that are **essential for normal heart excitation** - These cell constitute a network known as the **conducting system** of the heart and are in electrical contact with the cardiac muscle cells via **gap junctions**. - The **conducting system initiates the heartbeat and helps spread an action potenial rapidly** throught the heart ## Innervation (支配) of the heart - The heart receives a rich supply of **sympathetic(SNS) and parasympathetic(PSNS)** - The **sympathetic** postganglionic fibers innervate the entire heart and **release norepinephrine**, whereas the **parasympathetic** fibers terminate mainly on special cells found in the atria and release primarily **acetylcholine** - The **receptors for norepinephrine** on cardiac muscle are mainly **beta-adrenergic**. The hormone **epinephrine**, **from** the **adrenal medulla**, binds to the same receptors as norepinephrine and exerts the same actions on the heart - **The receptors for acetylcholine are the muscarinic type** :::danger ![](https://i.imgur.com/9OPr4uq.png) ::: ## Blood supply - The **blood** being **pumped** through the **heart chambers does not exchange** **nutrients(營養素)** and **metabolic end products** with the **myocardial cells** - They receive their blood supply via arteries that **branch from the aorta**. - The arteries supplying the myocardium are the **coronary arteries**, and the blood flowing through them is the **coronary blood flow** - **coronary arteries** **exit from behind the aortic valve cusps(主動脈瓣膜) in the very first part of the aorta** and lead to **branching network** of small arteries, arteriole, capillaries, venules, and veins similar to those in other organs. :::danger **這題有考** - Most of the cardiac veins drain into single large vein the **coronary sinus**, which empties into the **right atrium** ::: ## Excitation of the heart :::danger **這題有考** ![](https://i.imgur.com/sLcoQCl.png) 1,2,3,4,5步驟 - Sinoatrial node (SA) - Atrioventricular node - Bundle of His - Left and right bundle branch - Purkinje fibers ::: - The **sinoatrial (SA) node** is **normally the pacemaker** for the **entire heart**. the **action potential initiated** in the SA node **spreads throughout the myocardium**, **passing from** cell to cell by way of **gap junctions** - **Depolarization first spreads through** the muscle cells of the **atria**, with **conduction rapid enough** that the **right and left atria contract** at essentially the **same time**. - The action potential is conducted relatively rapidly from the **SA node to** the **atrioventricular (AV) node** through **internodal pathways** - Then, the wave of depolarization travels down the **interventricular septum**(室間格) through conducting-system fibers called the **bundle of His** - Within the interventricular septum, **the bundle of His divides into** **right and left bundle branches**, which separate at the bottom(apex) of the heart and enter the walls of both ventricles - These pathways are composed of **Purkinje fibers**, which are large diameter, rapidly conducting cells connected by low-resistance gap junctions ## Nodal cells - The **SA node cell** does not have a steady resting potential but, instead, undergoes a slow depolarization. - This gradual depolarization is known as a **pacemaker potential**; It brings the membrane potential to threshold, at which point an action potantial occurs - Thus, the pacemaker potential provides the SA node with **automaticity**, the capacity for spontaneous, rhythmic self-excitation ## Counduction Disorders - **Drug or disease induced** malfunction of the **AV node** may **reduce** or completely eliminate the transmission of action potentials from the atria to the ventricles. This is known as an **AV conduction disorder**. - If this occur, autorhythmic cells in the **bundle of His** and **Purkinje network, no longer driven by SA node**, begin to initiate excitation at their own inherent rate (25 to 40 beats/minute) and become the pacemaker for the ventricles - treatment: artificial pacemaker ## Electrocardiogram (心電圖) - The electrocardiogram(ECG) is a tool for evaluating the electical events within the heart. - A typical ECG makes use of **multiple** combiantions of recording **locations** on the **limbs and chest**(callde **ECG leads**) so as to obtain as **much information** as possible **concerning different areas** of the heart :::warning ![](https://i.imgur.com/uY8KmZP.png) - The **P wave** corresponds to current flow **during atrial depolarization** - (**這題有考**)The **QRS complex** is the result of the **ventricular(心室) depolarization** - The **T wave** is the result of **ventricular repolarizaiton** ::: - **Atrial repolarization** is **usually not evident(明顯的) on the ECG** because it occurs at the same time as the QRS complex ## Excitation-Contraction Coupling - A **small amount of extracellular calcium** the cell **through L-type calcium channels** during the **plateau of the aciton potential**. - This **calcium binds to ryanodine receptors** on the sarcoplasmic reticulum membrane and triggers the release of a larger quantity of calcium ## Cardiac Cycle - The orderly process depolarization triggers a recurring **cardiac cycle** of atrial and ventricular **contractions** and **relaxations** - The cycle is divide into two major phases, both named for events in the ventricles:the period of ventricular contraction and blood ejection called **systole(收縮)**, and the alternating period of ventricular relaxation and blood filling, **diastole(舒張)** - For a typical heart rate **of 72 beats/minutes**, each cardiac cycle lasts approximately **0.8 seconds, with 0.3 seconds in systole and 0.5 seconds in diastole** ## Clinical Applications - The first sound, a soft, low pitched **lub**, is associated with **closure of the AV valves**; the second sound, a louder **dup**, is associated with **closure of the pulmonary and aortic valves** - These sounds, which result from vibrations caused by the closing valves, are normal, but other sounds, known as **heart murmur(心雜音)**, can be a sign of heart disease - Normaly, blood flow through valves and vessels is **laminar flow**-that is, it flow in smooth conecntric layer. - Turbulet flow can be caused: - blood flowing through an abnormally narrowed valve (**stenosis**) - blood flowing backward through a damaged, leaky valve (**insufficiency**); - blood flowing between the two atria or two ventricles through a small hole in the wall separating them (called **a septal defect**) ## Cardiac Output - **Cardiac Output** is the volume of blood pumped out of each ventricle per unit time - it is the product of **heart rate (HR)** and **stroke volume (SV)** ## Regulation of heart rate - SA node is normally under constant influence of **nerves and hormones** - Activity in **parasympathetic neurons** causes the heart rate to **decrease**, whereas activity in the **sympathetic** neurons cause an **increase**. These are termed **chronotropic effects** ## Stroke Volume - Stroke volume (SV) is the volume of blood each ventricle ejects during each contraction. Three factors dominate SV under most physiological and pathophysilocical conditions: - Changes in the end-diastolic volume(the volume of blood in the ventricles just before contraction, sometimes referred to as the **preload(前負荷)**) - Changes in the magnitude of sympathetic nervous system input to the ventricles - Changes in **afterload(後負荷)** (that is , the arterial pressures against which the ventricles pump) ## Effects of autonomic nerves on the heart ![](https://i.imgur.com/BwG4kB3.png) ## Measurement of Cardiac function - **Echocardiography(心臟超音波)** is a noninvasive(無創) technique that use ultrasonic waves. This can detect the abnormal functioning of cardiac valves or contractions of the cardiac walls, and it can also be used to measure ejection fraction - **Cardiac angiography(心臟血管攝影)**: requires the temporary threading of a thin, flexible tube called a **catheter** through an artery or vein into the heart. A liquid containing radiopaque(不透光) contrast material is then injected through the catheter during high-speed x-ray videography. this technique is useful for evaluating cardiac function ## The vascular(血管) system - The vascular system has a **major function** in **regulating blood pressure** and distribuing **blood flow to various tissue**. - The entire cirulatory system, from the heart to the smallest capillary, has one structural component in common: a smooth, single-celld layer of **endothelial cells(endothelium)** that is in contact with the flowing blood. - Different vessels include: arteries, arterioles, capillaries, venules and veins ## Arteries - **Arteries** can be viewed as **elastic tubes** due to **having thick walls** containing large quantities of elastic tissue - They have **large radii**, which help them serve as low-resistance tubes conducting blood to the various organs - Arteries also act as **"pressure reservoirs"** for maintaining blood flow through the tissues during diastole ## Pulse Pressure - The difference between systolic and diastolic (120-80=40) is called pulse pressure - It can be felt as pulsation(脈動) or throb(悸動) in the arteries of the wrist or neck with each heartbeat :::warning The most important determining magnitude of the pulse pressure are: - stroke volume - speed of ejection of the stoke volume - arterial compliance a **decrease** in **arterial compliance** occurs in **arteriosclerosis**, a stiffening of the arterial walls that progresses with age ::: ## Mean arterial pressure - The **mean arterial pressure (MAP)** is approximately equal to the diastolic pressure plus one-third of the pulse pressure - The **MAP** is and **important parameter** because it is the **average pressure driving blood into tissue averaged over the entire cardiac cycle.** ## Arterioles(小動脈) Two major functions: - The arterioles in individual organs are responsible for **determining the relative blood flows** to those organs at any given **mean arterial pressure** - The arterioles, all together, are the **major factor** in **determining mean arterial pressure** itself. - Their **diameter** is **controlled by neural, hormonal, and local chemicals** ## Endothelial cells and Vascular Smooth Muscle - **Endothilial cells** secrete several paracrine agents that diffuse to the adjacent vascular smooth muscle and induce either relaxation or contraction - One of the most important is **nitric oxide(NO)** - **NO** is released continuously in significant amounts by endothelial cells in the arterioles and contributes to arteriolar **vasodilation** in the basal state - NO causes vasodilation and is critical to proper vessel tone. EX: **sildenafil(Viagra) & tadalafil(Cialis)** ## Capillaries - Capillaries are the smallest blood vessels and are comprised of a single layer of endothelial cells - they **contain 5% of the total circulating blood** - they **permeate(滲透) every tissue except the "cornea"** - **Gas and nutrient exchange** occurs between capillaries and the surrounding interstitial fluid by diffusion ## Diffusion Gradients at a systemic capillary :::danger ![](https://i.imgur.com/ee18X4Y.png) 動脈進去=>靜脈出來 From arteriole to venule 交換的地方: Capillary ::: ## Fluid movement across capillaries - The direction fluid moves at the capillaries is dependent on the difference between the **net hydrostatic pressure and the net colloid osmotic pressure** - **Hydrostatic pressure** is the force exerted by the fluid pressing against a wall. In the capillaries it is the same as the capillary blood pressure - In capilaries the **pressure tends to force fluid out (filtration)**, especialy on the arterial end where pressure is higher ## Osmotic pressure(滲透壓) - **Colloid osmotic pressure(oncotic**) is the force that opposes the hydrostatic pressure - It is created by the large **nondiffusible** molecules, like **plasma proteins** - Unlike the hydrostatic force, it does not vary form one end of the capilary to the other ## Venules and veins :::danger - Venules **have a large capacity** for blood; That is , thay are capacitance vessels. - They have some permeability to macromolecules, and they are also the site of **migration of leukocytes into tissues during inflammation and infection** - Veins also have **less smooth muscle than arteries and arterioles** - Because of their high compliance, veins are referred to as **capacitance vessels** that act as **blood reservoirs** ::: ## The lymphatic system - **lymphatic system** is network of small organs(lymph nodes) and tubes (**lymphatic vessels**) through which **lymph**- a fluid derived from intersitial fluid- flows - Small amounts of interstitial fluid continuously enter the lymphatic capillaries by bulk flow. - The lymph flows through the **lymph nodes**, which are part of the **immune system** - Eventually, the lymphatic vessels carry the interstitial fluid vack to the circulatory system. - have smooth muscle and valves ## The lymphatic system is a one-way sytstem from interstitial fluid to the circulartory system :::danger 淋巴進到體循環的地方 ![](https://i.imgur.com/urvRtjg.png) ![](https://i.imgur.com/gBAzPe4.png) - Subclavian veins ::: ## lymphatic Clinical - **Elephantiasis(象皮病)** is a Disease Resulting When Mosquito borne Filarial Worms Block the Return of Lymph to the Vascular System - Some infected lymph nodes become visible and are called **buboes**. - These are also a site where **metastasizing cancers** live and spread. This is why we biopsy them for **breast cancer** etc. Those nodes are swollen but not usually painful ## Location of **Arterial Baroreceptors(動脈壓力感受器)** :::danger **這題有考** - **Carotid sinus baroreceptor** - **Aortic arch baroreceptor** ::: ## other cardiovascular reflexes and response Blood pressure is affected by arterial concenetrationsd of oxygen and carbon dioxide, changes in blood flow to the brain, pain, sexual activity, eating, mood, and stress ## Hypotension (低血壓) - The term **hypotension** means a low blood pressure regardless of the cause. - One cause of hypotension is significant loss of blood volume, as in a **hemorrhage**. **This reduces blood flow to the brain and cardiac muscle** - Other causes include a decrease in cardiac contractility **strong emotion**, and massive release of endogenous substances that **relax arteriolar smooth muscle** as might occur during an **allergic reaction(過敏反應)** ## Shock The term **shock** denotes any situation in which a decrease in blood flow to the organs and tissues damages them. :::danger - **Hypovolemic shock** Due to **decrease in blood volume** secondary to **hemorrhage** or **loss of fluid other than blood** - **Low-resistance shock** Due to **decrease in total peripheral resistances** secondary to **excessive release of vasodilators**, as in **allergy and infection** - **Cardiogenic shock** Due to an **extreme decrease in cardiac output** from any of a variety of factors(for example, **during a heart attack**) ::: ## Hypertension (高血壓) - **Hypertension** is defined as a chronically increased systemic arterial pressure(above 140/90 millimeters hg) - Hypertension is a contributing **cause** of some of the **disability and death**. One of the organs most affected is the heart - Hypertension of **uncertain cause** is diagnosed as **Abount 90% primary hypertension (formely called "essential hypertension")**. - **Secondary hypertension** is the term used when there are **identified cause**. - Primary hypertension is by far most common etiology(病因). ## Contributing cause of **Primary Hypertension** :::danger Primary Hypertension - Genetic problems with the renin-angiotensin-aldosterone system, regulation of endothelial cell function, and arteriolar smooth muscle contraction - Increased total periphral resistance caused by reduced arteriolar radius - Obesity - Insulin resistance (characteristic of type 2 diabetes) - Chronic high salt intake leading to overstimulation of the sympathetic nervous system - Stress - Smoking - Excess alcohol or caffenine consumption - Poor diet - Low birth weight and not being breast-fed as an infant ::: Primary hypertension can be managed with diet, exercise, and life-style changes, and with medication. ## Contributing cause of **Secondary Hypertension** :::danger Secondary Hypertension - **Damage to the kidneys** or their blood supply can lead to **renal hypertension** - Excess renal Na+ reabsorption - Hypersecretion of cortisol, aldosterone, or thyroid hormone - The abnormal nighttime sleeping pattern, sleep apnea ::: Secondary hypertension can be managed with medication. ## Clinical Application - **In coronary artery disease**, changes in one or more of the coronary arteries cause insufficient blood flow(**ischemia**) to the heart - The result may be myocardial damage in the affected region, or even death of that portion of the heart -- a **myocardial infarction, or heart attack** - Sudden cardiac deaths during myocardial infarction are due mainly to **ventricular fibrillation(心室顫動)**, an abnormality in impulse conduction triggered by the damaged myocardial cells - small fration of individuals with ventricular fibrillation **can be saved if emergency resuscitation procedures** are applied immediately after the attack. This is includes **cardiopulmonary resuscitation(CPR) and defibrillation(除顫)** ## Hemostasis(止血) - **Hemostasis** refers to the physiological mechanisms that stop bleeding :::danger Hemostasis involves a 3-step process: - Vascular spasm - Formation of platelet plug - Blood coagulation ::: ## Vascular spasm(血管經攣) When a blood vessel is severed or otherwise injured, its immediate inherent response is to constrict. ## Sequence of events leading to formation of a platelet plug and vasoconstriction floowing damage to a blood vessel wall :::danger ![](https://i.imgur.com/V7y3Bdh.png) **產生出A2** Platelets => Activation and aggregation=> Synthesis of thromboxane A2 ::: ## Formation of a Platelet Plug :::danger - **Platelets adhere to collage**n, largely vai an intermediary called **von willebrand factor(vWF)**, a plasma protein secreted by endothelial cells and platelets. This protein bind to exporsed colleagen molecules, changes its conformation, and becomes able to bind platelets ::: - Binding of platelets to collagen triggers the platelets to release the contents of their secretory vesicles, which contain a variety of chemical agents. **Many of these agents, including adenosine diphosphate (ADP) and serotonin**, then act locally to induce multiple changes in the metabolism, shape, and surface proteins of the platelets, **a process called platelet activation**. Some of these changes cause **new platelets to adhere to the old ones**, a **positive feedback** phenomenon termed **platelet aggregation**, which rapidly creates a platelet plug inside the vessel. ## Blood coagulation : Clot formation - **Blood coagulation, or clotting**, is the transformation of blood into a solid gel called a **clot or thrombus**, which consists mainly of a protein polymer known as **fibrin** - Clotting occurs locally around the original platelet plug and is the dominant hemostatic defense - Its **function is** to **support** and **reinforce** the **platelet plug** and to **solidify blood** that **remains in the wound channel** ## Two clotting pathway-- intrinsic and extrinsic--merge and can lead to the generation of thrombin :::danger ![](https://i.imgur.com/rW8sqlX.png) - (**這題有考**)Hemophilia : fator VIII - Tissue fator: VIIa, VII ::: ## Clotting factors - Clotting factors are produced by the **liver** and are secreted into blood in inactive forms, which are activated during the clotting cascade - Plasma without clotting factors is called **serum(血清)** - **Hemophilia (血友病)** is **genetic disorder** characterized by **deficiencies in clotting factors, usually factor VIII** ## Factors that oppose clot formation - **Tissue factor pathway inhibitor(TFPI)**, s**ecreted mainly by endothelial cells**, **binds to** tissue factor-factor **VIIa** complexes and **inhibits** the ability of these complexe to **generate factor Xa**. - Thrombin binds to an endothelial cell receptor known as **thrombomodulin**, which eliminates all of thrombin's clot-producing effects amd caises the bound thrombin to bind a particular plasma protein, **protein C** and to activate it. Protein C in combination with yet another plasma protein, then **inactivates factors VIIIa and Va** - **Antithrombin III inactivates** **thrombin** and several other clotting factors, and its activity is greatly enhanced when it binds to heparin ![](https://i.imgur.com/7bxOvKb.png) ## Plasminogen Activators(纖維蛋白溶酶原) - **Plasminogen activators** convert **plasminogen** to **plasmin**, and once formed, plasmin digests fibrin, thereby dissolving the clot. - **t-PA(tissue plasminogen activator)** is **secreted by endothelial cells** and, with **plasminogen**, it **binds to fibrin** and becomes **incorporated throughout the clot**. The presence of **fibrin** profoundly **increases the ability of t-PA to catalyze the generation of plasmin from plasminogen** ## Role of Coagulation Factors in Clot formation Disorders - **Hemoplilia** - gentic disorder caused by deficiency of gene for specific coagulation factor - Von Willebrand's disease - Reduced levels of vWF - Decreases platelet plug formation - Vitamin K deficiencies - Decreased synthesis of clotting factors # CH13 ## The respiratory system - The **respiratory system** is intimately **associated with the circulatory system** and is responsible for **taking** up **oxygen** from the environment and **delivering it to the blood**, as well as **eliminating carbon dioxide** from the blood Respiration involves the following 4 steps: - **Pulmonary ventilation (breathing) (肺通氣)** - Exchange of O2 and CO2 between alveolar air and blood in lung capillaries - Transport of O2 and CO2 through pulmonary and systemic circulation - Exchange of O2 and CO2 between blood in tissue capillaries and cells in tissues ## The airways - Structures that comprise the airways incluide: - Nose, nasal cavity(鼻腔), pharynx(咽), larynx(喉), trachea(氣管), bronchi(支氣管), bronchioles, and alveoli(肺泡) Airways beyond the larynx can be divided into two zones: - the **respiratory zone** extends from the respiratory bronchioles down and is the region where **alveoli exchange gases with the blood** - the **conducting zone** from the top of the trachea to the end of the terminal bronchioles, which contains **no alveoli and does not exchange gases with the blood** ## Ciliary Mucous Escalator - This so-called **mucous escalator** is important in **keeping the lungs clear** of particulate matter and many bacterial that enter the body on dust particles - Noxious agents such as **tobacco smoke kills the cilia**. ## Site of Gas Exchange: The Alveoli - The **alveoli** are tiny, hollow sacs whose opend ends are continuous with the lumnia of the airways :::danger - Most of the air-facing surfaces of the wall are lined by a continuous later, one cell thick, of flat epithelial cells termed **type I alveolar cells** **有考(surfactant)** - Interspersed between them are **type II alveolar cells** that produce a detergent-like substance called **surfactant(表面活性劑)** ::: - The **total alveolar-capillary** surface area is **very large** and this is permits the **rapid exchange of large quantities** of oxygen and carbon dioxide **by diffusion** ## Pleural Membranes(胸膜) - Each lung is surrounded by a completely closed sac, the **pleural sac** consisting of thin sheet of cells called **pleura** - The **pleural surface coating the lung** known as the **visceral pleura** is firmly attached to the lung by connective tissue. - Similarly, the outer layer, called **parietal pleura**, is attached to and lins the interior thoracic wall and **diaphragm(橫膈膜)**. - The pleura are separated by an extremely thin layer of **intrapleural fluid** - Changes in the hydrostatic pressure of the intrapleural fluid—the intrapleural pressure 𝑷𝒊𝒑 ## Principles of ventilation - **Ventilation(通氣)** is defined as the exchange of air between the atmosphere and alveoli ## Pressure Measurements - Units of pressure are **millimeters Hg or atmospheres(atm)** - Sea level this is 760 millimeters Hg or 1 atm ## Pneumothorax ![](https://i.imgur.com/SEQrwwS.png) ## Lung Compliance (肺順應性) - **Lung compliance (CL)** is defined as the **magnitude(大小**) of the **change in lung volume produced** by a given **change in the transpulmonary pressure** - Compliance can be considered the **inverse** of **stiffness(剛性)** Two major determinants of lung compliance: - The stretchability of the lung tissues - The surface tension at the air-water interfaces within the alveoli ## Lung compliance and surfactant :::danger - The **type II alveolar cells** secrete the detergent-like substance known as **surfactant(表面活性劑)** - **Surfactant markedly reduces the cohesive forces** between water molecules on the alveolar surface - Therefor, **surfactant lowers the surface tension**, which **increases lung compliance** and makes it **easier to expand the lungs** ::: ## Clinical application - A striking example of what occurs when surfactant is deficient is the diesase known as **respiratory distress syndrome(RDS) if the newborn**. This is a **leading cause of death** in premature infants, in whom the surfactant-synthesizing cells may be too **immature** to function adequately(充分地) - Because of **low lung compliance**, the affected newborn infant can inspire only by the most strenuous efforts, which may ultimately cause **complete exhaustion, inability to breathe, lung collapse, and death** - Current therapy includes assisted breathing with a mechanical ventilator and **the adminstration of natural or synthetic surfactant given through the infant's trachea** ## Airway resistance - Airway resistance to airflow is normally so small that very small pressure differences produce large volumes of airflow - Physical, neural, and chemical factors **affect airway radii** and therefore resistance. ## Asthma(哮喘) :::danger 有考發生孝喘的原因 ::: - **Asthma** is a disease characterized by intermittent episodes in which **airway smooth muscle contracts strongly**, markedly increasing airway resistance - The **basic defect in asthma is chronic inflammation** of the airways, the causes of which vary from person to person and include, among other; **allergy, viral infection, and sensitivity to environmental factors** - The underlying inflammation makes the airway smooth muscle hyperresponsive and causes it to contract strongly in response to such thing as exercise(**especially in cold, dry air**), **tobacco smoke, environmental pollutants, viruses, allergens**, normally released **bronchoconstrictor** chemicals, and a variety of other potential trggers - The first aim of **therapy** for asthma is to **reduce the chronic inflammation** and airway **hyperresponsiveness** with **anti-inflammatory drugs**, particularly **leukotriene(白三烯) inhibitors** and inhaled **glucocorticoids** - The second aim is to **overcome acute excessive airways smooth muscle contraction** with **bronchodilator drugs**, which relax the airways. For exmaple, mimics the normal **action of epinephrine on beta-2** adrenergic receptos - Another class of inhaled drugs block **muscarinic** and **cholinergic** receptors, which have been implicated in bronchoconstriction ## Chronic Obstructive Pulmonary Disease(COPD;慢性阻塞性肺疾病) - The term chronic obstructive pulmonary disease (COPD) refers to **emphysema, chronic bronchitis**, or a combination of the two - These disease cause sever difficilties not only in **ventilation**, but in **oxygenation of the blood** - **Emphysema(肺氣腫)** is caused by destruction and collapse of the smaller airways - **Chornic bronchitis(慢性氣管炎)** is chracterized by **excessive mucus production in the bronchi and chronic inflammatory changes in the small airways** ## Carbon monoxide Poisoning(一氧化碳中毒) - **Carbon monoxide(CO)** is a colorless, odorless gas, that at high concentrations, has an **extremely high affinity--210 times that of O2** - Inhalation(吸入) of CO is a common cause of sickness and death due to poisoning, both intentional and accidental ## Effect of various factors on hemoglobin :::danger **這題有考** The affinity of hemoglobin for oxygen is decreased by - Increased H+ concentration - Increased Pco2 - Increased temperature - Increased DPG concentration >The affinity of hemoglobin for both H+ and CO2 is decreased by increased Po2; that is, deoxyhemoglobin has a greater affinity for H+ and CO2 than does oxyhemoglobin ::: - **Morphine, barbiturates, fentanyl, and heroin, suppress the medullary inspiratory neurons**, and death from overdose of these drugs can be due to the cessation of breathing. ## Major stimuli for the central and Peripheral chemoreceptors :::danger baroreceptor ![](https://i.imgur.com/mmCKtRf.png) peripheral chemoreceptor ![](https://i.imgur.com/c2ZeBah.png) - **Peripheral chemoreceptors: carotid bodies and aortic bodies**-- respond to chnages in the arterial blood. They are stimulated by: - **Significantly decreased Po2(hypoxia)** - **Increased H1 concentration(metabloic acidosis)** - **Increased Pco2 (respiratory acidosis)** **Central chemoreceptors:located in the medulla oblongata**-- respond to changes in the brain extracellular fluid. They are **stimulated by increased Pco2** via associated **changes in H+ concentration** ::: ## Low Arterial Po2 causes Hyperventilation ![](https://i.imgur.com/QkauWqs.png) ## Hypoxia(缺氧) :::danger **Hypoxia** is a deficiency of oxygen **at the tissue level** - **Anemic hypoxia(貧血缺氧)** or **carbon monoxide hypoxia**: the **arterial Po2 is normal but** the total **oxygen content** of blood is **decreased** **because** of **inadequate numbers of erythrocytes**, **deficient or abnormal hemoglobin or** competition for the hemoglobin molecule by **carbon monoxide** - **Ischemic hypoxia (缺血性缺氧):** blood flow to the tissue is too low - **Histotoxic hypoxia(組織中毒性缺氧)**: the body's cells are **unable to use O2 because a toxic agent** has interfered with the cell's metabolic machinery (cyanide causes this) - **Hypoxemic hypoxia(hypoxemia)(低氧性缺氧)**: **reduced arterial Po2** (can be caused **by lack** of **oxygenated air**, **pulmonary problems**, lack of ventilation-perfusion matching) ::: ## Acclimatization to the hypoxia of high altitude The peripheral chemoreceptors stimulate ventilation. - erythropoietin - DPG increases - Increases in skeletal muscle capillary density - Plasma volume can be decreased ## Sleep Apnea(睡眠呼吸暫停) The doctor ordered a sleep study and the diagnosis of **obstructive sleep apnea** was made. The patient was treated with **continuous positive airway pressure (CPAP)** at night. ![](https://i.imgur.com/Kne7SHb.png)