NR 507 Patho midterm study guide completed

NR 507 Patho midterm study guide completed Mid-Term Study Guide Week 4 review concepts related to anticholinergic drugs and the treatment for asthma, bronchitis and associated pathogenesis; chronic bronchitis and related acid/base disturbances, perfusion, blood flow between the heart and lungs, asthma signs and symptoms, bronchioles, alveolar hyperinflation with asthma, polycythemia vera; mechanism of action of anticholinergic drugs to treat asthma Asthma is a chronic inflammatory disease characterized by sensitization to allergens, bronchial hyperreactivity, and reversible airway obstruction. Asthma is initiated by a type I hypersensitivity reaction primarily mediated by IgE. Airway epithelial exposure to antigen initiates both an innate and an adaptive immune response in sensitized individuals. Many cells and cellular elements contribute to the persistent inflammation of the bronchial mucosa and hyperresponsiveness of the airways, including macrophages (dendritic cells), T helper 2 (Th2) lymphocytes, B lymphocytes, mast cells, neutrophils, eosinophils, and basophils. There is both an immediate (early asthmatic response) and a late (delayed) response. In young children, airway obstruction can be more severe because of the smaller diameter of their airways. Asthma is caused by complex interaction of genetic and environmental factors. Asthma results in excess mucus production and accumulation hypertrophy of bronchial smooth muscle airflow obstruction decreased alveolar ventilation. Asthma can take two forms: extrinsic and intrinsic. The most common symptoms of both extrinsic and intrinsic asthma are: coughing, wheezing shortness of breath rapid breathing chest tightness Extrinsic: The plugs of mucus and pus from this inflammatory process can block alveolar passageways, leading to air-trapping and hyperinflation more signs and symptoms consistent with the diagnosis of asthma This process is illustrated in this image which shows the airway pathology in its entirety mast cell degranulation triggered by the excessive amounts of IGE that have airingly formed this individual that will bind that allergen as it enters the airway that mast cell degranulation releases chemicals that releases mucus production and accumulation as well as chemicals that contribute to smooth muscle constriction that smooth muscle constriction along with mucus plugs that form result in hyperinflation of the alveoli and eventual erosion of airway tissue Intrinsic: can be triggered by a variety of non-allergic factors, each causing a slightly different variation on the inflammatory process. Regardless of the underlying cause of asthma, the disease process has both a bronchoconstriction component and an inflammation component. Pharmacotherapy focuses on one or both of these components to provide fast relief for acute bronchospasms, as well as long-term control to reduce the frequency of asthma attacks. Chronic Bronchitis: pathogenesis of chronic bronchitis which begins with some sort of exposure to airborne irritants which activates bronchial smooth muscle constriction, mucus secretion, and release of inflammatory mediators (histamine, prostaglandins, leukotrienes, interleukins) from immune cells located in the lamina propria These airborne irritants can include air pollution or industrial chemicals & fumes. But the most common irritant is smoke from cigarettes and other tobacco products. Keep in mind that all of these bronchial responses are, in fact, normal responses to occasional inhalation of airborne irritants. Smooth muscle constriction is important to limit passage of the irritant deeper into the respiratory tract. Secretion of mucus and release of inflammatory chemicals are also important to help trap and defend against a potentially harmful substance. The transition from a normal, protective respiratory response to a detrimental effect occurs with …. long-term exposure to airborne irritants which promotes • smooth muscle hypertrophy à increased bronchoconstriction • hypertrophy and hyperplasia of goblet cells à mucus hypersecretion • epithelial cell metaplasia à non-ciliated squamous cells • migration of more WBCs to site à inflammation & fibrosis in bronchial wall • thickening and rigidity of bronchial basement membrane à narrowing of bronchial passageways the smooth muscle constriction, bronchial wall inflammation, and mucus plugs lead to another issue: alveolar hyperinflation. Because of the anatomical changes in the bronchioles associated with chronic irritation ventilation, especially exhalation, is compromised. Pressure differences during inhalation are high enough to force air into the alveoli. However, during exhalation the narrowing and collapse of the air passageways causes air to be trapped in the alveoli resulting in. • alveolar hyperinflation à expanded thorax • hypercapnia, (CO2 retention) and, respiratory acidosis The high concentration of CO2 creates unfavorable conditions for gas exchange, so there is • decreased O2 exchange à ventilation/perfusion (V/Q) mismatch Decreased perfusion of the pulmonary capillaries with oxygenated blood results in • chronic pulmonary hypoxia à cyanosis Poor ventilation, leading to decreased perfusion, causes Right to Left “shunting” to occur. This is the phenomenon where deoxygenated blood passes from the RV to lungs to the LV without adequate perfusion (gas exchange) Similar to other obstructive pulmonary disorders, chronic bronchitis has both a bronchoconstriction component and an inflammation component. Pharmacotherapy includes: • antitussives and expectorants – can be useful to help thin the secretions for easier expulsion and to help control coughing episodes • bronchodilators – fast- and long-acting agents are mainstays of chronic bronchitis treatment • systemic corticosteroids – particularly useful during an acute flare- up/exacerbation. • antibiotics – as needed for treatment of bacterial infections; critical to prevent any excessive immune stimulation Prophylactic immunizations (especially the pneumococcus vaccine and annual flu vaccines) are important to reduce likelihood of exacerbations triggered by respiratory infections. Clients also benefit from working with respiratory and physiotherapists to learn relatively simple physical measures that can help optimize quality of life for clients with chronic bronchitis. These physical measures include: • chest physiotherapy using postural drainage (changes in body position) and gravity to facilitate movement of mucus from the congested lower bronchial airways to the trachea for easier expulsion AND • relaxation and breathing techniques, including pursed lip breathing, similar to how you would blow a bubble, to prolong the exhalation period An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. These agents inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, and many other parts of the body. Anticholinergics are divided into three categories in accordance with their specific targets in the central and peripheral nervous system: antimuscarinic agents, ganglionic blockers, and neuromuscular blockers. Cardiovascular: GRANT FRIBERG, ERICA LUDWIG, Sheila Cardoniga review concepts related to cardiac output, cardiac contractility, preload/afterload, systole/diastole, heart valves (when they are open and closed; the production of S1 & S2), stenosis of the heart valves and effects; stroke volume, Cor Pulmonale, heart failure and physiologic processes that lead to heart failure symptoms, hypertension, calcium binding and troponin Review concepts related to cardiac output (cardiac contractility, preload, afterload): cardiac output: how much blood the heart pumps through the circulatory system in 1 minute. cardiac contractility: determined by Ca+2 availability and its interaction with actin-myosin. increased by sympathetic stimulation (e.g. fever, anxiety, ↑ thyroxine). decreased by low ATP levels (e.g. ischemia, hypoxia or acidosis). preload: volume of blood received by the heart, also the pressure of the blood on the muscle fibers in the ventricles of the heart at the end of diastole. degree of myocardial fiber length stretch before contraction. Degree of stretch is influenced by end-diastolic ventricular volume (EDV) which equals the amount of blood entering ventricle during diastole. Increased by CHF and hypervolemia. Decreased by cardiac tamponade or hypovolemia (hemorrhage, dehydration). afterload: pressure or resistance the heart has to overcome to eject blood. amount of tension each ventricle must develop during systole to open SL valves & eject blood. Influenced by ventricle wall thickness (muscle strength), Increased thickness=decreased tension. Influenced by arterial pressure (resistance to ejection), increased pressure=increased tension. Influenced by ventricle chamber size (blood volume capacity), increased chamber size=increased tension. Afterload is increased by systemic hypertension, valve disease or COPD (ex. pulmonary hypertension). Afterload is decreased by hypotension or vasodilation. Systole: diastole: heart valves (when they are open and closed; the production of S1 & S2): stroke volume: volume of blood ejected by each ventricle/systole (70 mL) and is determined by preload, contractility, and afterload. Cor Pulmonale: right heart failure. Inability of the RV to provide adequate blood flow into pulmonary circulation. Caused by pulmonary disease, RV MI, RV hypertrophy, pulmonary SLV or tricuspid valve damage, or secondary to left heart failure. High pulmonary vascular pressure increases RV contraction force (afterload). RV is unable to empty completely which results in increased RV preload. RA is unable to empty completely which results in an increased RA preload. Increased vena cava and systemic venous volume and pressure occurs. The fluid is forced out into peripheral tissues. This causes jugular distention, hepatosplenomegaly, peripheral edema and left heart failure. heart failure: cardiac dysfunction caused by inability of the heart to provide adequate cardiac output, resulting in inadequate tissue perfusion. Types of HF, left heart failure (CHF), right heart failure (cor pulmonale), and high-output failure. Left heart failure: inability of LV to provide adequate blood flow into systemic circulation. Caused by systemic hypertension, LV MI, LV hypertrophy, aortic SLV or bicuspid valve damage secondary to right heart failure. High systemic vascular pressure increases the LV contraction force which causes increased afterload. The LV is unable to eject normal amount of blood which causes an increase in LV preload. The LA is unable to eject normal amount of blood which causes an increased LA preload. This increases the blood volume and pressure in pulmonary veins and fluid is forced out into the pulmonary tissues. This all causes pulmonary edema, dyspnea, and right heart failure. Right heart failure: see Cor Pulmonale High-Output failure: inability of heart to pump sufficient amounts of blood to meet the circulatory needs of the body, despite normal blood volume and cardiac contractility. Caused by severe anemia, nutritional deficiencies, hyperthyroidism, sepsis, extreme febrile state. Cardiac output (CO): the amount of blood the heart pumps throughout the body per minute CO is calculated by multiplying HR (beats per minute) by stroke volume (liter of blood per beat) à(HR X SV=CO), Normal adult CO is approx. 5L/min Stroke volume: the volume of blood ejected per beat during systole The pumping action of the heart consists of contraction and relaxation. Each ventricular contraction and the relaxation that follows makes up the cardiac cycle. Diastole: the period of cardiac relaxation. During diastole, the blood (from the atrium) fills the ventricles. DIASTOLE=RELAXATION Systole: the period of ventricular contraction. The contraction of the ventricles forces blood out of the of the ventricles and into the pulmonary system. SYSTOLE=CONTRACTIONàThink contrACTIONàThe action in contraction is the pushing of the blood out of the heart 4 FACTORS AFFECT CARDIAC OUTPUT: Preload, afterload, contractility, and heart rate Preload: the VOLUME of blood inside the ventricle and the end of diastole (relaxation) . It is determined by the amount of venous blood returning to the ventricle during diastole (relaxation) and the amount of blood remaining in the ventricle after systole (contraction) Afterload: afterload is the RESISTANCE to ejection of blood from the left ventricle. It is the load that the heart muscle needs to move during contraction Contractility: represents the ability of the myocardial muscle to contract. It is the FORCE of heart contraction. It can’t be measured directly. Heart rate: HR is controlled by the SA node in the electrical conduction system of the heart. Many things affect HR including medications, hormones (epinephrine and norepinephrine), and neuropsychological factors (stressors, depression). cardiac output: how much blood the heart pumps through the circulatory system in 1 minute. cardiac contractility: determined by Ca+2 availability and its interaction with actin-myosin. increased by sympathetic stimulation (e.g. fever, anxiety, ↑ thyroxine). decreased by low ATP levels (e.g. ischemia, hypoxia or acidosis). preload: volume of blood received by the heart, also the pressure of the blood on the muscle fibers in the ventricles of the heart at the end of diastole. degree of myocardial fiber length stretch before contraction. Degree of stretch is influenced by end-diastolic ventricular volume (EDV) which equals the amount of blood entering ventricle during diastole. Increased by CHF and hypervolemia. Decreased by cardiac tamponade or hypovolemia (hemorrhage, dehydration). afterload: pressure or resistance the heart has to overcome to eject blood. amount of tension each ventricle must develop during systole to open SL valves & eject blood. Influenced by ventricle wall thickness (muscle strength), Increased thickness=decreased tension. Influenced by arterial pressure (resistance to ejection), increased pressure=increased tension. Influenced by ventricle chamber size (blood volume capacity), increased chamber size=increased tension. Afterload is increased by systemic hypertension, valve disease or COPD (ex. pulmonary hypertension). Afterload is decreased by hypotension or vasodilation. Systole: diastole: heart valves (when they are open and closed; the production of S1 & S2): the production of S1 and S2 Unidirectional blood flow through the heart is maintained by four valves located within the chambers of the heart: two atrioventricular (AV) valves: tricuspid & bicuspid (mitral) two semilunar valves: pulmonary & aortic The superior & inferior vena cava carry systemic DEOXYgenated blood to the right atrium. The tricuspid valve opens to allow blood flow into the right ventricle. The pulmonary semilunar valve opens to allow blood flow into the pulmonary trunk, a large blood vessel which divides to form the left and right pulmonary arteries that carry blood to the lungs and eventually into the alveolar capillaries where gas exchange will occur. The pulmonary veins return the OXYgenated blood to the left atrium. The bicuspid valve opens to allow blood flow into the left ventricle. The aortic semilunar valve opens to allow blood flow into the aorta, a large blood vessel that divides to form the brachiocephalic, left common carotid, and subclavian arteries that will further branch to carry blood to the rest of the body. The system of four valves just described, open and close in response to myocardial contraction and pressure changes within the heart. The cardiac cycle begins with ventricular diastole when the muscle cells in the ventricles are relaxed, allowing for passive movement of 70% of blood from the atria to the ventricles, driven primarily by gravitational flow. The remaining 30% of blood is “pumped” into the ventricles during atrial systole, the contraction of muscle cells located in the left and right atria. This prompts closure of the AV valves to prevent backflow of blood into the atria. The closure of the valves can be auscultated and corresponds to the first heart sound (S1). As pressure builds in the ventricles from the blood volume, this pushes the semilunar valves open. Meanwhile, the muscle cells of the ventricles contract (ventricular systole) and 55-70% of the blood is “pumped” from the ventricles into pulmonary and systemic circulation. This volume of blood is referred to as the cardiac ejection fraction. As the ventricles empty, pressure drops in the ventricles, forcing closure of the semilunar valves to prevent backflow of blood into the ventricles. The closure of these valves can also be auscultated and corresponds to the second heart sound (S2). Stenosis of the heart valves and effects: In valvular stenosis, the valve orifice is constricted and narrowed, impeding the forward flow of blood and increasing the workload of the cardiac chamber proximal to the diseased valve. Intraventricular or atrial pressure increases in the chamber to overcome resistance to flow through the valve. Increased pressure causes the myocardium to work harder, causing myocardium hypertrophy. In valvular regurgitation (also called insufficiency or incompetence) the valve leaflets, or cusps, fail to shut completely, permitting blood flow to continue even when the valve is supposed to be closed. During systole or diastole some blood leaks back into the chamber proximal to the incompetent valve, producing a murmur on auscultation. Valvular regurgitation increases the volume of the blood the heart must pump and increases the workload of the affected chamber. Increased volume leads to chamber dilation, and increased workload leads to hypertrophy. Aortic stenosis: is the most common valvular abnormality. The three common causes are 1.) calcific degeneration related to aging (aortic sclerosis), 2.) congenital bicuspid valve, 3.) inflammatory damage caused by rheumatic heart disease (RHD). Untreated aortic stenosis can lead to dysrhythmias, MI, and heart failure. The classic manifestation of aortic stenosis are angina, syncope, and heart failure Mitral Stenosis: impairs the flow of blood from the left atrium to the left ventricle. Mitral stenosis is the most common form of RHD. Continued increases in left atrial volume and pressure cause chamber dilation and hypertrophy and eventually result in pulmonary HTN. The outcomes of untreated chronic mitral stenosis are pulmonary HTN and right ventricular failure. The risk of developing atrial dysrhythmias (especially fibrillation) and dysrhythmia-induced thrombi is high. Signs and symptoms such as jugular venous distention and peripheral edema, result from pulmonary congestion and right heart failure. stroke volume: volume of blood ejected by each ventricle/systole (70 mL) and is determined by preload, contractility, and afterload. Cor Pulmonale: right heart failure. Inability of the RV to provide adequate blood flow into pulmonary circulation. Caused by pulmonary disease, RV MI, RV hypertrophy, pulmonary SLV or tricuspid valve damage, or secondary to left heart failure. High pulmonary vascular pressure increases RV contraction force (afterload). RV is unable to empty completely which results in increased RV preload. RA is unable to empty completely which results in an increased RA preload. Increased vena cava and systemic venous volume and pressure occurs. The fluid is forced out into peripheral tissues. This causes jugular distention, hepatosplenomegaly, peripheral edema and left heart failure. heart failure: cardiac dysfunction caused by inability of the heart to provide adequate cardiac output, resulting in inadequate tissue perfusion. Types of HF, left heart failure (CHF), right heart failure (cor pulmonale), and high-output failure. Left heart failure: inability of LV to provide adequate blood flow into systemic circulation. Caused by systemic hypertension, LV MI, LV hypertrophy, aortic SLV or bicuspid valve damage secondary to right heart failure. High systemic vascular pressure increases the LV contraction force which causes increased afterload. The LV is unable to eject normal amount of blood which causes an increase in LV preload. The LA is unable to eject normal amount of blood which causes an increased LA preload. This increases the blood volume and pressure in pulmonary veins and fluid is forced out into the pulmonary tissues. This all causes pulmonary edema, dyspnea, and right heart failure. Right heart failure: see Cor Pulmonale High-Output failure: inability of heart to pump sufficient amounts of blood to meet the circulatory needs of the body, despite normal blood volume and cardiac contractility. Caused by severe anemia, nutritional deficiencies, hyperthyroidism, sepsis, extreme febrile state. Heart Failure and Physiologic processes that lead to heart failure and symptoms, hypertension, calcium binding and troponin Heart Failure Pathophysiology of Ventricular Remodeling As you review this illustration, you will notice that inability of the myocardium to propel blood in a forward direction is the trigger for the symptoms seen in Congestive Heart Failure (CHF). Damage to the myocardium from an MI or ischemic heart disease could be the cause of the dysfunction, but hypertension can also create heart failure. As the pressure in the aorta increases, the heart must overcome higher and higher resistance in order to move blood forward through the circulatory system. As the heart is no longer able to contract with enough force to eject blood against the increased aortic pressure (afterload), the volume of blood ejected by the left ventricle decreases and blood begins to backflow and congest in the pulmonary system. This results in CHF. The inability of the heart to function as a pump causes a decreased cardiac output and a decreased perfusion of organs throughout the body. The kidneys are highly perfusion-dependent organs, and when cardiac output decreases, so does perfusion of the kidneys. The renin- angiotensin-aldosterone (RAA) system is activated in an attempt to increase perfusion of the kidneys. The RAA system responds when the kidney releases renin, which will trigger the liver to convert angiotensinogen into angiotensin I. Angiotensin I will travel to the lungs where it is converted by the enzyme known as angiotensin converting enzyme (ACE) into angiotensin II. Angiotensin II is a potent vasoconstrictor that causes blood vessels to constrict with resulting hypertension. Simultaneously, angiotensin II causes the adrenal cortex to secrete aldosterone, which causes the kidney tubules to reabsorb sodium and water. The increased water results in increased fluid volume in the body (preload), which also increases blood pressure. So, the RAA will increase both preload (circulatory fluid volume) and afterload (resistance to forward flow of blood in the arterial system). Both result in an increased cardiac workload and the worsening of heart failure symptoms. If the condition is not corrected, the ventricle experiences hypertrophy and ventricular dilation with further impaired contractility. Either the left or right ventricle (or both) can fail, although left ventricular dysfunction is more common. Chronic left ventricular failure results in high pressures in the pulmonary system because fluid that is not ejected into the central circulation by the left ventricle will back up through the pulmonary vein and create pulmonary congestion. Eventually, the right ventricle will experience hypertrophy as a result of contracting against increased pulmonary pressures as it attempts to move blood toward the lungs. Right heart failure secondary to left heart failure is known as Cor Pulmonale. When the right heart fails, the blood that can’t be ejected will congest in the systemic circulation and result in dependent edema. Hypertension: is consistent elevation of systemic arterial blood pressure. In 2017 HTN was redefined as a SBP 130 or greater or a DBP of 80 or greater. Pathophysiology of HTN: Numerous genetic vulnerabilities have been linked to HTN in combination with environmental risks, cause neurohumoral dysfunction (SNS, RAA system, and the natriuretic hormones) and promote inflammation and insulin resistance. Insulin resistance and neurohumoral dysfunction contribute to sustained systemic vasoconstriction and increased peripheral resistance. Inflammation contributes to renal dysfunction, which in combination with the neurohumoral alterations, results in renal salt and water retention and increased blood volume. Increased peripheral resistance and increased blood volume are two primary causes of sustained HTN. Calcium binding and troponin: Unlike skeletal and smooth muscle, cardiac muscle never rests so it requires: (1) An adequate levels of electrolytes (Na+, K+ and especially Ca+2) for muscle contraction To facilitate this, cardiac muscle cells contain a more extensive T-tubule and sarcoplasmic reticulum system than skeletal muscle cells. These features are important to allow extra calcium storage and transport within the cell. (2) Muscle cell contraction requires high levels of energy in the form of ATP Mitochondria, the primary site of cellular ATP synthesis, make up 25% of the cardiac cell volume – the highest in any type of cell. (3) The mitochondria require constant oxygen supply to maintain the aerobic metabolism processes that generate ATP. To accommodate this, cardiac tissue itself is highly vascularized to provide oxygenated blood delivery. It is estimated that there is the equivalent of 1 capillary bed per muscle cell. Furthermore, cardiac muscle cells are linked together by intercalated disks which form a latticework of channels that allow cells to function as a single unit (syncytium). So even though the heart itself is composed of hundreds of thousands of individual cells, it is essentially functioning as a single large cell – each muscle cell contracting in synchrony with its adjacent cells. Within each cardiac muscle cell, the proteins actin and myosin are arranged in contractile units called sarcomeres. Muscle contraction occurs when actin and myosin interact, a process known as the sliding filament theory. In the resting, non-contractile state another protein, troponin, holds the molecule tropomyosin in position to block myosin-binding sites on actin. Changes in intracellular ion concentrations result in electrical voltage changes which stimulate Ca+2 release from the sarcoplasmic reticulum. The positively charged calcium ion has a high affinity to bind to the negatively charged troponin. This binding causes a physical shift of the tropomyosin, allowing exposure of the expose myosin binding sites. The actin-myosin proteins can interact and the individual muscle fiber units contract. ATP is required to facilitate this interaction. From this brief description it is obvious that adequate electrolyte and ATP levels are essential for cardiac muscle contraction. Hypoxic conditions, or even small deviations in electrolyte levels, can have adverse effects on cardiac muscle cell contractility. For example, during acidotic conditions, (which can occur from build-up of lactic acid during hypoxia) the excess H+ can bind to the troponin instead of the Ca+2. The positively-charged H+ is too small to displace the troponin molecule, resulting in decreased contractility. ● Troponin, another relaxing protein, associates with the tropomyosin molecule, forming the troponin-tropomyosin complex. The troponin complex has three components TROPONIN T aids in binding of the troponin complex to actin and tropomyosin, TROPONIN I inhibits the ATPase of actomyosin, and TROPONIN C contains binding sites for the calcium ions involved in contraction. TROPONIN T and I molecules are released into the bloodstream during MI. They are measured to evaluate if an MI or other damage has occurred. Once troponin and tropomyosin cover the myosin-binding sites on actin, the cross-bridges release Ca and the myocardium relaxes. THIS IS HEMODYNAMICS! If you do not have a grasp of hemodynamics, I suggest watch this video Put hemodynamics into practice…(This may help) Pt has an MIà MI damages myocardiumà damaged myocardium leads to decreased contractility and decreased EFà decreased contractility leads to increased afterload (pulmonary hypertension that leads to pulmonary vascular resistance)à increased afterload can lead to heart failure r/t the inability of the heart to properly move blood to the pulmonary system… Hematology: JAMIE BASSETT, SARAH CLARK, BOBBI LEHMEN review concepts related to hematopoiesis, risk factors and causes for developing any type of anemia, iron-deficiency anemia, erythrocyte function and lifespan, sickle-cell anemia, thalassemia, pernicious anemia causes, hemolytic anemia, erythropoietin, functions of hemoglobin; development of anemia due to gastrectomy; effects of being transfused with incorrect blood type Hematology: I. review concepts related to hematopoiesis 1. Hematopoiesis: process involving the formation of the mature, functional red blood cells, white blood cells, platelets 2. Function is to form: a. 1. Red blood cells b. 2. White blood cells c. 3. Platelets d. 4. Dendritic cells e. 5. Osteoclasts 3. Hematopoiesis: the site of blood cell formation-varies with age a. 3rd week gestation: fetal structure, yolk sac, is the initial site b. Another month later, the fetal process shifts to the liver and spleen c. 5th month of gestation fetal skeletal structure is established and bone marrow takes over the process d. Birth-5 years, red marrow of all bones makes blood cells-keep up with oxygenation needs for the growing child e. After age 20-body growth stabilizes-it occurs in the red marrow in larger bones: ilium, vertebrae, cranium, jaw, sternum, ribs, humerus, femur i. Embryonal stage: Yolk sac ii. Fetal stage: Live and spleen iii. Birth: bone marrow iv. Young Adult: axial skeleton (90%) 4. Occurs throughout life and is stimulated by: a. Infiltration of yellow (fatty) bone marrow with red marrow cells b. Faster proliferation/differentiation of stem and daughter cells i. Hematopoietic stem cells (HSC): progenitors of all hematologic cells ii. HSCs proliferate and differentiate under control of numerous growth factors and cytokines to form 3 types of blood cells 1. RBCs, WBCs, Platelets 5. The process in the normal marrow ensures the blood is constantly replenished with blood cells 6. Lifespan of Cells: a. RBCs: 120 days b. Platelets: 7-10 days c. Neutrophils: 7 hour half-life 7. Erythropoiesis: the formation of red blood cells a. Stimulated by androgens (testosterone) i. Why males have higher hct levels 8. Erythropoietin (EPO) growth factor-made by the kidney (small amnt by liver) in response to tissue hypoxia 9. Erythrocyte function and lifespan a. Normal RBC level – 4.2-6.2 million/mm3 b. Makes up about 45% of our blood volume c. We replenish 1% of circulating RBC mass every 24 hours = 2.5 million RBC/second; but can go up to 17 million RBC/sec if hypoxic!! d. The growth factor erythropoietin binds to the hemocytoblast and triggers a series of genetic and enzymatic changes within the progenitor cell, setting it on the course to develop into mature erythrocyte. e. Similar to how a sculptor might mold a ball of clay, the proerythroblast morphs into an erythroblast, a normoblast, a reticulocyte (essentially a “teenage” RBC) that is released from the bone marrow into circulation, where, in 1-2 days, it will develop into the mature erythrocyte. f. It normally is a 7-day process to “build” a RBC. g. The mature RBC structure is described as a biconcave, spherical disk; this structure allowing maximum surface area for gas exchange (the primary role of RBCs) and also reversible deformability to squeeze thru capillaries (the primary site where gas exchange occurs). h. The mature RBC lacks a nucleus, ribosomes, and mitochondria. Without these structures, RBCs cannot divide or do protein synthesis, and can only perform anaerobic metabolism = decreased ATP synthesis. i. The inability to generate new proteins and produce larger amounts of ATP severely limits the ability of a RBC to sustain itself for very long. Therefore, the lifespan of an erythrocyte or mature RBC in circulation is approximately 100-120 days - but in that time frame it will have traveled thousands of miles through our vascular system! j. RBCs are essentially a sack of hemoglobin! k. Functions of Hemoglobin l. Estimated approximately 300 million Hb molecules/RBC = 90% of the dry weight of the cell. m. males: 16 g Hb/dL blood; females: 14 g Hb/dL blood n. Hemoglobin chemical composition: i. Polypeptide chains, heme molecules, iron 1. Polypeptide chain: amino acid composition varies during our lifetime. The various chains are designated as alpha, beta, gamma, delta, epsilon, and zeta ii. Adult Hgb composed of 2 alpha and 2 beta chains: synthesized by ribosomes during the early stages of RBS formation, chains wrap around the heme molecule iii. Porphyrin ring structure: heme molecule: formed in the mitochondria of the RBC iv. RBCs are not able to synthesize any additional Hgb once it loses its mitochondria and moves out of the bone marrow 1. if a RBC “only” has 290 million Hb molecules by the time it loses its mitochondria, sorry …. but that is all the Hb it will contain! v. There are 4 heme group per Hgb molecule. vi. Iron (ferrous Fe+2) binds with each heme vii. Vitamins B12 and folic acid are required for Hgb and RBC synthesis viii. O2 diffuses into the blood cells and binds to the iron in each heme molecule (oxyhemoglobin) 1. This reaction causes the Fe in the Hgb molecule to change color and gives systemic arterial blood the red color ix. Nitric Oxide (NO)-produced by endothelial cells in blood vessels-diffuses into RBCs and binds to the Hgb molecule structure 1. Beneficial because NO is released from the RBCs in minute quantities during circulation and promotes vasodilation as blood cells circulate through our capillary beds x. CO2 diffuses from tissue cells into the capillary beds and into the RBCs where it binds to Hgb (deoxyhemoglobin) 1. Reaction causes Fe in the Hgb molecule to change color again and give systemic venous blood the purple/blue color 2. CO2 will eventually be released as venous blood circulates in the pulmonary capillary beds o. Hgb plays an essential role in tissue oxygenation so it is critical that RBCs have all the necessary components to build the millions of Hb molecules in each and every RBC. 10. RBC acquire necessary components: inability to do so plays a role in some types of anemia a. Every Hgb molecule contains 4 iron atoms-iron is a very important nutrient b. Primary diet sources for iron: meats (especially red), dried beans, eggs c. Irons is absorbed through GI tract & combines with plasma protein transferrin (an iron transporter) which helps carry the iron through the bloodstream to the liver for storage as a complex ferritin i. When needed, iron is released from the liver and once again carried by transferrin through the bloodstream from the liver to the bone marrow d. Fe enters the erythroblast, the developmental stage at which Hgb synthesis occurs, and transported directly into the mitochondria. i. Only ferrous form is effective in binding to O2 e. oxidized ferric Fe+3 cannot bind O2. i. To assist with this, Vitamin C (an antioxidant) must also be present to keep Fe in +2 form. (As a clinical note, this is why iron supplements also usually contain Vitamin C!) f. Recommended iron levels vary depending on gender and age. Females age 19-50 need 18 mg Fe/day; g. females 50 and males (19) need 8 mg Fe/day. 11. Vitamin B12 (cyanocobalamin) is another important “ingredient” for the synthesis of RBCs. a. Primary dietary sources are meat, fish, poultry, dairy, making this one of the few vitamins that cannot be obtained from fruit or vegetables – which can be a concern for individuals following very strict vegan diets. b. Vitamin B12 is required for DNA, RNA, and myelin synthesis. i. RNA synthesis occurs in its absence, but abnormally large cells form. c. Because of the complexity of the chemical structure of this vitamin, it is not readily absorbed through the GI tract. Therefore, cells of the stomach secrete intrinsic factor (IF) protein to facilitate absorption of B12 from the ileum. d. Any excess B12 is stored in the liver; typically, we have a 1000-fold excess reserve so it can take years to deplete our stores of this vitamin. e. The vitamin folic acid (folate) is required for DNA and RNA synthesis (and also important for neural development in utero). f. Primary dietary sources include liver, grains and green vegetables. Direct folic acid supplementation is also important during pregnancy to help prevent neural tube defects in the developing fetus. g. Folic acid is absorbed directly from the GI tract and any excess is stored in the liver. h. Because of the large volume of RBCs formed every minute, requiring lots of DNA and RNA, reserves of this vitamin can be depleted within 2-3 months. i. RBCs have a relatively short lifespan of 100-120 days. i. This is due in part to the tremendous amount of “mileage” they put on continually circulating through our vasculature and, also to their altered metabolic capabilities that produce limited amounts of ATP. This creates electrolyte imbalances, changes in cell membrane fluidity, and overall, fragile cells. i. As blood circulates into the spleen, narrow splenic capillaries literally capture and fragment "old" RBC. j. And then because of the “wealth” of valuable chemicals that compose the 300 million Hb molecules in each RBC, macrophages in the spleen digest RBC and recycle these chemicals: amino acids from polypeptide chains are reused; heme is converted to bilirubin and stored in the liver or used for bile formation, ultimately excreted in the urine and feces; iron is bound by transferrin and transported for storage in the spleen or liver k. Note, that in the case of an asplenic individual, RBC recycling still occurs, but this process is taken over, somewhat less efficiently, by the liver. II. Risk factors and causes for developing any type of anemia 1. Anemia is a hematological disorder characterized by a reduction in the total # of circulating RBCs and/or a decrease in Hgb content or function 2. Caused by: impaired RBC production, excessive blood loss, increased RBC destruction, or any combination 3. Results in: reduced RBC # and/or Hgb level leading to decreased tissue oxygenation with S/Sx: hypoxia, dyspnea, pallor, dizziness, fatigue 4. Reduction in RBC level will be decreased blood volume-activating the renin-angiotension- aldosterone (RAA) system: which promote fluid retention and movement of interstitial fluid into the capillaries a. This will not only increase plasma volume, but also dilute the plasma further. b. The dilute blood flows faster, creating a hyperdynamic state, which “stresses” the cardiac system. c. This can progress to tachycardia and even heart failure. 5. Anemia types are classified by: a. size - normocytic, microcytic, macrocytic b. color - normochromic, hypochromic, hyperchromic (due to Hb level) c. variability - anisocytosis (variability in size), poikilocytosis (shape) 6. Hemolytic anemia: literally the “lysis” of blood cells, a. is caused by: i. infection (including parasitic and helminthic organisms, and certain hemolytic toxin-producing strains of the bacterium Escherichia coli that is found as a common cause of food poisoning outbreaks) ii. transfusion reaction (from an incorrect/incompatible blood product) iii. hemolytic disease of the newborn (Rh incompatibility issue occurring in Rh- mothers and their Rh+ fetus) iv. autoimmune reactions (either congenital or idiopathic in nature) v. drug-induced 1. Drugs are chemicals and they autoxidize (self-destruct, especially over time and/or with exposure to heat, moisture) to form H2O2(hydrogen peroxide, a free radical) which causes Fe +2 to oxidize to form Fe +3; and as mentioned earlier, this form of iron cannot can't bind O2 as well. 2. Plus, hydrogen peroxide can also attack and oxidize cell membranes to weaken them. 3. circulating blood contains Vitamin C and RBCs contain glutathione, both of which are natural antioxidants to help protect cells! b. In any of the above situations there is a premature destruction/lysis of RBCs due to enzymes or toxins produced by the infectious agent, chemical release mediated by own immune system, or due to the effects of certain chemicals/drugs. 7. Macrocytic-Normochromic Anemia: unusually large cells, but normal Hgb level a. The problem behind this is not enough building blocks (vitamins folic acid or B12) to make DNA, so erythroblasts continue to enlarge instead of undergoing cell division. This is also sometimes referred to as “megaloblastic” (mega/large) cell anemia. b. Examples include pernicious anemia and folate deficiency anemia. 8. Pernicious anemia can be caused by an autoimmune reaction. a. Almost 90% of individuals with pernicious anemia (PA) have serum Ab against GI tissue, either as a genetically-induced autoimmune condition (especially prevalent in individuals of English, Irish or Scandinavian ancestry) or an autoimmune condition acquired secondary to GI infections, particularly infections by Helicobacter pylori, the bacterium associated with development of stomach ulcers. b. PA can also develop as the result of gastritis (GI inflammatory conditions) or gastrectomy procedures that result in the loss of GI cells producing intrinsic factor, the protein necessary for Vitamin B12 absorption. The increase in bariatric procedures for weight control has contributed to an increase in the development of PA. c. The pathophysiology is straight forward: malabsorption of B12 due to lowered intrinsic factor (IF) production/secretion in the GI tract. Inadequate B12 levels result in not only decreased DNA synthesis and a reduction in RBC number, but also a decrease in nerve cell myelination, which contributes to the neuropathies also associated with pernicious anemia. d. Unfortunately, without adequate intrinsic factor to help with GI absorption, this type of anemia is not easily remedied by simple oral B12 supplementation. Very high levels of oral B12 must be ingested to force any direct GI absorption. Injections of B12 or intranasal formulations are much more effective ways to get the vitamin directly into the bloodstream. 9. Folate deficiency anemia is caused by malnutrition, alcoholism, and interactions with numerous anticonvulsant medications. a. Insufficient folate intake or ↓absorption from diet due to GI problems (often precipitated by alcohol abuse) leads to abnormal RBC formation and premature death of RBCs. b. It is estimated that 10% of Americans are folate-limited due to poor diets – so eat your veggies and folate-fortified grains! c. And as mentioned previously, there are also risks for in utero complications (neural tube defects) in folate-deficient women. 10. Microcytic-Hypochromic Anemia is characterized by small cells and low Hgb level. The most common problem contributing to this is insufficient iron availability. a. Iron deficiency anemia (IDA) is the most common type of anemia, affecting almost 20% of the world population i. Cause of IDA include: 1. inadequate dietary intake 2. chronic and or occult bleeding a. hemorrhage, colitis, cirrhosis, GI ulcers, esophageal lesions, or menorrhagia b. (Note that it only takes 2-4 mL (about 1 tsp) of blood loss per day to lose 1-2 mg iron) 3. Other less common causes of IDA include decreased ability to utilize Fe for heme synthesis a. transferrin deficiencies, mitochondrial defects 4. The pathophysiology of IDA is very simple: insufficient Fe levels or inability for mitochondria to utilize Fe effectively leads to decreased Hb synthesis and the formation of smaller, paler cells. 11. Inherited Disorders of Erythrocytes: Hemoglobinopathies a. Four genes involved in encoding synthesis of the alpha protein chains for Hb. These genes are located on chromosome #16. b. There are two genes involved in encoding synthesis of the beta protein chains for Hgb. These genes are located on chromosome #11. c. From these six different genetic loci over 300 different Hb gene defects have been documented. d. The two most common examples include sickle-cell anemia and thalassemia. 12. Sickle-cell anemia is an inherited autosomal recessive genetic disorder. As discussed in the Basics of Human Genetics presentation autosomal recessive disorders develop as the result of inheriting two abnormal genes, one from each parent. a. In the event that the individual inherits a normal Hb gene from one parent and an abnormal Hb gene from the other parent, that individual would have “sickle cell trait” and be an asymptomatic carrier. They could pass on the abnormal gene to their offspring, but they themselves would experience minimal, if any signs and symptoms of the condition. b. The pathophysiology of sickle cell anemia involves a single amino acid change on the beta- chain (the amino acid valine replaces glutamic acid). This simple change results in the formation of elongated, “sickled” Hb molecules (designated HbS) which does not bind oxygen as readily. c. Oxidative stress (such as occurs with hypoxia), anxiety, fever, cold, and dehydration further decrease oxygen binding to Hb and increases sickling tendencies of the Hb. d. The sickling of millions of hemoglobin molecules causes distortion of RBCs that house those molecules; this weakens the RBCs and they rupture after only 10-15 d in circulation. This is a type of hemolytic anemia and presents with the classic anemia S/S in addition to other serious complications. The lysis of large amounts of RBCs put the individuals at risk for circulatory iron-overload e. The abnormal RBCs also occlude cerebral, splenic and glomerular blood vessels and create a high risk for CVA, splenic and kidney damage. Damage to the spleen is especially prevalent, so many sickle-cell individuals are asplenic by adulthood. 13. The thalassemia(s) are a group of related inherited autosomal recessive genetic disorders. Similar to sickle cell anemia, the affected individual must inherit an abnormal Hb gene from both parents. a. However, unlike sickle cell anemia, thalassemia is characterized by many different possible genetic mutations. These mutations cause single or multiple amino acid changes on alpha- and/or beta-chains resulting in synthesis of Hb with abnormal chains, or even missing alpha and beta chains. Depending on the mutation, there can be varying degrees of distortion and dysfunction of the RBC. Because of the number of different possible genetic mutations, thalassemia can present in a variety of forms from minor to major and be asymptomatic in the mildest/minor forms and lethal in the most severe/major forms, such as Colley’s thalassemia. 14. Collectively, sickle cell anemia and the different forms of thalassemia represent the most common genetically inherited disorders. It is estimated that over 300 million people worldwide have one of these conditions and many millions more are carriers of these genetic traits. Furthermore, these conditions are more prevalent in individuals from certain geographic regions. Specifically, genetic mutations for these conditions are found in people of African, Mediterranean, and Southeast Asian descent. The name “thalassemia” literally translates from “thalassa” – the Greek word for sea. What would be the reason that the genetic mutations for these hemoglobinopathies persisted in the human gene pool through the centuries …. unless there was some advantage? 15. It turns out that cells that contain abnormal types of hemoglobin are more resistant to infection by the parasite that causes malaria – a disease that happens to be endemic in the same parts of the world where these types of anemia are also prevalent. Not only are the abnormal RBCs more resistant to infection, but their shortened lifespan in circulation, is not long enough to allow the malaria parasite to complete its reproduction cycle. 16. This allowed our ancestors who carried these genetic mutations, to be resistant to the deadly consequences of a malarial infection and survive long enough to have children to whom they could pass on this trait, and most importantly, continue the circle of life. Effects of being transfused with incorrect blood type 1. Haemolytic transfusion reactions • This can be immediate or delayed, with more serious reactions being caused by transfusion of ABO-incompatible red cells that bind on to the patient's anti-A/anti-B antibodies and activate the complement system. • This leads to intravascular haemolysis (destruction of the transfused red cells) and releases inflammatory cytokines that can lead to renal failure, shock and disseminated intravascular coagulation [DIC] (blood is unable to clot properly) • In the delayed reaction, pre-transfusion levels of antibodies that were too low to be detected in a cross-match means that a patient may be re-immunised with incompatible red cells which leads to a delayed transfusion with increased clearance of red blood cells. • Acute presentation: chills, fever, hypotension, hemoglobinuria, renal failure, back pain, DIC • Delayed presentation: anaemia (due to a falling Hb count, jaundice (rapid or mild) Management of patients with haemolytic transfusion reactions • Main thing is to maintain blood pressure and renal perfusion • Given IV dextran, plasma/saline and often furosemide • To alleviate shock: hydrocortisone 100mg IV, antihistamines (if severe shock give nebulised adrenaline) • Severely affected patients: give further compatible transfusion • Acute renal failure: use dialysis if necessary HEME · Hematopoiesis – blood cell formation that occurs throughout life - Site of hematopoiesis varies with age: § Initial site = fetus – begins at 3rd week of gestation, shifts to fetal liver & spleen by week 8 and to bone marrow at 5 months gestation § Birth to 5 years - red marrow of ALL bones make blood cells § After 20 years – red marrow primarily in ilium, vertebrae, cranium & jaw, sternum & ribs, humerus & femur - Stimulated by: § infiltration of yellow (fatty) bone marrow with red marrow cells § faster proliferation/differentiation of stem and daughter cells - Erythropoiesis = formation of red blood cells, stimulated by androgens (testosterone ► this is why males have a higher Hct) - Erythropoietin (EPO) = growth factor made by the kidney and liver in response to tissue hypoxia § Normal RBC level = 4.2-6.2 million/mm (approx.. 45% of blood volume) -Our body replenishes 1% of circulating RBC mass every 24 hrs (2.5 million RBC/sec), can go to 17 million RBC/sec if hypoxic! - Takes 7 days to make a RBC · Mature RBC = bioconcave, spherical disks composed of polypeptide chains, heme molecules, and iron; able to squeeze through capillaries primary site of gas exchange § RBC lacks a nucleus, ribosomes, and mitochondria = can’t divide or synthesize protein o Lifespan in circulation = 100-120 days o Carry hemoglobin (300 million Hgb molecules per RBC!) o Normal Hgb levels: Males – 16g Hgb/dL , Females – 14 g Hgb/dL - Adult Hgb = 2 alpha + 2 beta polypeptide chains ▼ Wrap around heme molecule § Heme molecule = porphyrin ring structure formed in RBC mitochondria -4 heme groups per Hgb molecule § Iron (Fe+) binds with each heme § Vitamins B12 and folic acid are required for Hgb and RBC synthesis - O2 binds to Fe+ in each heme molecule = oxyhemoglobin o Chemical reaction causes blood to change color, turning from blue to red - Nitric oxide (NO) is produced by endothelial cells in blood vessels o Diffuses into RBCs and binds to Hgb molecules o Promotes vasodilation during circulation as RBCs release O2 - CO2 binds to Hgb = deoxyhemoglobin o Released in the lungs; changes back to blue color · Iron (Fe+) § Primary diet sources = meat, dried beans, eggs § Absorbed through GI tract ►combines with transferrin ►transported to liver for storage as ferritin § Released from liver via transferrin ►bone marrow § Enters erythroblast and transported directly into mitochondria - Only ferrous iron (Fe+²) can bind to O2 - Oxidized iron (Fe+³ ) cannot bind to O2 - Need Vitamin C to keep iron in Fe+² form Iron supplements *Females 19-50 years old need 18mg/day *Females 50 and males 19 need 8mg/day · Vitamin B12 (cyanocobalamin) – primary diet sources = meat, fish, poultry, dairy (not available in fruit and veggies) § Required for DNA, RNA, and myelin synthesis § Absorbed from ileum – stomach cells secrete intrinsic factor (IR) protein to facilitate absorption § Excess B12 is stored in liver (takes years to deplete) · Folic acid (folate) – primary diet sources = liver, grains, and green vegetables § Required for DNA and RNA synthesis § Important in pregnancy to prevent neural tube defects § Excess folate stored in liver (can be depleted in 2-3 months) Recycling of RBCs · Normal recycling of RBCs occurs as metabolic processes decrease Less ATP formed ►electrolyte imbalances►decreased membrane fluidity►fragile cells · Splenic capillaries grab and filter old RBCs as they circulate in blood · Splenic macrophages digets RBCs - Recycle amino acids from polypeptide chains - Heme converted to bilirubin and stored in liver or used for bile; excess excreted in urine & feces - Iron bound by transferrin and stored in spleen or liver * In an asplenic person, this process still occurs but is taken over by the liver (less efficient) Anemia = reduction in total # of circulating RBCs and/or decrease in Hgb content or function. Risk Factors: - Diet low in iron, vitamin B-12 and folate - GI disorders - Crohns, celiac (affects the absorption of nutrients in small intestine) - Heavy periods (menstruation) - Pregnant women who don’t take a multivitamin with folic acid - Chronic conditions (i.e. cancer, kidney failure) or chronic blood loss (i.e. ulcer) - Family Hx of inherited anemia (i.e. sickle cell) - Age 65 - A history of certain infections, blood diseases and autoimmune disorders, alcoholism, exposure to toxic chemicals, and the use of some medications can affect red blood cell production and lead to anemia · Causes of Anemia: o Impaired RBC production o Excessive blood loss Or any combination of these! o Increased RBC destruction · Results in: o Reduced RBC # and/or Hgb level = decreased oxygenation S/S = hypoxia, dyspnea, pallor, dizziness, fatigue o Reduced RBC # = decreased blood volume - Activation of RAAS system - promotes fluid retention & movement of interstitial fluid into capillaries ► increases plasma volume and dilutes plasma ► blood flows faster ► hyperdynamic state ► stresses cardiac system = tachycardia, heart failure Classifications of Anemia · Size = normocytic, microcytic, macrocytic · Color = normochromic, hypochromic, hyperchromic (due to Hgb level) · Variability + anisocytosis (size), poikilocytosis (shape) Normocytic-Normochromic Anemia = normal cell size & Hgb level BUT low cell # Examples: post-hemorrhagic anemia, aplastic anemia, hemolytic anemia Post-hemorrhagic anemia = acute blood loss from severe trauma, surgery, or L&D complications - A normal, healthy young adult can lose between 500-1000 mL (10-20% of total blood volume) with minimal effects - Compensation & recovery begins within 24 hours for losses 1500 mL Aplastic anemia – caused by (“agent”) o Chemical or radiation exposure (side effect of cancer treatment) o Viral-induced (i.e. hepatitis, EBV, CMV) o Tumors (i.e. multiple myeloma) o Abx and other Rx (PCN, chloramphenicol, phenytoin, diuretics, antidiabetics, sulfa drugs) o Congenital defects (Fanconi’s anemia = rare - 1 in 500,000) - Pathophysiology: “Agent” destroys red bone marrow and is replaced by yellow “fatty” marrow – doesn’t produce blood cells -Leads to pancytopenia = decrease in all types of blood cells Effects of bone marrow suppression = 1) s/s of anemia r/t loss of oxygenation capability (no RBCs) 2) Problems w/ clotting (no platelets) 3) Increase in infections (no WBCs) Hemolytic anemia – caused by: certain hemolytic toxin-producing strains of E.coli o Infection parasitic & helminthic organisms o Transfusion reaction o Hemolytic disease in newborn (Rh incompatibility) o Autoimmune reaction (congenital or idiopathic) o Drug-induced - Pathophysiology: Premature destruction or RBCs due to enzymes/toxins that are produced by infectious agent, mediated by own immune system, or effects of chemicals/drugs · risk factors and causes for developing any type of anemia, iron-deficiency anemia, erythrocyte function and lifespan Macrocytic-Normochromic Anemia = unusually large cells, but normal Hgb level - Deficiency in folic acid or B12 – not enough building blocks to make DNA ►erythroblasts continue to enlarge instead of dividing (meganloblastic) Examples: pernicious anemia (PA), Iron-deficiency anemia Iron-deficiency anemia – caused by: - Malnutrition - Alcoholism - Anticonvulsant Rx Pathophysiology: o Insufficient folic acid (folate) or decreased absorption from diet due to GI problems § Abnormal RBC formation § Premature death of RBCs *Not enough folic acid during pregnancy = increased risk for neural tube defects review concepts related to hematopoiesis, risk factors and causes for developing any type of anemia, iron-deficiency anemia, erythrocyte function and lifespan, sickle-cell anemia, thalassemia, pernicious anemia causes, hemolytic anemia, erythropoietin, functions of hemoglobin; development of anemia due to gastrectomy; effects of being transfused with incorrect blood type Genitourinary/Renal: SARAH THOMPSON, CLAUDIA EVERS, ASHLEY WILLIAMS, KYNA APONTE Anatomy and physiology of the kidney (McCance, pg 1229): - Each kidney weighs approximately 5 ounces. Right kidney is slightly lower and displaced towards the liver. - Renal Capsule: tightly adhering that surrounds each kidney and the kidney is then embedded in a mass of fat. - Renal Fascia: double layer of fibrous tissue that attaches each kidney to the posterior abdominal wall. - Hilum: a medial indentation in the kidney and is the location of the entry and exit for the renal blood vessels, nerves, lymphatic vessels, and ureter. - Cortex: outer layer of the kidney and contains all of the glomeruli, most of the proximal tubules, and some segments of the distal tubule. - The renal cortex and pyramids compose the parenchyma or functional portion of the kidney. Within the parenchyma are specialized microscopic anatomical structures called nephrons (wk 4 lesson). - Medulla: forms the inner part of the kidney. Consists of regions called the pyramids. - Renal columns: an extension of the cortex and lie between the pyramids and extend to the renal pelvis. - The apexes of the pyramids project into minor calyces (cup-shaped cavities) that unite to form major calyces. - Minor Calyces: receive urine from the collecting ducts through the renal papilla. - The major calyces join to form the renal pelvis, which connects with the proximal end of the ureter. - The walls of the calyces, pelvis, and ureter are lined with epithelial cells and contain smooth muscle cells that contract to move urine to the bladder. - The structural unit of the kidney is the lobe, composed of a pyramid and the overlying cortex. There are 14 lobes in each kidney. - Nephron: - The nephron is the functional unit of the kidney and works as an ultrafiltration unit for filtrate from the glomerulus. - At birth, each kidney contains approximately 1 million nephrons. But when a nephron ages or is irreversibly damaged, the body is not able to replace it. By age 80, approximately 40% of nephrons are nonfunctional. - The nephron is a multicellular structure consisting of: - Bowman’s capsule (sometimes referred to as the glomerular capsule) and a tubule system divided in the proximal convoluted tubule (PCT), Loop of Henle, distal convoluted tubule (DCT) and a collecting duct. - Four processes occur in the nephron during the formation of urine: - Filtration, reabsorption, secretion, excretion. - 1. Filters plasma at glomerulus. - 2. Reabsorbs and secretes different substances along tubular structures. - 3. Forms a filtrate of protein-free fluid (ultrafiltration). - 4. Regulates the filtrate to maintain body fluid volume, electrolyte composition, and pH within narrow limits. - Damage to the nephron: We do not make new ones after they are lost. This is why the kidney functions less as we age. Glomerular Filtration: - Glomerular filtration is the movement of fluid and solutes across the glomerular capillary membrane into the Bowman space. - Blood pressure forces water and disolves plasma components such as (glucose, ions, amino acids, urea, and creatinine= “the filtrate”) through the glomerulus & Bowman’s capsule into the renal tubule system. Tubular reabsorption: - The movement of fluids and solutes from the tubular lumen to the peritubular capillary plasma. - Selective return of water and solutes such as (glucose, ions, amino acids, urea = “the filtrate”) FROM the filtrate of the nephron tubule system INTO the bloodstream of the peritubular capillaries (*capillaries surround the tubular area of each nephron*). - 65% of salt and water and most organic substances are reabsorbed in the Proximal Convoluted Tubule (PCT) - Remainder of water and ions are reabsorbed throughout tubule system; ADH & aldosterone influence these amounts. Tubular secretion: - The transfer of substances from the plasma of the peritubular capillary to the tubular lumen. - Movement of material (urea, NH, H+, K+, misc chem. Medications, additives, food coloring etc…) FROM the bloodstream of the peritubular capillaries INTO the filtrate of the nephron tubule system. → Urinary excretion: final elimination of wastes (Urine). Conditions associated with renal failure: - Hypertension, diabetes mellitus, systemic lupus erythematosus or intrinsic kidney disease including kidney stones, acute kidney injury, chronic glomerulonephritis, chronic pyelonephritis, obstructive uropathies or vascular disorders. - Diabetes is the most common cause of renal failure or end stage renal disease. High blood pressure is the second most common cause. Other problems that can cause kidney failure include autoimmune diseases, such as lupus and IgA nephropathy, Genetic diseases such as polycystic kidney disease, nephrotic syndrome, urinary tract problems. - Calculi blockage of ureter: Renal Calculi ·Cause = renal calculi is unknown ·Risk factors: ·Men ·Secrete high concentrations of calcium, magnesium, ammonium, phosphate, uric acid, or cystine in the urine ·pH of the urine can also increase the likelihood of stone formation O Low pH increasing the risk of uric acid stones O High pH increasing the risk of calcium phosphate stones ·Calcium stones account for 70% to 80% of all renal calculi ·Precipitates and stones less than 5 millimeters are often passed through the urinary tract ·Larger stones may not be able to pass or may create a partial or complete urinary tract obstruction with subsequent flank pain, nausea, and vomiting. ·If stones are 1 centimeter or larger, they have little to no probability of passing spontaneously. ·The APN may prescribe pain medications to relieve discomfort caused by renal calculi Benign prostatic hypertrophy: Benign prostatic hypertrophy The enlargement of the prostate gland. This condition becomes a problem when prostatic tissue compresses the urethra, where it passes through the prostate resulting in frequency of lower urinary tract symptoms. The prevalence among U.S men 60 years and older is about 50% and among me 70 years or older is 90%. This is common and involves a complex pathophysiology with several endocrine and local factors and remodeled microenvironment. Its relationship to aging is well documented. Begins around 40-45 years of age slowly until death. Although dihydrotestosterone (DHT) is necessary for normal prostatic development, its role in BPH remains unclear. Current causative theories focus on levels and rations of endocrine factors such as androge