Patho midterm – final 2017 – Flashcards

First, the patient should take some comfort in the fact that his tumor is benign. A malignant tumor of the same origin would be a hepatocellular adenocarcinoma. Benign tumors have the following characteristics: slow growth, well-defined capsule, less invasive, well-differentiated, low mitotic index, and do not metastasize. Malignant tumors tend to grow rapidly, lack encapsulation and differentiation, invade local structures, have a high mitotic index, and spread to distant locations through the bloodstream or lymphatics.

Chronic inflammation causes cancer by releasing compounds such as reactive oxygen species that promote mutations.

Chronic inflammation increases the relative risk for many cancers. Toxins released from cigarettes inflame and damage respiratory tissue. Crohn disease can cause extensive chronic inflammation anywhere in the gastrointestinal tract. Working as a farmer requires many days out in the sun. The farmer probably has not had a sunburn in years, but frequent sunburn is not a prerequisite for skin cancer. As was discussed in previous chapters, the inflammatory process causes release of compounds such as reactive oxygen species and molecules that can promote mutations and block the cellular response to DNA damage.

Symptoms of polycythemia vera are mainly the result of increase blood viscosity.

A characteristic of cancer in situ is that cells remain localized in the glandular or squamous cells.

Oncogenes are Genes that have undergone mutation that direct the synthesis of protein to accelerate the rate of tissue proliferation Hormones, enzymes, antigens, and antibodies produced by cancer cells are tumor cell markers.

The PSA is a protein produced by the cells of the prostate gland. The PSA test measures the level of PSA in the blood. The PSA test is reported in nanograms per milliliter (ng/ml). It is normal for men to have low levels of PSA in their blood. There is not a specific normal or abnormal level of PSA. PSA levels can increase as a result of prostate cancer or benign prostate conditions. Some of the more common benign prostate conditions are prostatitis and benign prostatic hyperplasia. However, the higher a man's PSA level, the more likely prostate cancer is present. PSA levels alone do not give physicians enough information, but physicians will take the PSA result into account when deciding whether to check further for signs of prostate cancer.

Glucose 6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell disease are both disorders that are initiated by hypoxemia and acidosis.

When patients who have lung cancer develop Cushing syndrome it is an example of a paraneoplastic syndrome.

Hypercalcemia is an electrolyte imbalance that accompanies multiple myeloma?

A requirement for localized spread of cancerous cells is angiogenesis. Once tumor cells grow beyond a few millimeters, simple diffusion of oxygen does not provide enough nutrients to meet the needs of the growing cells. More advanced cancer cells can secrete angiogenic factors that activate a cascade of mediators to form new vasculature and provide nutrients to the tumor. With these resources, the tumor can now continue to expand.

Cancers arising from connective tissue usually have the suffix sarcoma. Cancers of lymphatic tissue are called lymphomas, whereas cancers of blood-forming cells are called leukemias. Carcinoma is a cancer of epithelial tissue.

Catecholamines are secreted by the adrenal medulla and are found in excess if a tumor exists. PSA levels are used to detect prostate cancer. AFP is used to detect liver and germ cell cancers. ACTH is the marker used to detect pituitary adenomas.

Because subsequent generations were not affected by the cellular mutations, it can be concluded that primarily the somatic cells were affected. If the germ cells were affected, serious congenital conditions would likely have been a result.

Cancer confined to the organ of origin is stage 1; cancer that is locally invasive is stage 2; cancer that has spread to regional structures, such as lymph nodes, is stage 3; and cancer that has spread to distant sites, such as a liver cancer spreading to the lung or prostate cancer spreading to bone, is stage 4. The prognosis generally worsens with increasing tumor size, lymph node involvement, and metastasis. Benign tumors do not spread to distant regions.

Cancer development involves multiple stages including initiation, promotion, and progression. This theory best explains cancers in adults with a 20+-year latency period. In the initiation stage, there is rapid, irreversible altering or mutation of DNA that occurs after a single exposure to a carcinogen (initiator). There must be a strong enough dose or exposure to cause DNA change. In this case, the patient was most likely exposed to ionizing radiation as a child—perhaps inadvertent exposure because of his father's occupation. After this initiation stage, the cells stay dormant in G0 phase or, if dividing, produce very small numbers of transformed daughter cells. The initiated cells are not considered cancerous until a promoting agent acts on them over time to produce an altered, autonomous phenotype. In the promotion stage, promoters induce tumor development. These promoters can be hormones; chemical agents such as drugs, chemicals, tobacco, and plant products; or environmental factors such as air pollution, occupation, diet, and ultraviolet (UV) radiation. For promoters to induce tumor development, there must be time-dependent repeated exposures to the promoters or prolonged exposure over a period of time. Promoters interfere with differentiation and maturation, activating the transformed cell to go through mitotic division, and continue to go through replication phases. In the early stages, the effects of promoters can be reversible. In this case, the patient had a number of possible promoters that contributed to his cancer, including smoking, alcohol use, occupational exposure to fine dust particles, chronic exposure to -radiation, a high-meat and high-fat diet, and polycyclic hydrocarbons produced from charred, barbecued meat. In the progression stage, chromosomal abnormalities are in the cells. The greater the replications, the more the cell becomes abnormal. This leads to tumor development, invasion, and metastasis.

The spleen is not necessary for life or for hematologic function. However, several functions related to the spleen are impaired when it is removed. Leukocytosis occurs after the loss of the spleen, indicating that it may play a regulatory role in leukocyte production. Because the spleen has a role in the iron cycle, circulating iron levels decrease when the spleen is lost. Immune function also decreases when the spleen is absent, increasing infection risk. Antibody production diminishes, and old and defective blood cells that were previously removed by the spleen continue to circulate.

Adequate nutrition is necessary to provide the building blocks for erythropoiesis. This includes adequate amounts of protein, vitamins, and minerals. If nutrition is inadequate, the result is a slowing in the production of erythrocytes and subsequent onset of anemia. Protein plays a significant role in erythropoiesis. Inadequate available protein results in decreased erythrocyte production and shortened life span of those erythrocytes that are produced. In the absence of several vitamins, particularly B 12 and folate, erythropoiesis is halted.

Hemostasis involves a complex sequence of events. After injury, vasoconstriction or vasospasm constricts the bleeding vessels. This is followed by the formation of a platelet plug. The coagulation or clotting cascade is then activated and results in the formation of a blood clot. As the injury heals, clot retraction (which joins wound edges) and clot dissolution (fibrinolysis) occur.

Aspirin limits platelet aggregation and vasoconstriction by inhibiting synthesis of thromboxane A2, a prostaglandin. Thromboxane A2 is present in the dense granules of platelets and is released as the platelets begin clumping. By taking an aspirin, this decreases the chance of the platelets forming microclots.

The patient has secondary absolute polycythemia. Given the choice, hemoglobin prefers carbon monoxide over oxygen. As the patient smokes, the binding sites for oxygen are taken up by carbon monoxide. Because of the decreased oxygen-carrying capacity, the patient becomes hypoxic. The hypoxia is detected by the kidneys, erythropoietin is released, and more red cells are made to compensate for the lack of oxygen. The patient is now at risk for thrombus and embolus formation, heart failure, coronary artery disease, etc.

Both CGL and ALL are diseases of blood-forming organs causing growth of uncontrolled, undifferentiated, and immature lymphocytes (blast cells). These immature cells then circulate in the blood, infiltrating the liver, spleen, lymph nodes, and other tissue sites. The blood-forming cells affected by ALL and CGL are the lymphoid stem cells. Both CGL and ALL tend to occur in families, suggesting hereditary susceptibility. ALL affects primarily children. It is both an accumulation and a proliferation disorder in which a transformed mutation clones a line of poorly differentiated, abnormal daughter cells. These cells are unable to mature or respond to normal regulatory mechanisms. They also proliferate rapidly, which decreases or stops the proliferation of other cell lines in the bone marrow. ALL affects primarily either T cell or B cell lines. Anemia, thrombocytopenia, hemorrhage, and disseminated intravascular coagulation (DIC) usually accompany ALL. The gonads, bones, joints, central nervous system, kidneys, lungs, and gastrointestinal tract are the most common sites of infiltration. CGL affects primarily B cells in adults. The cells in CGL are slow growing and well differentiated. In CGL the B cells are unable to mature and synthesize immunoglobulin. Therefore individuals with CGL lack humoral immunity and have increased risk of infection, autoimmunity, and the development of secondary cancers. Anemia is usually mild, and hemorrhage is rare. Lymph node, liver, spleen, and salivary gland infiltration is common.

DIC is a cyclic disorder in which massive intravascular coagulation is triggered at the cellular level, producing microthrombi. The microthrombi block the microvascular system, using up clotting factors and platelets as well as causing widespread tissue ischemia. The development of widespread microthrombi formation at the cellular level also activates the fibrinolytic system, which attempts to rapidly lyse the clots. This process releases fibrin degradation or split products (FDP or FSP). The consumption of clotting factors and platelets along with the rising levels of FSP leads to inhibition of coagulation and bleeding. The bleeding with loss of vascular volume also contributes to tissue ischemia.

Children with Hgb S have a genetic hemoglobin mutation in which one amino acid, glutamic acid, is replaced by another amino acid, valine. When stressors such as dehydration, decreased PO2, or decreased pH occur, a sickling cycle follows. Systemic or local decreased PO2 (hypoxemia) causes Hgb S cells to form an elongated crescent shape because of reaggregation of hemoglobin into long chains. This shape causes the red blood cell membranes to become stiff, thus losing some of their capacity for active transport. In a hypoxemic state, sickling is further promoted in the microcirculation when hemoglobin releases oxygen to the tissues, and the microcirculation is clogged by sickled cells. This results in further stagnation and hypoxemia. Acidosis decreases hemoglobin's affinity for oxygen, causing more release of oxygen and contributing to sickling. Acidosis also causes less oxygen to be picked up by circulating hemoglobin in the lungs, further contributing to decreased PO2. Increased osmolality causes sickling because of resultant cellular dehydration and increased Hgb S content within the cells. Increased osmolality also causes sluggish blood flow, contributing to hypoxemia, vascular obstruction, and further sickling. In reversible sickle cells, the membranes will return to normal when the PO2 of the blood returns to normal. In irreversible sickle cells, the membranes stay in the elongated crescent shape because of calcium ion influx.

The flat portion of the curve at the top of the graph is sometimes called the arterial portion and represents partial pressure changes of oxygen between 60 and 100 mm Hg. Changes between these two values do not significantly affect the percent of saturation of hemoglobin. The steep part of the curve occurs after the partial pressure of oxygen drops below 60 mm Hg. It represents the rapid dissociation of oxygen from hemoglobin. During this phase there is rapid release of oxygen for diffusion into the cells. When the curve shifts to the left, hemoglobin has an increased affinity for oxygen and releases less to the tissues. Conditions that cause this include acute alkalosis, decreased PCO2, decreased temperature, low levels of 2,3-DPG, carboxyhemoglobin, methemoglobin, and abnormal hemoglobin. When the curve shifts to the right, hemoglobin has a decreased affinity for oxygen. Conditions that cause this include acute acidosis, high PCO2, increased temperature, high levels of 2,3-DPG, and abnormal hemoglobin.

The respiratory center in the brain stem controls respiration by transmitting impulses to the respiratory muscles, causing them to contract and relax. The respiratory center is composed of several groups of neurons located bilaterally in the brain stem: the dorsal respiratory group, the ventral respiratory group, the pneumotaxic center, and the apneustic center. The basic automatic rhythm of respiration is set by the dorsal respiratory group-a cluster of inspiratory nerve cells located in the medulla that sends efferent impulses to the diaphragm and inspiratory intercostal muscles. The dorsal respiratory group also receives afferent impulses from peripheral chemoreceptors in the carotid and aortic bodies and from several different types of receptors in the lungs. The ventral respiratory group, also located in the medulla, contains both inspiratory and expiratory neurons. It is almost inactive during normal, quiet respiration, becoming active when increased ventilatory effort is required. The pneumotaxic center and apneustic center, situated in the pons, do not generate primary rhythm but, rather, act as modifiers of the inspiratory depth and rate established by the medullary centers. Breathing can be modified by input from the cortex, the limbic system, and the hypothalamus, and the pattern of breathing can be influenced by emotion and by disease.

Epinephrine enhances sympathetic nervous system activity to counteract the effects of histamine on the airways. Stimulating the sympathetic system dilates airways and decreases airway resistance, thereby increasing ventilation.

Smoking causes inflammation. The resulting inflammation increases mucus secretion and swelling of the mucosa. Nicotine constricts the terminal bronchioles to increase airway resistance. Smoking also inhibits and destroys the respiratory cilia. This diminishes the body's ability to remove microbes and pollutants. These cellular changes combined with the carcinogens present in cigarette smoke lead to the increased risk of lung cancer.

Respiration is the exchange of CO2 for oxygen. Ventilation is the mechanical movement of gas or air into and out of the lungs and is often misnamed respiration. Circulation refers to the actual blood flow and oxygen delivery. Alveolar ventilation refers to the amount of air delivered to the alveoli.

Central chemoreceptors indirectly monitor arterial blood by sensing changes in the pH of the cerebral spinal fluid (CSF). Stretch receptors are located in smooth muscle and are sensitive to increases in the size or volume of the lungs. Irritant receptors are found in the epithelium of conducting airways and are sensitive to noxious aerosols, gases, and particles. J-receptors are located near the capillaries in the alveolar septa and are sensitive to increased capillary pressure.

Hyperpnea is rapid breathing. Orthopnea is difficulty breathing when an individual is lying flat. Dyspnea is difficulty breathing. Eupnea is normal respiratory rate and depth. Alternating periods of deep and shallow breathing and apnea characterize Cheyne-Stokes respirations. An increased ventilatory rate, large tidal volumes, and no expiratory pause characterize Kussmaul respirations. Hypoventilation is inadequate alveolar ventilation. Hyperpnea is rapid ventilation.

Clubbing, the bulbous enlargement of the distal segments of the fingers, is associated with disorders that cause hypoxemia like cystic fibrosis, bronchiectasis, pulmonary fibrosis, lung abscess, lung cancer, and congenital heart disease.

The most common cause of pulmonary edema is heart disease. Toxic gas inhalation, pulmonary hypertension, and ARDS are also causes of pulmonary edema but are not as common as pulmonary edema from heart disease.

Bronchiolitis is most common in children and is caused by a virus. It is an inflammatory obstruction of the small airways called the bronchioles. Bronchiolitis is observed in adults with chronic bronchitis.

Empyema is term used to describe the presence of pus in the pleural space and is a complication of respiratory infection. Abscess is a circumscribed area of suppuration and destruction of lung parenchyma. A consolidation is inflamed lung tissue that causes the alveoli to fill with exudate. Transudate is the presence of fluid with low protein content residing in the pleural space.

Increased bronchial smooth muscle spasm and increased vascular permeability contribute to asthma. Inflammation results in airway hyperresponsiveness. Increased bronchial smooth muscle spasm and increased vascular permeability are features of asthma. Asthma is an immunoglobulin E (IgE)-mediated response.

The hypersecretion of mucus with a chronic productive cough that lasts for at least 3 months for a minimum of 2 consecutive years characterizes chronic bronchitis. The mucus is thicker and will adhere to embedded bacteria. This condition is increased up to 20 times in smokers.

Pseudomonas aeruginosa is commonly acquired in hospitals or nursing homes.

Group A beta-hemolytic Streptococcus often causes peritonsillar abscess, which results in unilateral pharyngeal swelling, fever, sore throat, dysphasia, trismus, and pooling of saliva. Cervical lymphadenopathy is often observed on the same side. Diphtheria causes sore throat and dysphagia. Bilateral swelling of the tonsils is usually involved, with a tenacious membrane covering the mucosa. Diphtheria is not common because of immunization. Croup is caused by a virus and generally produces a barking cough. Generally, bacteria cause epiglottitis with accompanying high fever, drooling, and inspiratory stridor. Epiglottitis is also declining because of immunization.

Most commonly (85% of the time), parainfluenza causes laryngotracheobronchitis and has the highest incidence in late fall and winter. It is also more common in boys. The peak age of occurrence is 1 to 2 years of age, and the age range is 6 months to 5 years.

Haemophilus influenzae and Streptococcus pneumoniae are bacteria that become embedded in the airway secretions in chronic bronchitis?

Pulmonary edema and pulmonary fibrosis cause hypoxemia by impairing diffusion through the alveolar-capillary membrane.

In transudative pleural effusion, the fluid is watery and diffuses out of the capillaries as a result of increased blood pressure or decreased capillary oncotic pressure. An exudative effusion is less watery and contains white blood cells and plasma proteins. It occurs in response to inflammation, infection, or malignancy and involves inflammatory processes that increase capillary permeability.

Cystic fibrosis is a pulmonary disorder involving an abnormal expression of a protein producing viscous mucus that obstructs the airways, pancreas, sweat ducts, and vas deferens.

Upper respiratory infection

Viruses

Pneumocystis jiroveci

Interstitial pneumonia

Granuloma formation

Emphysema

Cigarette smoking

Exercise

T helper lymphocytes

Pneumoconiosis

Hypertension

B. Tracheotomy is the most common treatment - false

Flattening of the diaphragm due to hyperinflation

Formation of granulomas

Streptococcus pneumoniae

Asthma

Viruses

Causes accumulation of arachidonic acid.

Taper symmetric subglottic narrowing on xray

Emphysema

In type I diabetes mellitus, the b cells in the islets of Langerhans are destroyed. This destruction is progressive and associated with the presence of IgG islet cell antibodies (ICA), suggesting an autoimmune process. At the clinical onset of the disease, 80% to 90% of all insulin-secreting b cells in the islets of Langerhans are destroyed, leaving a small number of little, atrophic, and fibrotic cells. Within 1 year, all remaining cells are destroyed. Coinciding with b cell destruction, a cell function is abnormal, resulting in excess glucagon production. Therefore the functional deficit in type I diabetes mellitus is both a lack of insulin production and an excess of glucagon production. The cause of this destructive process has been theorized to include a viral disease, an immune reaction, or inherited susceptibility combined with environmental factors. In all likelihood, type I diabetes mellitus may be a combination of all these factors. The autoimmune process may be triggered by viral infection such as coxsackie B4 virus or mumps. This is highly supported by the increased incidence of type I diabetes in the fall and winter in the Northern Hemisphere when there are increased viral infections. Type I diabetes mellitus may also be linked genetically. There is an association between type I and HLA-D and HLA-DR alleles-particularly HLA-DR3 and HLA-DR4. In type II diabetes mellitus, the cellular changes are more nonspecific. Islet cells are progressively replaced with hyaline tissue, an albuminoid substance, leaving a decrease in the size and number of b cells. Also, fatty infiltration is present in both the liver and pancreas, causing increased tissue size and the presence of glycogen vacuoles. However, the ratio of a : b cells in the pancreas is normal and the plasma and pancreatic levels of insulin are not decreased. Many of these changes are similar in aging persons both with and without type II diabetes mellitus. According to the World Health Organization (WHO), the strongest risk factor for the development of type II diabetes mellitus is obesity. Type II diabetes mellitus has been theorized to include genetic susceptibility combined with obesity. The causes have been thought to involve insulin receptors in the plasma membrane and insulin resistance. One theory advocates that a decreased number of insulin receptors cause decreased insulin binding. Another theory states that intracellular events after insulin receptor binding are altered. Several theories explore the relationship between hyperinsulinemia and type II diabetes mellitus. One of these theories suggests that the islet cells "give out" over time in an effort to produce enough insulin to compensate for obesity. Another states that hyperinsulinemia causes cellular insulin resistance to protect against hypoglycemia. Therefore the functional deficit in type II diabetes mellitus is a combination of obesity, increased insulin resistance, and an excess of glucagon production.

Mr. Jones has diabetes insipidus, which has three forms: neurogenic, nephrogenic, and psychogenic. The neurogenic form is caused by a hypothalamic, infundibular stem, or posterior pituitary problem, that decreases or inhibits antidiuretic hormone (ADH) synthesis, transport, or release. This may be caused by pituitary tumors, brain tumors, infections, immunologic problems, or thrombotic problems. The nephrogenic form of diabetes insipidus may be acquired, permanent, or reversible. It is caused by renal tubule insensitivity to ADH. In this form the amounts of ADH are normal but the tubules are no longer able to respond to the hormone. Examples of renal problems that can lead to diabetes insipidus include pyelonephritis, amyloidosis, destructive uropathies, and polycystic kidney disease. It may also be secondary to anesthetic drug use and the use of lithium carbonate. The psychogenic form of diabetes insipidus is caused by compulsive water drinking by individuals with psychiatric disorders. In this form the individual has periodic polyuria, high urine volume, and plasma osmolarity of less than 285 mOsm/kg

There are several causes of primary hypothyroidism. Three result in a greater than 95% spontaneous recovery: • Subacute thyroiditis—is a nonbacterial inflammation of the thyroid gland often preceded by a viral infection. Symptoms include fever, tenderness and enlargement of the thyroid gland, elevated levels of thyroid hormone initially as thyroid hormone stores are released because of inflammation, and hypothyroidism as the gland recovers. Symptoms may last 2 to 4 months and are treated with nonsteroidal anti-inflammatory drugs (NSAIDs), beta-blockers, and, if needed, thyroid hormone supplementation. • Painless thyroiditis—has a course similar to subacute thyroiditis but is pathologically identical to Hashimoto disease. • Postpartum thyroiditis—generally occurs within 6 months of delivery, occurs in up to 7% of all women, and shares a course similar to subacute thyroiditis. It is related to Hashimoto disease. Several mechanisms result in destruction of the thyroid gland leading to hypothyroidism: • Hashimoto disease—an autoimmune thyroiditis that results in destruction of thyroid tissue by circulating thyroid antibodies and infiltration of lymphocytes. It has a genetic predisposition. • Radioiodine ablation—deliberate destruction of the thyroid gland caused by radioiodine, a treatment for hyperthyroidism. • Thyroidectomy—deliberate removal of the thyroid gland, a treatment for hyperthyroidism and thyroid cancer. • Medications (lithium and amiodarone)—inadvertent destruction of the thyroid is an adverse effect/side effect of medications.

Diabetes is the term used for any of several metabolic disorders marked by persistent thirst and excessive urination. The specific gravity results of these two people are perfect examples of diabetes insipidus and diabetes mellitus. Diabetes insipidus is caused by insufficient or a decreased response to ADH. By not responding to ADH, the renal system excretes increased amounts of dilute urine. Diabetes mellitus is related to carbohydrate metabolism. Person B is excreting large amounts of urine because of the excessive glucose and possibly ketone excretion. The increased solutes encourage water loss from the renal system, but because the solutes are present in such high amounts, the specific gravity result is increased.

Coming to the PCP with a fasting blood sugar of 110 mg/dl does not give the whole story in this situation. The man seems to be representing great glycemic control, but many proteins can react with carbohydrates at the peptic N-terminus forming glycosylated peptides. Glucose and hemoglobin react in such a fashion to form a stable glycosylated hemoglobin product. Remember that red cells have a life span of about 120 days. Changes to the red cells can give PCPs a better understanding of a person's glycemic control. The higher the blood glucose, the more glycosylated hemoglobin is formed. Although it is method dependant, hemoglobin A1c concentrations of 5% to 7% are within the normal range of most methods. Values greater than 12% demonstrate poor glycemic control. So this man should be reprimanded for achieving good glucose control only on the day he knew he was visiting his PCP.

Increased fluid intake decreases the secretion of ADH, so fluid output increases. In addition, alcohol inhibits ADH secretion, so even more fluid is lost through urine output. The combination of these two will lead to dehydration. Once the effects of the alcohol decrease, aldosterone and ADH secretion increases to conserve water and increase thirst until water balance is restored.

The pituitary gland is susceptible to ischemia and infarction because it is extremely vascular. With brain trauma, this affects the blood flow, causing an infarction that could lead to necrosis and fibrosis of the tissue in the pituitary. Afterward, the gland begins to swell, further hindering the blood supply of the pituitary.

Diagnostic tests include an oral glucose test and monitoring the suppression of the growth hormone and the elevated insulin-like growth factor 1 (IgF-1) levels. Treatment options include removing the GH-secreting adenoma by transsphenoidal surgical excision,, radiation therapy if the rapid control of the levels of GH isn't essential or the person is not healthy enough for surgery, or if hyperfunction continues after subtotal resection. In addition, analogs such as octreotide, octreotide LAR, and lanreotide may be productive in helping to lower levels of the growth hormone. Lastly, pegvisomant has been proven to be an effective drug to influence tissue insensitivity to growth hormone.

Graves' disease is considered an autoimmune disease that results in hyperthyroidism, which is caused by thyroid gland stimulation. Due to the hyperfunction of the thyroid gland, iodine uptake is significantly increased along with the metabolism of the thyroid gland, which may be the cause of hypervascularity and gland enlargement (goiter). There is also a large increase in T3 production which plays a role in thyroid gland hyperstimulation. Cushing disease is the result of an exorbitant secretion of ACTH from the anterior pituitary gland. This disease always has an excessive level of cortisol. Most of the individuals who suffer Cushing disease have a pituitary microadenoma that secretes ACTH.

Addison disease is an autoimmune disease that affects women more than men. It is considered a somewhat rare disease that occurs mainly from ages 30 to 60. The autoimmune destruction of the adrenal cortex is the most common cause. Characteristics of Addison disease include elevated serum ACTH levels and corticoid synthesis and output insufficiency.

TSH secretion is regulated by thyrotropin-releasing hormone, primarily in the hypothalamus and by negative feedback inhibition from thyroid hormones. Increased anterior pituitary release of TSH stimulates the secretion of thyroid hormones. TSH is inhibited by thyroxin (T4).

The internal structure of the bone is maintained by remodeling. The process is carried out by basic multicellular unitsclusters of bone precursor cells that differentiate into osteoclasts and osteoblasts. They are located on the free surfaces of bones and along the vascular channels, especially the marrow cavities. In a three-phase process, which takes about 4 months to occur, existing bone is resorbed and new bone is laid down to replace it. In phase 1 (the activation phase), a stimulus activates bone precursors in a localized area of bone to form osteoclasts. In phase 2 (the resorption phase), osteoclasts form a cutting cone, resorb bone, and leave behind an elongated cavity. This resorption cavity follows the longitudinal axis of the Haversian system in compact bone. In spongy bone it parallels the surface of the trabeculae. In phase 3 (the formation phase), new bone (secondary bone) is laid down by osteoblasts lining the walls of the resorption cavity. Successive layers (laminae) in compact bone are laid down until the resorption cavity is reduced and a new, narrow Haversian canal around a blood vessel is formed. New trabeculae are formed in spongy bone. The remodeling process can repair microscopic bone injuries, but larger injuries heal by the same five stages as soft tissue injuries. New bone instead of scar tissue is the result. Hematoma formation occurs if vessels have been damaged and hemorrhage has occurred. Fibrin, platelets, and hematopoietic growth factors within the hematoma form a meshwork that is the initial framework for healing. This is followed by procallus formation, in which fibroblasts, capillary buds, and osteoblasts move into the wound and produce granulation tissue called procallus. Cartilage is formed as a precursor to bone, and types I, II, and III collagen are formed. This stage is followed by callous formation, in which osteoblasts in procallus form membranous or woven bone, namely callus. Enzymes cause the deposition of calcium and phosphorus, which harden the bone. The next phase is callus replacement, in which osteoblasts replace the callus with lamellar or trabecular bone. In the last phase (remodeling), periosteal and endosteal surfaces of bone are remodeled to the size and shape of the bone before injury. The length of time for this entire process depends on the extent of injury and the physiologic resources of the patient for healing but can take as long as 4 years to complete.

In fibrous joints, bone is connected directly to bone by fibrous cartilage. These joints are generally synarthroses (immovable joints), but they may allow some movement depending on the flexibility of the fibrous connective tissue. They are subdivided into three types: sutures (located between skull bones in children), syndesmoses (radius and ulna), and gomphoses (teeth within the maxilla or mandible). Cartilaginous joints are symphyses and synchondroses. A symphysis is a cartilaginous joint in which bones are united by a pad or disk of fibrocartilage and covered by a thin layer of hyaline cartilage. The intervertebral disks are examples of this type of joint. Synchondroses are joints in which hyaline cartilage, rather than fibrocartilage, connects the two bones. Examples are the joints between the ribs and the sternum. Synovial joints (diarthroses) are the most movable and most complex joints in the body. They consist of a fibrous joint capsule, a synovial membrane that lines the inner surface of the joint capsule, a joint cavity, synovial fluid that fills the joint cavity and lubricates the joint surface, and articular cartilage that covers and pads the articulating bony surfaces. Movement can be uniaxial (elbow), biaxial (finger), or multiaxial (hip). Types of movement include circumduction, extension, supination, pronation, adduction, abduction, flexion, hyperextension, extension, hyperflexion, rotation, dorsiflexion, plantar flexion, inversion, and eversion.

Changes in joints include development of osteoarthritis as a result of life-long wear and tear, shortened ligaments and loss of flexibility, thinning of articular cartilage, and diminished production of synovial fluid. If the bone surfaces become exposed, spurs can form and the synovial membrane can become inflamed.

Creatine kinase provides a high-energy bond that can be added to ADP as needed. Anaerobic glycolysis catabolizes glucose into two molecules of pyruvic acid, thus providing two net ATP per glucose molecule. Mitochondria oxidize pyruvic acid to CO2 and H2O through aerobic cellular respiration. This process releases about 36 ATP per glucose molecule.

The pectoral girdle is designed more for mobility than strength. The acetabulum is deeper than the glenoid fossae. The neck of the femur is longer and more angled than the neck of the humerus. The pelvic girdle is attached to the vertebral column and thus more stable than the pectoral girdle.

Hematoma formation is the first stage. It is characterized by bleeding that forms a clot between the medullary canals of the bone ends and beneath the periosteum. With the necrosis of bone cells at the fracture site and the bleeding, an inflammatory reaction results. This leads to invasion of the site by inflammatory cells and osteoclasts that remove dead bone. The fracture site changes from a clot to an organized fibrin network with invasion of vascular tissue that increases blood supply to the area. Cells in the periosteum, endosteum, and bone marrow produce new bone beginning along the outer surface of the bone and moving over the fracture site. The osteoblasts synthesize a collagen matrix that becomes calcified. Remodeling occurs to remove excess callus (woven bone) and form trabeculae.

Osgood-Schlatter disease is characterized by tendinitis of the anterior patellar tendon.