INTRODUTION   

Physiology is the branch of biology that deals with the normal functions of living organisms and their parts; 

  Physiology can be defined more specifically in several ways:  

1. It is the study of life processes that occur inside the body at all levels of organization: cells, tissues, organs, organ systems, and the interactions among these.  

• It is very closely related to chemistry and physics.

2. It is the study of “cause and effect” with an emphasis on the mechanisms of “how does this work.”

• A generalized example would be “what causes the heart to pump and what is its effect on the circulatory system.”

• Or more specifically we could say “what causes the pancreas to secrete insulin and what effect does this have on blood glucose levels.”

3. It is based upon careful observation and experimentation from which conclusions may be drawn. The data collected from these experiments and observations are always open to interpretation and change.

• Everything we are going to study this semester, from cells to reproduction, is based on careful scientific investigation, as produced by what is called the scientific method. It is not infallible, but is in fact, designed to be open to change and modification—self-correcting philosophy.  

• Example: Can test whether athletes have lower resting heart rates than sedentary people. 

4. The ultimate goal of physiological research is to understand the normal functioning of cells, organs, & systems. YOU CANNOT MODIFY (MUCH) WHAT YOU DO NOT UNDERSTAND.  

5. There are also different types of physiology:  

 Pathophysiology is the study of physiological process as affected by injury or disease.

 Exercise physiology is the study of physiological processes as affected by exercise.

 Comparative physiology is the study of the physiology of different invertebrate and vertebrates groups.

Much of the knowledge gained from comparative phys. has benefited mankind, because many other animals, (particularly our closer relatives among Mammalia) have the same or similar physiology. The small differences in physiology between human and other mammals can be of crucial importance in the development of pharmaceutical drugs, but these differences are relatively slight in the overall scheme of things.

Requires an extensive knowledge of anatomy. If you are in this class I'm going to assume you have a working knowledge of anatomy. Review Tissues, Organ Systems, and Cell Organelles. 

The goal of physiology is to explain the physical and chemical factors that are responsible for the origin, development, and progression of life. Each type of life, from the simple virus to the largest tree or the complicated human being, has its own functional characteristics.

Therefore, the vast field of physiology can be divided into viral physiology, bacterial physiology, cellular physiology, plant physiology, human physiology, and many more subdivisions.

Homeostasis.

The study of Physiology generally revolves around the concept of Homeostasis.

 It is a term coined by the father of modern physiology, French physiologist Claude Bernard (1813-1878).

 “homeo” = Greek for like or similar.

 “stasis” = Greek for fixed or stationary.

Homeostasis is the maintenance of the conditions in the cell or within the body that maintain life, despite changes that may be occurring in or outside the body.

1. Your body is going to maintain a constant internal temperature of 98.6˚F (37˚C) no matter what the temperature is on the outside, whether it’s 120◦F or -20◦F.

2. Because the body is an aggregate of about 75 trillion cells, the whole body’s survival is based on the survival of its cells. All bodily processes work together to maintain homeostasis of the internal environment of the cells which keeps you alive.

3. All of the needs of the these cells are supplied by the external environment (e.g. food, water, minerals, oxygen), but because the cells are not in contact with the external environment there must be a means of exchange to get what they need to survive needs and to get rid of their wastes.  

Bodily Fluid Compartments: accomplish this task

1. The body can be thought of as mostly water. Approximately 60% of its weight is water. The fluids contain various mineral ions (e.g. sodium, potassium, chloride) and organic substances (e.g. proteins, glucose) dissolved in the body water. These fluids are grouped into 2 major divisions

• Intracellular fluids (ICF) are the fluids within the cell part of the cytoplasm (water, proteins, enzymes).

• Extracellular fluids (ECF) are all the fluids outside the cell; composed of interstitial or tissue fluid (fluid between cells), plasma (fluid portion of blood, & lymph (fluid in lymphatic vessels)).

• Together these extracellular fluids make up the internal environment of the body, whose constant regulation is the purpose of homeostasis.

Homeostasis: Control of the Internal Environment

1. To reiterate, most of the living cells of the body are not directly exposed to the gaseous external environment (atmosphere), but exist in ECF. 

There is a constant flow or exchange of materials between the ECF & ICF.

2. Because of this constant exchange, conditions in this ECF must be maintained at a relatively constant level (volume & compositions) in order to permit our cells to live & function = homeostasis.

Factors to be maintained in the ECF

 a) Conditions such as O2 and CO2 conc.: cells use O2 for energy & produce CO2 as a waste

 b) pH: correct pH is needed for enzymes to work correctly.

 c) conc. of H2O & electrolytes, such as Na, K, Cl 

 d) temperature: important for enzyme action

 e) concentrations of various nutrients, hormones, & waste products

 f) volume & pressure: important for transfer of materials between plasma and interstitial fluid

3. All are closely regulated by the cooperative workings of body’s tissues, organs, & systems.

• Digestive system transfers nutrients to plasma to cells.

• Respiratory system transfers O2 from external environment to cells, & carries CO2 away.

• Circulatory & lymphatic systems transport nutrients & wastes throughout body.

4. If homeostasis of the internal environment is disrupted, the result is often disease or sickness, which sometimes has a snowball effect. In many diseases, the composition and/or volume of the internal environment become abnormal.

• Consider a person who has kidney failure and cannot get rid of metabolic waste products that are toxic to cells at an adequate rate.

• In such a person, toxic waste materials will accumulate in the ECF and the body will be poisoned by its own internal environment.  The normal functioning of body cells will be disturbed under such conditions.  

• What if someone has respiratory failure? Heart failure? Iron deficiency? Sterility? Some you can live without

5. So the study of physiology revolves around the concept of homeostasis and the regulatory processes by which the body maintains this constancy of the internal environment. 

• Some are simple, some are extremely difficult, but every process in the body has a common goal: to maintain homeostasis of the internal environment of the body.

Homeostasis has been achieved when:  

1. the internal environment has the best (optimum) concentrations of gases, nutrients, ions, & water.

2. the internal environment has the optimal temperature, it varies a little but normal body T is 37°C = 98.6°F.

3. The internal environment has optimal pressure: gas, water, & osmotic pressure.

4. Goldilocks analogy: "everything has to be just right."

Requirements for Maintaining Homeostasis 

1. Communication within the body: accomplished by endocrine & nervous systems. How does each communicate? The factor being regulated is the variable (temp, blood sugar levels, etc.). All homeostatic control mechs. have at least 3 interdependent components (receptor, integrating center, effector).

2. Input from sensory receptors: sensory receptors respond to stimuli (detect changes) to the body, an awareness of what is happening internally & externally.  

3. Control / Integrating center: brain, spinal cord, or endocrine glands. They receive sensory information and bring about a response (efferent signal) via nerve impulses or hormones, intended to change conditions back to normal. The control center determines a set point (the level or range) at which a variable is to be maintained; it analyzes afferent signals & responds with an efferent signal.  

4. Effectors bring about the change specified by the integrating center (e.g., skeletal muscle, glands, & organs). Effectors provide the means for acting on the control center’s response to a stimulus, either depressing it (negative feedback) or enhancing it (positive feedback).  

Military Analogy: field troops detect enemies (sensor) ( send message to HQ (afferent signal to control center) (HQ issues a command & sends message to jets (efferent signal) (jets (effectors) bomb the enemy (boom boom)

To maintain homeostasis, we must have communication networks & mechanisms for regulating this network.

Homeostatic Control Systems: a collection of interconnected cells that function to maintain a physical or chemical property of the internal environment relatively constant.

• Each individual cell exhibits some degree of self-regulation, but the existence of a multitude of cells organized into tissues, which are further combined to form organs, imposes the requirement for overall regulatory mechanisms to coordinate the activities of all cells.

• Example: If you start sprinting, you require more O2, so to maintain O2 in the ECF, we must have a way of detecting O2 concentration and alter respiratory activity so that O2 levels are optimum. Vessels dilate/constrict on a local level before the nervous system is aware.

• As you keep sprinting, other control mechanisms come into play.

Control Systems of the Body: the are 2 general classes of control systems in the body.

1. Local Control: built in or inherent to the organ or tissue itself.

• When you exercise skeletal muscle (as in running), you immediately decrease or use up the available oxygen & nutrients available to those cells. There is also an increase of CO2 & lactic acid (waste products) in the cells.

• This directly triggers smooth muscle relaxation in arterioles in muscle, which increases blood flow (vessel dilation) to the area for more nutrients, O2, and to transport wastes away.

• So, we have specific control of a local area (tissue, organ, etc.) w/o the nervous system being "aware."

2. Reflex Controls: regulatory mechanism outside the organ system that involves the nervous & endocrine systems.

• most widely used means of control.

• initiated by an internal change that is detected by an "external control system" (nervous/endocrine systems). Detect intrinsic response.

• Motor nerve impulses or hormones are released from outside of the tissue/organ to produce a more widespread effect in the body

• Example: So if we keep running for a long period of time, the extrinsic controls will kick in to also help regulate the changes going inside the body: Temp, glucose levels, etc.

3. So if the internal environment is disrupted like in running, the external & internal processes mediate reactions that try to return the body to a desired level = set point. Body wants to keep itself at this relatively constant level = homeostasis.

• A set point is really an average of values within the normal range. The values are constantly changing between the high & low points.

• blood pH varies between 7.35-7.45.

• body T can range from 96.0◦F in the morning to 99.0◦F at night. Organs even have different temperatures. No "normal" T—what we call normal is an average of many people. Remember that 98.6◦F is an oral temperature reading—your normal core T is greater.   

• Analogy of T set on a house thermostat compared to body T maintenance

There are 2 Types of Extrinsic Control Mechanisms:

Negative & Positive Feedback.

Negative Feedback: regulatory mechanism in which a change in a controlled variable triggers a response that opposes the change, thus maintaining a steady set point for the regulated factor. This is the most common extrinsic control system to maintain homeostasis (i.e. it is homeostatic). 

Negative Feedback Involves: Remember our requirements!

1. In order for the internal constancy to be maintained, the body must have sensors that are able to detect deviations from a set point.

• The set point is analogous to the temperature set of a house thermostat.

• In a similar manner, there is a set point for body temp, blood glucose conc., tension on the tendon, etc.

2. Integrator receives info. from the sensors and increases or decreases the activity of the effectors. 

3. Effectors carry out the instructions from the Integrating Center to maintain internal constancy.

Because the activity of the effectors is influenced by the effects they produce, and because this regulation is in a "negative" or "reverse/opposite" direction, this type of control system is known as a negative feedback loop.

It is important to realize that these negative feedback loops are continuous processes — NOT JUST OFF/ON. Thus, a particular nerve fiber that is part of an effector mechanism may always display some activity, and a particular hormone in the blood, may always be present.

Antagonistic Effectors: Most factors (O2, glucose, ions, etc.) in the ECF/Internal environment are controlled by several effectors, that often have opposite effects. These are called antagonistic effectors and they have "push-pull" effects. Tonic control refers to ongoing control that’s adjusted up & down.

• tonic control: increasing the activity of one effector in turn decreases the activity of an antagonistic effector.

• Example: Blood glucose levels are regulated by negative feedback loops involving hormones that have opposite effects. While insulin lowers blood glucose levels, glucagon raises blood glucose levels.

Positive Feedback: is the opposite of negative feedback!! The action of the effector amplifies the changes that first stimulated the effectors. There are no antagonistic factors.

• If the change in the homeostatic condition were to increase, positive feedback increases it even further.

• Back to the thermostat example, usu. it maintains a constant T by increasing heat production when it is cold and decreasing heat production when it is warm = negative feedback. A thermostat that works by positive feedback, would increase heat production in response to a rise in temperature.

A reflex action is not homeostatic—the response amplifies/reinforces the stimulus, rather than having an opposite effect. It can only be stopped by removing the stimulus. Shine light in someone’s eyes, pupil contracts & stays contracted until the stimulus is removed. Hit someone on the patellar ligament & keeping hitting them, body will keep jerking knee.  

• Blood clot: initial damage caused by a cut, sets off a series of reactions to form a clot. The activation of one clotting factor results in the activation of other clotting factors in a positive feedback avalanche-like manner.

• Giving Birth. Birth initiation starts with uterine contraction, which causes oxytocin release. This stimulates contraction of more uterine smooth muscle which stimulates more oxytocin release. Contractions keep getting stronger and stronger. Production stops only after baby and placenta have been completely delivered.

• A single change is amplified to produce a blood clot or to give birth. Aid in the completion of negative feedback loops.

• Essentially uncommon, because it tends to move the conditions further away from homeostatic levels. Prolonged positive feedback is generally detrimental and usually pathogenic.

FEED FORWARD CONTROL

Negative feedback loops can stabilize a function and maintain it within a normal range, but are unable to prevent the change that triggered the reflex in the first place. A few reflexes have evolved that allow the body to predict that a change is about to occur and start the response loop in anticipation of the change. These responses are called feedforward controls (example = salivation reflex: sight, smell, or thought of food is enough to start the response loop, which also trigger the release of HCl in the stomach).

Others examples:

• erection in human males (visual or tactile stimuli)
• response to exercise (visualization of an event in your mind)
• relaxation techniques.

CIRCADIAN RHYTHMS

Unlike some reflex loops which require a stimulus, some occur spontaneously, e.g., hormones are secreted at different levels at different times of the day. Most occur in a predictable manner and are often timed to coincide with a predictable environmental change such as light-dark cycles or the seasons. Circadian rhythms are regular rhythms of growth or activity that occur on a 24 hour cycle.

controlled by the hypothalamus, which receives information from an ascending pathway from the retina via the suprachiasmatic nucleus. 

studying at night ( get cold not because of drop in environmental temp, but because your thermoregulatory reflex has turned down your internal thermostat

others that vary are cortisol (steroid hormone that regulates metabolism; secreted from the adrenal gland); levels are at their lowest at 4 AM and peak around 9 AM in the morning.  

growth hormone

sex hormones (testosterone levels peak at midnight and in the morning hours)

morning people (temps rise before they wake up and drop off early in the evening) vs. night owls (tough time waking up but maintain body temps longer)

Effects vary with age and state of well-being.

People who work night shifts never really quite adjust, because even though their body wants to rest, the control centers of the brain tell them it’s time to get up.

Biological reflexes are mediated by the nervous system, the endocrine system, or both. Reflexes can be quite complex, passing through many integrating centers before reaching the effector. There is so much overlap between reflexes controlled by the nervous & endocrine systems that they should be considered as a continuum rather than two discrete systems. 

CONTROL SYSTEMS vary in speed, specificity, duration, signal type, and intensity because tissues require different means of responses for different functions.  

Specificity

nerves are specific, can trace a pathway from origin to its target cells

endocrine control is more general: hormone is released into the blood; however, receptors on the cell membrane ensure the response is cell/tissue specific.

Nature of the Signal Nervous system uses both a electrical (depolarization travel long distances) and chemical signals (NT’s travel short distances)

Endocrine system uses chemical signals only

Speed Nerves are much faster than endocrine reflexes because hormones must be distributed through the circulatory system

Duration of Action

Nerve control has a much shorter duration than endocrine

short-term functions mostly performed by the nervous system

long-term by the endocrine system

Intensity

frequency of nervous impulses relays stimulus intensity (i.e. how fast)

hormone concentration relays stimulus intensity (i.e. how much)

Dynamic Constancy and the Steady State

• Because negative feedback loops respond after deviations from the set point have stimulated sensors, the internal environment is never absolutely constant.

• Homeostasis is best described as a state of dynamic constancy, in which conditions hover above and below the set point.

• In other words, feedback systems do not maintain a complete constancy. The internal environment varies around the set point. (i.e. it oscillates around set point)

• Feedback systems just try to minimize the changes taking place.

• Example: If you are exposed to extremely cold temperatures, as long as the exposure to cold continues, some decrease in body temperature must persist to serve as a signal to maintain the responses of the effectors & antagonists. 

Homeostatic imbalance

1. Homeostasis is so important that most disease is regarded as a result of its disturbance, a condition called homeostatic imbalance.

2. As we age, our organs & control systems become less efficient, placing us a greater risk for illness.

3. Another source of homeostatic imbalance occurs in certain pathological situations when the usual negative feedback mechanisms are overwhelmed and destructive positive feedback mechanisms take over, such as in heart failure.  

Important Generalizations about Feedback Mechanisms:  

1. Stability of an internal environmental variable is achieved by balancing inputs and outputs. The balance between variables - inputs & outputs is the concern.

2. In negative feedback systems, a change in the variable being regulated brings about responses that tend to push the variable in the direction opposite to the original change back toward the original value.

3. Homeostatic control systems cannot maintain complete constancy of any given feature of the internal environment - regulated values will have a narrow range of normal values.

4. It is not possible for everything to be maintained constant by homeostatic control mechanisms—some controls are more important than others, and therefore, are regulated more. 

The Lymphatic System and Immunity

The immune system is the complex collection of cells and organs that destroys or neutralizes pathogens that would otherwise cause disease or death.The lymphatic system is the system of vessels, cells, and organs that carries excess fluids to the bloodstream and filters pathogens from the blood.

Functional Anatomy of the Lymphatic and Immune Systems

Functions of the Lymphatic System:

The lymphatic system drains excess interstitial fluid from the interstitial space and transports it to the bloodstream. Once this tissue fluid enters into the lymphatic vessels, it is no longer called interstitial fluid; it is now referred to as lymph. Any blockage in the normal drainage of lymph produces lymphedema.

The lymphatic system houses the phagocytic cells and lymphocytes that clean the tissue fluid before it is dumped into circulation.

The lymphatic system absorbs digested fats from the intestine by specialized lymph vessels called lacteals. The fatty lymph is known as chyle.

Structure of the lymphatic system

The lymphatic system includes thevessels, cells, tissues,and organs responsible for defending the body against both environmental hazards (such as various pathogens) and internal threats (such as cancer cells).

Lymph Vessels: carry lymph from the peripheral tissues to the venous system. The lymphatic network begins with lymphatic capillaries, which merge to form progressively larger vessels as they make their way towards circulation.

Lymph capillaries: present in almost every tissue and organ in the body; are believed to be as abundant as blood capillaries.  

Lymph capillaries are absent, however, in areas of the body that lack a blood supply, such as the cornea of the eye, and are also absent from the central nervous system and bone marrow.

Lymphatic capillaries differ from blood capillaries in that they

1) are blind-end tubes,

2) have larger diameters with lower resistance and pressure,

3) have thinner walls that are more permeable, and

4) typically have a flattened or irregular shaped lumen.

Although lymphatic capillaries are lined by simple squamous epithelium, the basal lamina is incomplete or absent. Furthermore, the endothelial cells overlap forming a type of one-way valve called a mini-valve. The mini-valves permit the entry of fluids and solutes (such as proteins) as well as viruses, bacteria, and cell debris, but prevent their return to the intercellular spaces.

Lymph collecting vessels: from the lymph capillaries, lymph flows into larger lymph collecting vessels with valves that lead toward the body’s trunk.

Lymph trunks: the superficial and deep lymph collecting vessels converge to form larger vessels known as lymphatic trunks and are named by the areas of body they drain:

The jugular trunks are located in the neck and drain the head.

The subclavian trunks are located in the shoulders and drain the arms.

The bronchomediastinal trunks are located in the chest and drain the thoracic cavity and lungs.

The lumbar trunks are located in the lower back and drain the pelvis and lower limbs.

The intestinal trunk is located in the abdomen and drains the walls of the digestive organs.

Blockage of the lumbar trunks or subclavian trunks by a filarial worm,such asWuchereriabancrofti, causes severe lymphedema known asElephantiasis.

Lymph ducts: the lymph trunks merge to form the two largest lymphatic vessels called the right lymphatic duct and thoracic duct.

The right lymphatic duct forms from the merger of the right jugular trunk, the right subclavian trunk and the right bronchomediastinal trunk. The right lymphatic duct drains the right side of the head, right arm, right shoulder, and right side of the thoracic cavity. The right lymphatic duct empties into the right subclavian vein.

The thoracic duct ascends along the left side of the vertebral column, collecting lymph from the left bronchomediastinal trunk, the left subclavian trunk, the left jugular trunk. At the base of the thoracic duct is an enlarged sac-like chamber called the cisterna chyli which receives lymph from the lumbar trunk and intestinal trunk. The thoracic duct drains the left side of the head, the left arm, the left shoulder, and the left side of the thoracic cavity, all of the abdomen, pelvic region and both legs. It empties into the left subclavian vein.

The Organization of Immune Function

Barrier defensessuch as the skin and mucous membranes, which act instantaneously to prevent pathogenic invasion into the body tissues

Innate immune response – rapid, non-specific response consists of a variety of specialized cells and soluble factors

Adaptive immune response – slower, specific and effective, involves many cell types and soluble factors, but is primarily controlled by white blood cells (leukocytes) known as lymphocytes, which help control immune responses

In adults, erythropoiesis is normally confined to red bone marrow, but lymphocyte production, called lymphopoiesis, involves the red bone marrow, thymus, and peripheral lymphoid tissues. WBCs can be divided into three classes based on function:

Phagocyticcells - ingest pathogens to destroy them

Lymphocytes- specifically coordinate the activities of adaptive immunity

Granular WBCs- help mediate immune responses against parasites and intracellular pathogens such as viruses

Lymphocytes: B Cells, T cells, Plasma cells and Natural Killer cells

Althoughlymphocytes account for 20-30 percent of the circulating leukocyte populations, circulating lymphocytes are only a small fraction of the total lymphocyte population. The majority of these reside within the lymph organs of the body such as the lymph nodes, spleen, tonsils, thymus, etc.

Three classes of lymphocytes circulate in blood and aresensitive to specific antigens:

B cells – account for 10-15 of circulating lymphocytes. B cells are said to be responsible for antibody-mediated immunity (akahumoral immunity) because antibodies circulate widely within body fluids and attack targets with foreign antigens.When stimulated by an antigen, B cells differentiate into plasma cells.

Plasma cells, which produce and secrete antibodies. Plasma cells differ in morphology from standard B and T cells in that they contain a large amount of cytoplasm packed with the protein-synthesizing machinery known as rough endoplasmic reticulum.

T cells – approximately 80 percent of the circulating lymphocytes are classified as T cells. T cells are diverse and provide cell-mediated immunity (discussed later).

Natural Killer (NK) cells–only about 5-10 percent of circulating lymphocytes are Natural Killer cells. This particular group of lymphocytes is part of the body’s non-specific defenses and they using cytotoxic granules to attack foreign cells, body cells infected with viruses, and cancer cells that appear in normal tissues. Their continuous monitoring of peripheral tissues has been called immunological surveillance.

Primary Lymphoid Organs and Lymphocyte Development

Red bone marrow. Blood cells are made in the yolk sac in an embryo. This function is taken over by the spleen, lymph nodes, and liver as the embryo develops. Later, the bone marrow takes over most hematopoietic functions, although the final stages of the differentiation of some cells may take place in other organs.

Thymocytes - immature T cells leave the bone marrow and mature largely in the thymus gland.

Thymus – produces several hormones, collectively called the thymosins, that are important to the development of functional T cells, and thus to the maintenance of normal body defenses.

The thymus is large when a person is born and continues to grow through childhood as the individual is exposed to infection. By puberty, the thymus weighs 40 g. However, after puberty, it gradually diminishes in size and becomes increasingly fibrous in a process known as involution. By the time an individual reaches age 50, the thymus may weigh less than 12 g and is correlated with an increase in susceptibility to infection and disease.

The thymus is surrounded by a capsule that divides it into left and right lobes. Fibrous partitions called septa originate at the capsule and divide the lobes into lobules averaging 2 mm in diameter.

Each lobule consists of a dark outer cortex and a lighter central medulla. The medulla is dominated by thymic corpuscles not present in the cortex.

Secondary Lymphoid Organs and their Roles in Active Immune Responses. 

Naïve lymphocyte- one that has left the primary organ and entered a secondary lymphoid organ. Naïve lymphocytes are fully functional immunologically, but have yet to encounter an antigen to respond to.

Lymph nodes – are small lymphoid organs ranging in diameter from 1 mm to 25 mm. The shape of a typical lymph node resembles that of a kidney bean. The largest collections of lymph nodes are located in the cervical region, axillary region, and inguinal region. As lymph flows through a lymph node, at least 99% of the antigens in the lymph are removed and the immune response is stimulated as needed. Swollen lymph nodes are called buboes. The path of lymph flow through a lymph node is as follows:

Afferent lymphatic vessels – transport “dirty” lymph into the lymph node from the peripheral tissues. The afferent lymphatic vessels penetrate the capsule of the lymph node on the side opposite the hilum (a shallow depression where the blood vessels and nerves enter and leave the organ).

The afferent vessels deliver the lymph to the subcapsular space, a meshwork of reticular fibers, macrophages, and dendritic cells. Dendritic cells are involved in the initiation of the immune response.

Lymph next flows in the outer cortex which contains B cells within germinal centers that resemble those of lymphoid nodules.

Lymph then flows through the lymph sinuses to the deep cortex which is dominated by T cells.

Lymph continues into the medullary sinuses at the core of the lymph node. This region contains B cells and plasma cells.

Efferent lymphatic vessels– drain the “cleaned” lymph out of the lymph node and exit at the hilum.

Spleen–is the largest lymphoid organ and performs the same functions for blood that the lymph nodes perform for lymph. The spleen removes abnormal red blood cells, stores iron from recycled RBCs, and initiates immune response by B cells and T cells to antigens in the bloodstream.

The spleen lies along the curving lateral border of the stomach. It is attached to the lateral border of the stomach by the gastrosplenic ligament, a broad band of mesentery. The outer surface, called the diaphragmatic surface, is smooth and convex, conforming to the shape of the diaphragm and body wall.

The spleen is surrounded by a capsule containing collagen and elastin fibers. The spleen tears so easily that a seemingly minor impact to the left side of the abdomen can rupture the capsule. Because it is so fragile, it is difficult to repair and is instead typically removed in a process called a splenectomy. 

Splenic blood vessels and lymphatic vessels communicate with the spleen on the medial surface (also called visceral surface) at the hilum. The medial surface also has two shallow depressions that conform to the shape of the stomach (gastric area) and that of the kidney (renal area).

Fibrous partitions, called trabeculae, radiate outward toward the capsule through the interior from the hilum. Blood vessels travel within the trabeculae.

The cellular components within the spleen constitute the pulp. The red pulp contains large quantities of red blood cells, whereas the white pulp resembles lymphoid nodules and contains lymphocytes.

The unusual circulatory arrangement within the spleen gives the phagocytes of the spleen an opportunity to identify and engulf any damaged or infected cells in circulating blood. 

Lymph nodules-areas of densely packed lymph tissue or lymphocytes.Houses a specialized form of connective tissue called reticular connective tissue which resembles areolar tissue but contains larger numbers of collagen, elastin, and reticular fibers. Their boundaries are not distinct because although they may cluster together and form large masses, there is no fibrous capsule surrounding them.

Tonsilsare large lymphoid nodules in the walls of the pharynx. Left and right palatine tonsils are located at the posterior, inferior margin of the oral cavity. A single pharyngeal tonsil (often called the adenoid) lies in the posterior superior wall of the nasopharynx, and a pair of lingual tonsils lies deep to the mucous epithelium covering the base of the tongue. A final pair of tonsils, called the tubal tonsils, is found in the base of each of the pharyngotympanic tubes. Most of the time, our tonsils go unnoticed unless they are infected and swollen, a condition known as tonsillitis.

Mucosa-associated lymphoid tissue (MALT) protects the rest of the epithelia of the digestive, respiratory, urinary, and reproductive tracts from pathogens and toxins.  

A variety of clinical disorders can result from infection and/or inflammation of the MALT components such as appendicitis (inflammation of lymphoid tissue from the appendix).

Aggregated lymphoid nodules, or Peyer’s patches, are a type of MALT, found clustered deep in the epithelial linings of the distal small intestine. Each nodule has a central zone, called the germinal center, which contains rapidly-dividing lymphocytes.

Bronchus-associated lymphoid tissue (BALT) consists of lymphoid follicular structures with an overlying epithelial layer found along the bifurcations of the bronchi, and between bronchi and arteries.

Cancer originating in any lymphoid cells or tissues is called lymphoma. Hodgkin’s lymphoma is characterized by the presence of Reed-Sternberg cells and has been associated with the Epstein-Barr virus in 70% of cases. All other types of lymphoma are called Non-Hodgkin’s lymphoma of which there are at least 61 types.

21.2 Barrier Defenses and the InnateImmune Response

Characteristics of the innate body defenses:

Innate defenses are present and functioning at birth.

Innate defenses are non-specific, that is, they do not distinguish one threat from another and respond the same way regardless of the invading agent.

Innate defenses tend to be more localized and generally attack the infection where the invading agent is attempting to gain entry into the body.

Innate defenses have no memory. Regardless of the number of times the body encounters the invading agent, innate defenses do not improve their response to the infection.

Innate immunity includes physical barriers, cellular defenses via phagocytes and NK cells, and chemical defenses via complement, inflammatory chemicals, interferon, and pyrogens.

PHYSICAL BARRIERS – keep hazardous organisms and materials outside the body.

Skin – the integumentary system provides the major physical barrier to the external environment.

The epidermis of the skin is composed of stratified squamousepithelium with keratinized cells and a network of desmosomes that lock adjacent cells together.

Hairs found on most areas of the body’s surface provide some protection against mechanical abrasion (especially on the scalp), and they often prevent hazardous materials or insects from contacting the skin.

The epidermal surfaces receive the secretions of sweat glands. These secretions, which flush the surfaces to wash away microorganisms and chemical agents, may also contain bactericidal chemicals called defensins, destructive enzymes called lysozymes, and antibodies.

The epidermal surfaces receive secretions from sebaceous glands. Sebum not only lubricates the skin but also reduces the amount of free water on the surface of the skin, thereby creating an arid environment that most microorganisms find inhospitable.

Mucous membranes – the epithelial linings of the digestive, respiratory, urinary, and reproductive tracts provide a barrier that most organisms cannot cross.

Mucus bathes the surfaces of the mucous membranes. The mucus captures most microorganisms and debris so that it cannot gain entry past the delicate internal passageways.

Mucous membranes also secrete chemicals that reduce the growth of microorganisms: powerful acids, lysozymes, and defensins.

The cells of mucous membranes are held together by numerous tight junctions and supported by a fibrous basal lamina.

Mucous membranes often possess cilia that create an outward wave of movement that transports microorganisms up and out of the body.

Mucous membranes possess MALT (mucosa-associated lymphatic tissue).

CELLULAR DEFENSES – if the hazardous organism gains entry into the body, cells attack the infection at the site of entry.

Phagocytic cells – cells that engulf pathogens and cell debris should they make it past the physical barriers created by the skin and mucous membranes.

Characteristics common to all phagocytes:

Phagocytes can leave capillaries by squeezing between adjacent endothelial cells in a process known as diapedesis, or emigration.

Phagocytes are attracted to chemicals produced by infection in a phenomenon called positive chemotaxis.

Phagocytosis always begins with the attachment of the phagocyte to its target cell. In this process, called adherence, receptors on the plasma membrane of the phagocyte bind to the surface of the target.

After attachment, the phagocyte may either destroy the target itself or promote its destruction by activating T cells and B cells.

Different types of phagocytic cells:

Neutrophils – the most abundant leukocytes; they are highly mobile and quick to phagocytize cellular debris or invading bacteria. They circulate in the bloodstream and roam through the peripheral tissues, especially at the sites of injury or infection.

Eosinophils – less abundant than neutrophils and have limited abilities to phagocytize compared to neutrophils; they engulf foreign pathogens only it they’ve been coated with antibodies.

Monocytes – less numerous than neutrophils but more numerous than eosinophils; give rise to types of macrophages: free and fixed.  

Free macrophages travel throughout the body, arriving at the site of injury by migrating through adjacent tissues or by recruitment from the circulating blood. An example of a free macrophage would be dendritic cells.

Fixed macrophages are permanent residents of specific tissues and organs and are scattered among connective tissues. They normally do not move within these tissues. An example of a fixed macrophage would be the kupffer cells of the liver.

NK cells – detect and destroy abnormal body cells or virus infected cells.

Generally the immune system ignores the body’s own cells unless they become abnormal in some way such as cancer cells. The constant monitoring of normal tissues by Natural Killer (NK) cells is called immunological surveillance. NK cells are also able to recognize bacteria, foreign cells, and cells infected by viruses.

In each case, the steps leading to destruction of the target cell are similar:

Step one: If a cells has unusual components in its plasma membrane, NK cells recognize the cell as abnormal and adhere to the cell.

Step two: Large numbers of secretory vesicles are produced by the golgi apparatus. These vesicles, which contain the proteins called perforins, travel through the cytoplasm toward the cell surface.

Step three: The perforins are released at the cell surface by exocytosis and diffuse across the narrow gap separating the NK cell from its target.

Step four: The perforins create holes or pores in the plasma membrane of the target cell so that it can no longer maintains its internal environment and it quickly disintegrates.

CHEMICAL DEFENSES – substances that destroy the organism, label it as an invading cell, prevent it from reproducing in the body, or stimulate other immune system cells to respond.

Interferons – an example of a cytokine, interferons are secreted by lymphocytes, macrophages, and tissues infected with viruses.

When a virus is 

CHEMICAL DEFENSES – substances that destroy the organism, label it as an invading cell, prevent it from reproducing in the body, or stimulate other immune system cells to respond.

Interferons – an example of a cytokine, interferons are secreted by lymphocytes, macrophages, and tissues infected with viruses.

When a virus is in the body, interferons are secreted to protect healthy cells. On reaching the membrane of a normal cell, the interferon binds to surface receptors on the cell and via a second messenger, triggers the production of antiviral proteins within the cell’s cytoplasm.  

Antiviral proteins do not interfere with the entry of viruses but instead interfere with viral replication inside the cell thereby preventing the spread of the virus.

At least three types of interferons exist:

1. Alpha interferons – produced by viral infected cells to attract NK cells and enhance resistance to viral infection.
2. Beta interferons – secreted by fibroblast to slow inflammation in a damaged area.
3. Gamma interferons – secreted by T cells and NK cells to stimulate macrophage activity.

Complement – a system of 11 circulating proteins that assist, or complements, antibodies in the destruction of pathogens.

There are two pathways for complement action and both are described as an enzyme cascade leading to a series of common steps:

Classical pathway: the most rapid and effective activation of the complement system also sometimes called the antigen-antibody complex.

The classical pathway begins when one of the complement proteins attaches to antibody molecules already bound to their specific antigen.

The attached complement protein then acts as an enzyme, catalyzing a series of reactions involving other complement proteins.

Eventually an activated complement protein binds to the bacterial cell wall which then enhances lysis of the foreign cell, opsonization and phagocytosis of the foreign cell, or histamine release triggering the inflammatory response.

Alternative pathway: most important in the defense against bacteria, some parasites, and virus infected cells.

The alternative pathway begins when several complement proteins, notably factor B, factor D, and properdin, interact in the plasma. The interaction of these complement proteins can be triggered by exposure to foreign materials, such as the capsule of a bacterium.  

The end result is the attachment of an activated complement protein to the bacterial cell wall which then enhances lysis of the foreign cell, opsonization and phagocytosis of the foreign cell, or histamine release triggering the inflammatory response.

Inflammatory chemicals – localized, tissue-level response that tends to limit the spread of an injury or infection.

The inflammatory response follows a complex process:

Step one: tissue damage (including impact, abrasion, distortion, chemical irritation, infection by pathogens, and extreme temperatures) can induce inflammation.

Step two: injured or infected tissues release prostaglandins, cytokines, potassium ions, pyrogens, and a host of other “alarm chemicals”.

Step three: mast cells and basophils are activated; these then release histamine and heparin 

The flood of chemicals into the body fluids induce numerous changes:

• Vasodilation increases blood flow to the site of damage
• Increased permeability of the local blood vessels causes exudate to seep out of the bloodstream.
• Fibrin threads form a network that occludes lymph vessels which limit the removal of lymph which in turn, reduces the spread of infection. In combination with increased permeability of blood vessels, this causes swelling, oredema.

Leukocytosis – stimulation of increased WBC production

Positive chemotaxis – activated phagocytes, especially neutrophils, are attracted to the site of injury where they begin phagocytizing foreign and injured cells.

The four cardinal signs of inflammation: redness, heat, swelling, and pain.

Pyrogens – a fever-inducing chemical that elevates the body temperature which in turn, accelerates tissue metabolism, tissue repair, and the activity of immune defenses.

Fever is defined as the maintenance of body temperature above 37.2o C (or 99oF). For each 1oC rise in body temperature, metabolic rate jumps by 10%.

Within limits, an increase in body temperature may be beneficial because it can inhibit the growth and reproduction of bacteria and viruses and can stimulate increased metabolism and tissue repair.

However, beyond a certain threshold, high body temperature can begin to denature proteins which could actually shut down normal immune response.

 The Adaptive Immune Response: T lymphocytes and Their Functional Types

Characteristics of the adaptive immune defenses:

• Adaptive defenses are not present and functioning at birth and are instead developed as a result of exposure to infections and their antigens.
• Adaptive defenses are specific, that is, they recognize and attack one infection with one specific antigen while ignoring all other infections with different antigens.
• Adaptive defenses tend to be more systemic and can attack the infection anywhere and everywhere in the body not just where it got in.
• Adaptive defenses have memory. With each exposure to the infection, the adaptive defenses modify and improve their response to the infection so that the response is faster, stronger, and longer-lasting.
• Adaptive defenses are versatile. Because exposure to the infection causes the adaptive cells to multiply, clones that are all specific to the infection are produced. Each clone can then take on a different role in the immune response to the infection.
• Adaptive defenses exhibit tolerance. The immune system ignores normal body tissues (recognized as “self”) while it targets abnormal body tissues (recognized as “non-self”).

There are two main types of adaptivedefenses: cell mediated immunity and antibody-mediated immunity:

CELL MEDIATED IMMUNITY

Properties of Cell Mediated Immunity:

Provided by the action of T-lymphocytes which are produced in the red bone marrow but mature in the thymus gland.

T-lymphocytes cannot recognize antigen directly, instead the antigen must be processed and presented to the T-lymphocyte by either specialized Antigen Presenting Cells (APCs) or infected body cells.

Antigen presentation occurs when glycoproteins on the surface of APCs or body cells display an antigen or a piece of the antigen. These membrane glycoproteins are called major histocompatibility complexes or MHC proteins.

There are two classes of MHC proteins:

Class I MHC proteins – found on every body cell to allow body cells infected with virus to alert the immune system that they’ve been attacked by infection and reveal the identity of their attacker.

Class II MHC proteins – found only on the membranes of APCs (which may be macrophages, other phagocytic cells such as neutrophils or eosinophils, and dendritic cells). Class II proteins allow APCs to alert the body that infection has been discovered and stimulate other immune system cells to rush to the site of infection to help with the attack.

Stimulation and Clonal expansion of T cells

When macrophages patrolling the body tissues encounter foreign organisms, they engulf them by phagocytosis. Once the organism is inside the macrophage, the macrophage processes the antigen and exposes it on the surface of its own cell in combination with the Class II MCH protein. The antigen -class IIMHC complex can only be recognized by the cell that possesses a special CD4marker. The only cells that possess the CD4 marker are the CD4 T cells that differentiate to formTH cells and memory TH cells. The TH cells begin secreting cytokines which now alert other B and T lymphocytes that an infection has been located and guides these cells to the site of infection by positive chemotaxis.

On the other hand, if a body cell becomes infected by a virus, it can alert the body that it has been attacked. Once the virus is inside the body cell, the body cell takes pieces of the abnormal peptides of the virus and incorporates them with MCH proteins on their surface. Typical body cells however do not possess the Class II MCH proteins that macrophages possess. Instead, they possess the Class I MHC proteins that bind to the foreign antigen and stimulate only cells that possess the CD8makers. CD8 T cells differentiate to form TC cells, TS cells and Memory TC cells. When the TC cell recognizes the antigen-MHC Class I complex, the cytotoxic T cells destroy the “sick” body cell by perforins, by activation of genes within the body cell which trigger apoptosis of the body cell, and disruption of the cell’s metabolism through the release of lymphotoxins.

Four types of T-cell clones are produced during infection:

1. Helper T cells – TH cells or CD4 T-cells, produce cytokines that stimulate the proliferation of all other immune cell types (including more phagocytic cells, T-cells, and B-cells) to join the attack against the infection.
2. Cytotoxic T cells – TC cells, also called killer T cells; stimulated by infected body cells and helper T cells to attack virus-infected body cells and cancer cells.
3. Suppressor T cells – TS cells, shut down the activity of T cells and B cells once the infection has been conquered by the secretion of suppression factors.
4. Memory T cells – cells that remain in circulation long after the infection is over to respond to future infections by the same pathogen.

Adaptive Immune Response: B-lymphocytes and Antibodies 

Properties of Antibody Mediated Immunity:

Provided by the action of B-lymphocytes which are produced in the red bone marrow and remain there to mature.

Also called Humoral Immunity because B-lymphocytes attack the infection or their antigens while in the body fluids (blood, lymph, interstitial fluid, etc.)

Although B-lymphocytes reside in the spleen and lymph nodes many are also circulating in the body fluids where they can directly recognize infection or their antigens and then undergo clonal expansion.

Antibody Structure

An antibody molecule consists of four polypeptide chains: one pair of heavy chains on the interior and one pair of light chains on the exterior. The four chains are held together by disulfide bonds.

Each of the four chains has a constant region where the amino acid sequence is the same and a variable region where the amino acid sequence is unique. The constant segments of the heavy chains form the base of the antibody molecule.

The free tips of the two variable segments form the antigen binding sites of the antibody molecule. These sites can interact with an antigen in the same way that the active site of an enzyme interacts with a substrate. Small differences in the amino acid sequence of the variable regions affect the precise shape of the antigen binding site so that each antibody can demonstrate specificity.

When an antibody molecule binds to its corresponding antigen molecules, an antigen-antibody complex is formed.

Antibodies bind not to the entire antigen, but to specific portions of its exposed surface – regions called antigenic determinant sites.

A complete antigen is an antigen with at least two antigenic determinant sites, one for each of the antigen binding sites on an antibody molecule.

A partial antigen, or haptens, does not ordinarily cause B-cell activation. However, they may become attached to carrier molecules, forming combinations that can function as complete antigens.

There are five different classes of antibodies, or immunoglobulins (Igs). The classes are determined by differences in the structure of the heavy-chain constant regions and so have no effect on the antibody’s specificity, which is determined by the antigen binding sites out on the variable region of the chains.

1. IgA– a dimer found primarily in glandular secretions such as mucus, tears, saliva, breast milk, sweat, and semen. These antibodies attack the pathogens before they gain access to internal tissues.
2. IgD– a monomer found on the surface of B-cells where it can bind antigens in the extracellular fluids. This binding plays a role in the sensitization of the B cell so that it proliferates to form the clone army.
3. IgE– a monomer that attaches as an individual molecule to the exposed surfaces of basophils and mast cells which initiate the inflammatory response via histamine and heparin.
4. IgG– account for 80% of all antibodies. IgG antibodies are responsible for resistance against many viruses, bacteria, and bacterial toxins. IgG are monomers and can cross the placenta. IgG antibodies cause the effects of HDN, hemolytic disease of the newborn, discussed in chapter 17.
5. IgM–a pentamer secreted after an antigen is encountered. IgM concentrations decline as IgG production accelerates. The anti-A and anti-B antibodies responsible for the agglutination of the incompatible blood types are IgM antibodies.

Sensitization and Clonal Expansion of B-lymphocytes:

When a B-lymphocyte encounters its specific antigen in the body fluids, it prepares to undergo activation. This preparatory process is called sensitization.

The activated B-lymphocytes begin to proliferate rapidly forming a “clone” army. This initial response to exposure to an antigen is called the primary response. Because the antigen must activate the appropriate B-cells, the primary response takes time to develop. During the primary response, the antibody titer, or level of antibody activity in plasma, does not peak until one to two weeks after the initial exposure.  

As the B-cell clones mature, they differentiate into two types of cells:

Plasma B-cells – secrete free antibodies that attack the current infection and/or the antigens of the infection. After the infection is defeated, plasma cells undergo apoptosis, or programmed cell death. The antibodies secreted by the plasma cells (which can be as many as 100 million antibodies per hour) remain in circulation for an extend amount of time after the infection is over.

Memory B-cells – remain in reserve and are primed to respond quickly to subsequent exposures to infections with the same antigens. The next time you encounter the same infection, memory B-cells generate a faster and more efficient response. This is called the secondary response. In the secondary response, antibody titers increase more rapidly and reach levels many times greater than they did in the primary response. The secondary response is triggered even if the second exposure occurs years after the primary exposure.

Humoral immunity can be actively or passively developed.

ACTIVE: a person makes their own antibodies giving them long-term immunity

Naturally acquired active immunity – a person makes their own antibodies in response to a natural exposure to antigens in the environment. Example: getting chicken pox from your classmate.

Artificially acquired active immunity – develops after administration of an antigen to purposely expose someone to antigen. Administration of the antigen stimulates the immune system to make antibodies against the infection. Example: vaccinations.

PASSIVE: antibodies are generated by someone or something else which provides short-term immunity.

Naturally acquired passive immunity – a person receives antibodies from another person by participating in a natural activity. Example: an infant getting antibodies from their mother through breast milk.

Artificially acquired passive immunity – antibodies produced by someone else are purposely given to the person to provide immunity. Example: anti-venom or gamma globulin,

The Immune Response Against Pathogens

Antibodies use many different mechanisms to destroy target antigens. Because each antibody can perform a different function, they are said to be versatile.

Complement activation – upon binding to antigen, portions of the antibody molecule change shape, exposing areas that bind complement proteins. The bound complement molecules then activate the complement system which destroys the antigen by lysis or enhancing phagocytosis.

Opsonization – antibodies can coat the surface of pathogens so the pathogens become “sticky” and are more susceptible to phagocytosis.

Phagocytosis – antigens covered with antibodies attract neutrophils, monocytes, and eosinophils – cells that phagocytize pathogens and destroy foreign or abnormal plasma membranes.

Precipitation and Agglutination – if antigens are close together, an antibody can bind to antigenic determinant sites on two different antigens. In this way antibodies can clump large numbers of antigen together. When the target antigen is on the surface of a cell or virus, the process is called agglutination. When the target antigen is non-cellular, the clumping is called precipitation.

Neutralization – both viruses and bacterial toxins must bind to the plasma membrane of body cells before they can enter or injure those cells. Antibodies can block the binding sites so the viruses or toxins cannot bind to the body cells. This is called neutralization.

Prevents pathogen adhesion – antibodies dissolved in saliva, mucus, sweat, and tears coat epithelial cells, providing an additional layer of defense. A covering of antibodies makes it difficult for bacterial and viruses to adhere to penetrate body surfaces.

Inflammation – antibodies may promote inflammation by stimulating the release of histamine and heparin from basophils and mast cells.

Immune System Disorders

Immunodeficiency= deficient numbers of immune system cells

Severe combined immunodeficiency (SCID) syndrome is a congenital condition that results from a genetic disorder leading to deficits in both B and T cells.

Acquired immune deficiency syndrome (AIDS) is caused by the Human immunodeficiency virus (HIV) is a condition that destroys the helper T cells thus depressing cell-mediated immunity. Most patients die of opportunistic infections such as the flu or pneumonia.

Allergies occur when the antibody response is so severe it causes tissue damage as it fights off a perceived infection, or allergen, that would otherwise be harmless to the body (such as pollen or pet dander).

Immediate hypersensitivity (Type I)

=begins within seconds of exposure and lasts half to one hour. Example: anaphylactic shock and allergic rhinitis

Subacute hypersensitivity (Type II – III)

=onset is 1-3 hours after exposure and the duration is 10-15 hours. Example: Type II = such as transfusion of mismatched blood and Type III =farmer’s lung.

Delayed hypersensitivity (Type IV)

=occurs within 1-3 days and lasts for a week or more.Example: Contact dermatitissuch as poison ivy and the tuberculosis skin test

Autoimmune disease occurs B cells make antibodies against normal body tissues. These misguided antibodies are called autoantibodies.

There are numerous autoimmune diseases:

Multiple sclerosis–autoantibodies attack white matter of the nervous system leading to demyelination of neurons which can cause weakness or even paralysis.

Rheumatoid arthritis – autoantibodies destroythe connective tissues associated with joints or the joint capsules.

Systemic lupus erythematosus–autoantibodies attackmany organs

Grave's disease–autoantibodies attack thyroid tissue causing an excessproduction of thyroxine.

Type I diabetes mellitus–also known as insulin-dependent diabetes mellitus (or IDDM), autoantibodies attack the pancreatic cells that produce insulin.

Glomerulonephritis–autoantibodies attack the kidneys leading to renal dysfunction.

Myasthenia gravis – attack ACh receptor at neuromuscular junctions leading to debilitating muscle weakness

Transplantation and Cancer Immunology

Graft Rejection

Result from tissues, organs, or blood transplants that are not compatible with the tissues of the recipient. They are recognized as non-self and attacked.  

In order to reduce rejection, the best possible match is sought and immunosuppressivedrugs are used.

1. Autografts=tissues from the same person
2. Isografts=tissues from genetically identical twins
3. Allografts=tissues from non-genetically identical persons
4. Xenografts=tissues from organisms of different species

CARDIOVASCULAR SYSTEM-Heart and Blood vessels

THE HEART

It is a muscular organ responsible for pumping blood around the body. Lies within the pericardial cavity. Has four chambers. 

1. Heart wall consists three layers:
2. Endocardium like tunica intima-inner layer
3. Myocardium-Cardiac muscle-middle layer
4. Epicardium like the tunica adventitia-outer layer

Papillary muscles together with Chorda tendinea connects the cuspids with myocardium

Shape: the heart is pear shaped

Location: located in the middle Mediastinum. It extends from second to fifth intercostal spaces. The apex beat is located in the intersection of 5th intercostals space and mid-clavicular line

Sulci=coronary sulcus circles the heart, separating the atria from ventricle. Anterior and posterior sulci separate the two ventricles. Anterior sulcus is on the anterior surface while posterior is on the diaphragmatic surface of the heart

Pericardium

It is a fibrous sac surrounding the heart and the roots of great vessels. It consists of fibrous pericardium and serous pericardium

Fibrous pericardium is a tough connective tissue outer layer that defines the boundaries of the middle mediastinum

 Serous pericardium is thin and consists of

• Parietal layer that lines the inner surface of the fibrous
• Visceral layer that adheres to the heart and forms its outer covering

The parietal and visceral layers are continuous at the roots of the great vessels. The space between the parietal and visceral layers is called pericardial cavity and contains serous fluid that lubricates the heart.

The fibrous pericardium is attached inferiorly to the central tendon of the diaphragm, and anteriorly to the sternum through sternopericardial ligaments

Heart chambers and valves

4 in number two ventricles, 2 atria= right and left

4 valves; tricuspid between right atrium and ventricle; bicuspid between left atrium and ventricle; semilunar= aortic between left ventricle and aorta; pulmonary between pulmonary trunk and right ventricle 

Blood supply-arterial

Blood supply to the heart is from the right and left coronary arteries which are branches of the ascending aorta. The left coronary artery branches into anterior interventricular artery and circumflex artery. The circumflex artery give rise to left marginal artery. The right coronary artery give rise to sino atrial node branch, right marginal artery and posterior interventricular artery. Blockage of coronaries and any of their branches leads to myocardial infarction which may progress to cardiac arrest

Venous

Great cardiac vein accompanies anterior interventricular artery and circumferex artery to drain into coronary sinus. The middle cardiac vein accompanies the posterior interventricular artery to drain into coronary sinus. Small cardiac vein accompanies right coronary artery to drain into coronary sinus. Right marginal vein drains into small cardiac vein. Coronary sinus located in the posterior surface of the heart drains into the right atrium.

ARTERIAL SYSTEM OF THE HEART

VENOUS DRAINAGE

Anterior view

Posterior view

BLOOD VESSELS

Blood vessels are of three types: arteries, veins and capillaries.

Walls

• Tunica intima Endothelium
• Tunica media Muscle layer=middle layer
• Tunica adventitia Outer supporting tissue=outer layer

The walls of large of vessels can not be sustained by diffusion of nutrients from their lamina and are thus supplied by small arteries called vasa vasorum (ie vessels of vessels) which are derived from either from the main vessel itself or from adjacent arteries. 

Arteries have thickest wall especially the muscle layer. Capillaries lack muscle.

Arteries

Transport blood from the heart and distribute it to the various tissues of the body by means of their branches.  

And the smallest arteries, <0.1mm in diameter, are referred to as arterioles.  

The joining of branches of arteries is called an anastomosis. Arteries do not have valves  

Body arterial system

Aorta= arises from left ventricle. It consists of ascending, the arch and the descending aorta. The descending aorta has thoracic and abdominal parts

Ascending aorta gives rise to the right and left coronary arteries

Branches of aortic arch

 1) Brachiocephalic trunk which then gives rise to the right internal carotid artery and right subclavian artery.

2) left internal carotid artery and left subclavian artery

Branches of thoracic aorta

• Bronchial arteries to the lungs
• Esophangeal arteries to esophagus
• Posterior intercostals branches to the thoracic wall
• Superior phrenic branches to the diaphragm

Branches of abdominal aorta

• Inferior phrenic arteries to the diaphragm
• Celiac trunk that gives branches to the stomach, spleen and commom hepatic branch
• Supra renal and renal branches to adrenal and kidneys respectively
• Superior mesenteric to the small intestine and upper colon
• Gonadol arteries to the gonads
• Inferior mesenteric to lower colon and rectum

Terminates as left and right common iliac arteries which then branches as internal external iliac arteries. Internal iliac supplies the pelvic cavity and perineum contents and gluteal region while external iliac enters the lower limb as femoral artery to supply lower limb

Subclavian arteries

Gives several branches to the thorax and neck and exit the neck posterior to first rib to become axillary artery. The axillary artery enters the arm as brachial artery. 

The brachial artery terminates as radial and ulnar arteries in the cubital fossa

Internal carotid

In the neck divides into internal and external carotids. Internal enters the cranium to supply the brain. The other major supplier to the brain is the vertebral artery, a branch of subclavian which enters the cranium through foramen magnum. External carotid supplies the neck, facial region and anterior scalp.

Branches of external carotid are superior thyroid, pharyngeal, occipital, lingual facial, maxillary and ascending superficial artery

Veins 

Are vessels that transport blood back to the heart; many of them posses valves. The smallest veins are called venules. The smaller veins, or tributaries, unite to form venous plexuses. Medium-size deep arteries are often accompanied by two veins, one on each side, called venae comitantes.

Main veins

The main veins of the body are inferior and superior vena cava, internal jugular, subclavian, brachiocephalic, femoral, iliac, azygous and portal veins

Internal jugular draining the head, face and neck join the subclavian (which drains the upper limb) in the lower neck to form brachiocephalic vein.

Left and right brachiocephalic join in the upper thorax to form superior vena cava which drains into right atrium

The left and right common iliac join to form inferior vena cava that drains into the right atrium 

Femoral vein draining the lower limb becomes external iliac vein after crossing into the body trunk

Veins leaving the gastrointestinal tract do not go directly to the heart but converge on the portal vein to drain into the liver. Hepatic veins drains the liver and emphties into inferior vena cava

Branches of bdominal aorta are accompanied by corresponding veins

Azygous vein and accessory azygous vein formed by ascending lumber veins and subcostal veins drains the thoracic cavity. Accessory join azygous which drains into superior vena cava

There are no veins in the brain, instead there are sinusoids 

Capillaries Are microscopic vessels in the form of a network connecting the arterioles to the venules.

INTRINSIC CODUCTING SYSTEM OF THE HEART

The conducting system of the heart is initiated in the sino atrio node. The wave travels in the wall of atria ans reaches atrio-ventricular node. 

From atrio-ventricular node, conduction is through atrioventricular bundle(bundle of His) passing through interventricular septum. In the upper interventricular septum, the bundle of His divides into the right and the left bundles which passes through the interventricular septum and eventually distributes to the walls of the heart as Purkinje fibers. Autonomic nervous system influence the rate of heart beat

Revision questions:

• Describe the structure and function of lymphatic system and its relationship to blood vessels and to the immune system.
•  
• Identify the variety of lymph vessels, describe the areas of the body they drain, and explain lymphedema.
•  
• Identify the classes of lymphocytes, discuss their importance, and describe their distribution in the body.
•  
• Describe the structure and function of peyer’s patches, MALT, the appendix, and tonsils.
•  
• Describe the structure and function of the lymph nodes, thymus, and spleen.
•  
• Trace the path of lymph through a lymph node.
•  
• Explain how physical barriers and phagocytes play a role in innate or non-specific defenses.
•  
• Describe the immunological surveillance and explain the role of NK cells.
•  
• Describe the various types of interferons and their functions.
•  
• Explain the alternate and classical pathways of complement activation.
•  
• Explain the significance of inflammation and fever as innate defenses.
•  
• Describe the differences between innate defenses and adaptive defenses.
•  
• Explain how antigens trigger an immune response by way of MHC Class I and Class II proteins.
•  
• Explain the events of antigen recognition and the roles of CD markers and cell differentiation.
•  
• Explain the sensitization and activation of B cells and the role of plasma cells.
•  
• Describe the structure of an antibody, discuss the types of antibodies in the body, and explain the primary and secondary responses to antigen exposure.
•  
• Explain the many mechanisms by which antibodies destroy antigens.
•  
• Describe the processes of clonal expansion of B-cells and T-cells.
•  
• Compare and contrast the immune response against bacterial infections versus viral infections.
•  
• Describe the disorders common to the lymphatic and immune systems.
•  
• Describe the structure and function of lymphatic system and its relationship to blood vessels and to the immune system.
•  
• Identify the variety of lymph vessels, describe the areas of the body they drain, and explain lymphedema.
•  
• Identify the classes of lymphocytes, discuss their importance, and describe their distribution in the body.
•  
• Describe the structure and function of peyer’s patches, MALT, the appendix, and tonsils.
•  
• Describe the structure and function of the lymph nodes, thymus, and spleen.
•  
• Trace the path of lymph through a lymph node.
•  
• Explain how physical barriers and phagocytes play a role in innate or non-specific defenses.
•  
• Describe the immunological surveillance and explain the role of NK cells.
•  
• Describe the various types of interferons and their functions.
•  
• Explain the alternate and classical pathways of complement activation.
•  
• Explain the significance of inflammation and fever as innate defenses.
•  
• Describe the differences between innate defenses and adaptive defenses.
•  
• Explain how antigens trigger an immune response by way of MHC Class I and Class II proteins.
•  
• Explain the events of antigen recognition and the roles of CD markers and cell differentiation.
•  
• Explain the sensitization and activation of B cells and the role of plasma cells.
•  
• Describe the structure of an antibody, discuss the types of antibodies in the body, and explain the primary and secondary responses to antigen exposure.
•  
• Explain the many mechanisms by which antibodies destroy antigens.
•  
• Describe the processes of clonal expansion of B-cells and T-cells.
•  
• Compare and contrast the immune response against bacterial infections versus viral infections.