PATH370 MIDTERM STUDY GUIDE WEEKS 1-2 CHAPTER 1: INTRODUCTION TO PATHOPHYSIOLOGY AND PATHOPHYSIOLOGY TERMINOLOGY Know all vocabulary and definitions from this chapter Acute: short-lived; may have severe manifestation Chronic- may last months to years, sometimes following an acute course Clinical manifestations- symptoms, signs, syndrome, latent period, prodromal period, subclinical stage, acute clinical course, chronic clinical course, exacerbation, remission, convalescence, sequelae Diagnosis- the designation as to the nature or cause of a health problem Endemic- native to a local region Epidemic- spread to many people at the same time Epidemiology- study of the patterns of disease involving populations Etiology- study of causes/reasons for phenomena Exacerbation- increase in severity, signs, or symptoms Iatrogenic- cause results from unintended or unwanted medical treatment Idiopathic- cause is unknown Incidence- reflects the number of new cases arising in a population at risk during a specified time Incubation period- the phase during which the pathogen begins active replication without producing recognizable symptoms in the host. The duration is influence by additional factors, including the general health of the host, the portal of entry, and the infectious dose Insidious- coming on gradually and subtle development Latent period- time between exposure of tissue to injurious agent and first appearance of signs and/or symptoms Morbidity- describes the effects an illness has on a person’s life. Not only concerned with the occurrence or incidence, but with persistence and the long term consequences Mortality- death rates for a specific population. Also described in terms of the leading causes of death according to age, sex, race, and ethnicity Multifactorial- multiple alleles at different loci affect the outcome Occurrence- frequency of a disease without defining incidence or prevalence Pandemic- spread to large geographic areas Pathogenesis- development or evolution of disease, from initial stimulus to ultimate expression of manifestations of disease Pathology- focuses on the changes in body tissues and organs that cause or are caused by disease Pathophysiology- the functional changes associated with or resulting from disease or injury Physiology- the science of the functioning of the living organism and its parts and processes Prevalence- the number of cases of a specific disease present in a given population at a certain time Prodromal period- time during which first signs and/or symptoms appear or onset of disease occurs Prognosis- the probable outcome and prospect of recovery from a disease Remission- decrease in severity, signs, or symptoms; may indicate disease is cured Risk factor- a factor that when present increases the likelihood of disease Sensitivity- probability that a test will be positive when applied to a person with a particular condition Sequelae- subsequent pathologic condition resulting from an acute illness Signs- objective or observed manifestation of disease Specificity- probability that a test will be negative when applied to a person without a particular condition Subclinical stage- patient functions normally; disease processes are well established Symptoms- subjective feeling of abnormality in the body Syndrome- a set of signs and symptoms not yet determined to delineate a disease CHAPTER 2: HOMEOSTASIS AND ADAPTIVE RESPONSES TO STRESSORS - 3 stages of Selye’s General Adaptation Syndrome Alarm reaction: fight-or-flight response due to stressful stimulus. It provides a surge of energy and physical alterations to either evade or confront danger. +allostatic state: refers to the activity of various systems in attempting to restore homeostasis Stage of resistance: the activity of the nervous and endocrine systems in returning the body to homeostasis. To survive the body must move past alarm and into this supportive stage of the allostatic return of homeostasis. As the body moves into the stage of resistance, the SNS and the adrenal medulla and cortex are functioning at full force to mobilize resources to manage stressors. Stage of exhaustion: point where body can no longer return to homeostasis. +Selye’s postulated that when energy resources are completely depleted, death occurs bc the organism is no longer able to adapt. +Allostatic overload: cost of body’s organs and tissues for an excessive or ineffectively regulated allostatic response - role of hypothalamus and function of corticotropin releasing hormone Hypothalamus: responsible for the production of many of the body’s essential hormones, chemical substances that help control different cells and organs. The hormones released are for temperature regulation, thirst, hunger, sleep, mood, sex drive, and the release of other hormones within the body. (catecholamines, norepinephrine & epinephrine released here) Corticotropin releasing hormone: (CRH) stimulates the release of corticotropin by the anterior pituitary gland. Normally released by the mother and embryo soon after embryo implants the uterus. Protects it from immunologic rejection by the mother (miscarriage) - role of anterior pituitary and function of adrenocorticotropic hormone (ACTH) Anterior pituitary: regulates stress, growth, reproduction, and lactation. Its regulatory functions are achieved through the secretion of peptide hormones that act on target organs including adrenal gland, liver, bone, thyroid gland, and gonads Adrenocorticotropic hormone: (ACTH) stimulates the production and release of cortisol from the cortex to the adrenal gland. CRH from the hypothalamus acts on the pituitary which secretes ACTH - role of posterior pituitary and function of antidiuretic hormone/vasopressin (ADH) Posterior pituitary: stores and secretes oxytocin and antidiuretic hormone Antidiuretic hormone: (ADH) acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood and to constrict blood vessels - Role of adrenal glands and functions of: ( catecholamines- epinephrine/norepinephrine, corticosteroids- cortisol/aldosterone) adrenal glands: produce hormones that help the body control blood sugar, burn protein and fat, react to stressors, and regulate blood pressure (cortisol and aldosterone) Catecholamines: enable the body to rapidly take action to fight or flee the stressor; through the sympathetic adrenal medullary system. Which releases norepinephrine and epinephrine. Catecholamines: ● Aide in elevation of cardiac output ● Vasomotor (constriction of blood vessels) changes ● Lipolysis (breakdown of fats and other lipids) ● Glycogenolysis ● Insulin suppression ● Increased respiration ● Enhanced blood coagulation Corticosteroids: they have regulatory roles in the cardiovascular system and in maintaining fluid volume, and contribute to metabolism, immunity, and inflammatory responses, brain function, and even reproduction. They are lipid-soluble hormones. ● Primary is cortisol/ aldosterone: secreted by the adrenal cortex in response to ACTH from the anterior pituitary; which is in turn affected by the release of CRH. ○ Gluconeogenisis ○ Protein catabolism ○ Inhibition of glucose uptake ○ Suppression of protein synthesis ○ Stabilization of vascular reactivity ○ Immune response suppression ( cortisol is the primary glucocorticoid. Aldosterone is the primary mineral corticoid.) - functions of endorphins/enkephalins and Immune Cytokines endorphins and enkephalins: endogenous opioids (body’s natural pain relievers) +raise pain threshold; produce sedation and euphoria Cytokines are a group of proteins secreted by the immune system that act as chemical messengers. Cytokines released from one cell affect the actions of other cells by binding to receptors on their surface. You can think of these receptors as mailboxes. They receive the cytokine's chemical message, and then the receiving cell performs activities based on that message. - Physical, behavioral, and emotional indicators of stress Physical indicators: low energy, headaches, upset stomach, aches, insomnia, frequent colds Behavioral indicators: lack of punctuality, withdrawal, exhaustion, excessive behavior, unhealthy eating habits Emotional indicators: depression, moodiness, loneliness, feeling overwhelmed, isolation - Describe allostasis and explain what occurs due to allostatic overload Allostasis: addresses complexities and variable levels of activity necessary to maintain or re-establish homeostasis. The body's response to stress. The process of achieving stability through physiological or behavioral change. +carried out by a superordinate set of systems that support homeostasis in light of environmental and lifestyle changes Allostatic overload: Refers to the state in which the normal allostatic processes wear out or fail to disengage or shut off; the physiological systems are not able to adapt contributing to long term effects that can be damaging to one’s health. - Explain why each of the following can occur due to stress: hypertension, stroke, coronary artery disease, gastrointestinal problems, immune suppression, diabetes mellitus Hypertension- caused by excessive catecholamine levels and bad stress coping like smoking and bad eating habits. As well as the supply of cortisol receptors in fat cells. Stroke- excessive catecholamine levels and the repeated or prolonged elevation of blood pressure, especially in combination with the effects of elevated cortisol levels. Coronary artery disease- increased platelet activity, resulting in clot formation and elevated serum lipid levels. Gastrointestinal problems- the sympathetic nervous system releases norepinephrine which reduces gastrointestinal motility and gastric acid secretion. Immune suppression- chronic activation of the stress mediators produces immunosuppression and increases the risk of infection and has been implicated in the development of autoimmune diseases. Diabetes Mellitus- when cortisol levels are increased by chronic stress of either a physiological or a psychological origin, this results in obesity; which is a risk factor for decreased effectiveness of glucose transport into the cells (insulin resistance), the pathophysiologic basis for diabetes type 2. - Define glycolysis, gluconeogenesis, glycogenolysis Glycolysis: breakdown of glucose by enzymes, releasing energy and pyruvic acid Gluconeogenesis: metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates Glycogenolysis: biochemical breakdown of glycogen to glucose. Takes place in the cells of muscle and liver tissues in response to hormonal and neural signals CHAPTER 4: CELL INJURY, AGING, AND DEATH - describe and give causes and examples of each of the following cell adaptations: atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia, anaplasia, neoplasia, necrosis Atrophy: cells shrink and reduce their differentiated functions in response to normal and injurious factor +Causes: disuse, denervation, ischemia, nutrient starvation, interruption of endocrine signals, persistent cell injury, aging +Example: muscles shrinking Hypertrophy: increase in cell mass accompanied by an augmented functional capacity in response to physiologic and pathophysiologic demands +Causes: increased cellular protein content +Example: working out more makes your muscles bigger; when one kidney is removed, the cells of other kidney divide at an increased rate Hyperplasia: increase in functional capacity related to an increase in cell number due to mitotic division +Causes: in response to increased physiologic demands or hormonal stimulation, persistent cell injury, chronic irritation of epithelial cells +Example: cells near your heart begin to reproduce so rapidly and abnormally that your organs are impaired due to their enlargement from excessive cell growth Metaplasia: replacement of one differentiated cell type with another +Causes: an adaptation to persistent injury, with replacement of a cell type that is better suited to tolerate injurious stimulation +Example: cigarette smoking that causes the mucus-secreting ciliated psuedostratified columnar respiratory epithelial cell that line the airways to be replaced by stratified squamous epithelium Dysplasia: disorganized appearance of cells because of abnormal variations in size, shape, and arrangement. Represents an adaptive effort gone astray. Significant potential to transform into cancerous cells, thus referred to as preneoplastic lesions +Causes: an adaptive effort gone wrong +Example: cervical dysplasia Anaplasia: loss of differentiation of cells and their orientation to each other, a characteristic of tumor cells +Causes: unknown? +Example: tumor cells Neoplasia: new, uncontrolled growth of cells that is not under physiologic control. Can be benign or malignant +Causes: multiple mechanisms +Example: granuloma Necrosis: irreversible cell death. Occurs as a consequence of ischemia or toxic injury and is characterized by cell rupture, spilling of contents into the extracellular fluid, and inflammation. Fours types of necrosis 1. Coagulative- most common! Caused by ischemic cell injury 2. Liquefactfive- the dissolution of dead cells occur very quickly, may form abscess or cyst. May be seen in the brain. 3. Fat- death of adipose tissue and usually results from trauma or pancreatitis, appears as a chalky white area of tissue. 4. Caseous- characteristic of lung tissue damaged by TB. - Describe ischemia, hypoxia, and hypoxemia along with why/when each condition occurs Ischemia: insufficient supply of blood to an organ, usually due to a blocked artery resulting in decreased oxygen and nutrient supplies to a tissue -Can be acute, due to a sudden reduction in blood flow. Cab be chronic, due to slowly decreasing blood flow Hypoxia: derives the cell of oxygen and interrupts oxidative metabolism and the generation of ATP in tissues -results from an inadequate amount of oxygen in the air, respiratory disease, ischemia, anemia, edema, or inability of the cells to use oxygen -occurs from severe asthma attack Hypoxemia: an abnormally low concentration of oxygen in the blood - when partial pressure of oxygen in blood is less than 60 mm Hg CHAPTER 7: NEOPLASIA - benign vs malignant tumors: terminology, appearance (gross and microscopic), growth, metastasis, necrosis, likelihood of recurrence, prognosis Malignant Tumor +can kill host if untreated +confirmed by invasive or metastasizing nature +tissue-specific differentiation (does not closely resemble tissue type of origin) -greater degree of anaplasia indicates aggressive malignancy +grows rapidly, may initiate tumor vessel growth, frequently necrotic, dysfunctional +may initiate tumor vessel growth (angiogenesis) +frequently necrotic +dysfunctional Benign Tumor +does not have potential to kill host, but may be life-threatening because of its location +does not invade adjacent tissue or spread to distant sites +Many are encapsulated +More closely resembles original tissue type +Grows more slowly, little vascularity, rarely necrotic, often retains original function - abnormal behavior of malignant cells Proliferate despite lack of growth-initiating signals from the environment Escape signals to die and achieve a kind of immortality in that they are capable of unlimited replication Lose their differentiated features and contribute poorly or not at all to the function of their tissue Genetically unstable and evolve by accumulating new mutations at a much faster rate than normal cells Invade their local tissue and overrun their neighbors Perhaps worst of all: gain the ability to migrate from their site of origin to colonize distant sites where they do not belong - metastasis: define/describe, pattern of spread, tumor markers, angiogenesis, grading/staging, most common organs where metastasis occurs, first place of metastasis for many cancers Metastasis: process by which cancer cells escape their tissue of origin and initiate new colonies of cancer in distant sites +specialized enzymes and receptors enable them to escape their tissue of origin and metastasize +specialized enzymes and receptors allow them to replicate at new site Pattern of spread +Generally spread via circulatory or lymphatic systems Tumor markers help identify parent tissue of cancer origin +Rely on some retention of parent tumor characteristics +Some released into circulation +Others identified through biopsy +Enzymes/proteins typically used as tumor markers +Help track tumor activity -Increased blood levels: progression and proliferation Angiogenesis +Process by which cancer tumor forms new blood vessels in order to grow +Usually does not develop until late stages of development +Triggers are not generally understood +Inhibition of angiogenesis is important therapeutic goal Grading and Staging of Tumors +To predict clinical behavior of malignant tumor and guide therapeutic management +Grading: histologic characterization of tumor cells -Degree of anaplasia -3 or 4 classes of increasing degrees of malignancy -Greater degree of anaplasia = greater degree of malignant potential +Staging -Location and patterns of spread within the host -Tumor size -Extent of local growth -Lymph node and organ involvement -Distant metastasis - generalized effects of cancer on the body +Depends on tumor location and extent of metastasis +Early stages may be asymptomatic +Tumor increases in size and spreads; more symptoms become apparent - effects of cancer therapies on the body: radiation, chemotherapy Radiation +Kills tumor cells by damaging nuclear DNA +Kills cells that are nonresectable due to location, missed by surgery, or undetected +May not kill cells directly, but initiates apoptosis +Small doses of radiation over several treatments (difficult to kill at once because cells on different cycles) +Some normal cells killed during radiation therapy Chemotherapy +Systemic administration of anticancer chemicals to treat cancers known or suspected to be disseminated in the body +Finds cancer cell targets in the body +Most are cytotoxic +Not selective for tumor cells (normal cell death may also occur) +Most effective on rapidly dividing cells +Several courses ensure all cancer cells killed +Serious side effect: bone marrow suppression +Promising approach is to inhibit angiogenesis by the tumor with antiangiogenic drugs CHAPTER 9: INFLAMMATION AND IMMUNITY - 4 major signs/symptoms of inflammation and what causes each to occur redness- (erythema) vasodilation and increased blood flow swelling- (edema) increased capillary permeability heat- (warm to touch) vasodilation and increased blood flow pain- increased capillary permeability and irritation of nerve endings - role of chemotaxis bring WBC to area - diagnostic tests indicative of inflammation leukocytosis, ^ CRP, ^ ESR, ^ plasma proteins, ^ cell enzymes, differential count - acute vs chronic inflammation; end result of chronic inflammation acute: mediators: vasodilation, increased capillary permeability, chemotaxis. Local effects: redness, heat, swelling, pain, may have exudate. Systemic effects: mild pyrexia, malaise, headache, anorexia Chronic: may develop after acute inflammation, insidious, less swelling and exudate, more lymphocytes, macrophages, and fibroblasts, more necrosis Cancer can be an end result of inflammation because inflammation relies on reactive oxygen which are secreted by neutrophils CHAPTER 10: ALTERATIONS IN IMMUNE FUNCTION Functions of all types of WBC’s: Basophils- Releases heparin to stop clotting, produce histamine to cause the blood vessels to dilate, help control inflammation, and kill parasites. Eosinophils- Kills parasites and helps control inflammation and allergic reactions Neutrophils- Removes small unwanted particles and materials from the blood Lymphocytes- Essential to the immune system and protect the body against the formation of cancer cells Monocytes- Destroys large unwanted particles in the bloodstream - Autoimmunity: what is going wrong with the immune system? Give examples An individual’s immune system recognizes its own cells as foreign and mounts an immune response that injures self tissues Ex. Systemic lupus erythematous, Addison disease, pernicious anemia - hypersensitivity: what is going wrong with the immune system? Normal immune response that is either: inappropriately triggered, excessive, or produces undesirable effects on the body - Type I: describe hypersensitivity problem, function/role of histamine, anaphylactic shock +Type I involves ability to respond to antigen and to produce an IgE antibody response +Released mediators cause inflammatory response +Example: allergies +Histamine: causes increased vascular permeability, vasodilation, uticaria, smooth muscle constriction, increased mucus secretion, pruritus Anaphylaxis: Life threatening because it causes systemic vasodilation combined with bronchoconstriction and edema Epinephrine needs to be administered immediately to open airways - Type II: describe hypersensitivity problem, give examples +Type II is a transfusion reaction or hemolytic disease of the newborn. The transfusion reaction is an individual that received blood from someone with a different blood group type. Hemolytic disease occurs during pregnancy hemolytic disease of the newborn Occurs during pregnancy. Rh negative mother is sensitized to her fetus’s Rh-positive red cell group antigens - Type III: describe hypersensitivity problem, give examples Antigen-antibody complexes activate complement cascade; phagocytic cells attracted to tissue EX: SCID EX: Lupus: autoimmune disease where the body’s immune system mistakenly attacks healthy tissue - Type IV: describe hypersensitivity problem, give examples Tissue damage resulting from a delayed cellular reaction to an antigen EX. TB - Mantoux skin test This skin test determines whether a person has TB or not. You inject a PPD into the forearm which produces a pale elevation of the skin 6 to 10 mm. Should be read between 48 and 72 hours after administration CHAPTER 11: MALIGNANT DISORDERS OF WHITE BLOOD CELLS - Type of cancers associated with: Philadelphia chromosome- Leukemia (CML) Reed-Sternberg cell- Hodgkin’s lymphoma Bence-Jones protein- urine test is used mainly to diagnose and monitor multiple myeloma, a type of cancer. An abnormal Bence-Jones test result is also linked with malignant lymphomas. These are cancers of the lymphatic system. Multiple myeloma is a blood cancer of the plasma cells. - overview of WBC cancers: - typical signs/symptoms of WBC cancer; what typically causes death to finally occur in these patients? S/S: Leukopenia (joint swelling and pain, weight loss, anorexia, hepatomegaly, splenomegaly), Anemia (pallor, fatigue, malaise, shortness of breath, decreased activity tolerance), Thrombocytopenia (a platelet count below 20,000 cells, petechiae, easy bruising, bleeding gums) These patients usually die because their white count is so low that they get many infections that their body can fight off - common complications, main treatment methods Complications: maintaining adequate nutrition status, infection, bone marrow transplantation failure Treatment: Chemotherapy, Complete remission (CR), intermittent chemotherapy may be continued for 2 to 3 years after initial induction of remission -chronic myeloid vs acute lymphoblastic vs multiple myeloma: Type Cell types affected, appearance of abnormal cells Age at onset, fast/acute or slow/insidiou s onset Clinical manifestations, prognosis/survival rate Treatment options Chronic Myeloid Characterized by malignant granulocytes that carry the Philadelphia chromosome (Ph+) 40-50 years High granulocyte count on the CBC, splenomegaly Treatment: Anti-bcr/abl therapy: reduce number of leukemic cells with bcr/abl type to undetectable levels Acute Lymphoblasti c Lymphoblasts : they look like immature lymphocytes Prognosis: poor survival time with chemotherapy, untreated has survival rate of 2 years, blast stage of CML has prognosis of 3-4 months Peak incidence: 3-7 years; 2nd peak: middle age Abrupt, bone pain, bruising, fever, infection, children may refuse to walk, loss of appetite, fatigue, abdominal pain, enlarged spleen, liver, lymph nodes Prognosis: 85% 5-year survival rate in children; 30% to 50% in adults Multiple Myeloma Mature, antibody-secr eting B Exclusively in adults; usually >40 years; plasma cells 30-95% of bone marrow, protein in urine, high serum Ca+ Allogenic BMT from suitable donor; autogenic BMT less effective Therapy: Chemotherapy for remission induction Post-remission chemo with/without stem cell transplant indicated for most patients Monoclonal antibodies may be used in patients whose tumors express specific antigens Antineoplastic agents: induce/maintain lymphocytes (plasma cells) median age 65 years. Men>women Onset: slow/insidious levels, 1st symptom is bone pain, anemia, recurrent infections, bleeding tendencies, renal insufficiency, “honeycomb” appearance in ribs, spine, skull, pelvis, Bence Jones protein: malignant plasma cells produce light-chain antibody fragments that accumulate in blood and urine remission in plasma cell proliferation, high-dose chemo followed by allogenic BMT, autologous stem cell transplantation CHAPTER 13: ALTERATIONS IN OXYGEN TRANSPORT - functions and normal ranges for RBCs, WBCs (total, not diff. count), and platelets Total blood volume: 75.5 ml/kg in men; 66.5 ml/kg in women Blood cells make up 45% of blood volume Plasma 55% of blood volume RBC- transport oxygen to tissues, remove CO2 from tissues, buffer blood pH WBC- protect the body by phagocytosis of microorganisms, form immune antibodies Platelets- form blood clots and control bleeding, release biochemical mediator involved in the hemostatic process - erythropoiesis: materials/substances needed, sites of production and destruction, functions of liver, spleen, and bone marrow in this process, fate of each part of hemoglobin and where it occurs Materials: adequate amount of iron, protein, vitamins, and minerals Production: Regulated by the concentration of hemoglobin in blood, in response to decreased hemoglobin the kidney secretes erythropoientin Destruction: Methemoglobin is removed by mononuclear phagocytic system, globin is broken down into amino acids and the iron is recycled, porphyrin is reduced by bilirubin, conjugated bilirubin is excreted in the bile as glucuronide - bicarbonate buffer system: identify each substance in the chemical equation; why is this equation important? - anemia: general description, relative vs absolute, general effects, clinical manifestations Anemia is a deficit of red cells. Low oxyen-carrying capacity leads to hypoxia Relative anemia: normal total red cell mass with disturbances in regulation of plasma volume Absolute anemia: actual decrease in numbers of red cells General Effects: -Reduction in oxygen-carrying capacity +Tissue hypoxia -Compensatory mechanism to restore tissue oxygenation +Increased heart rate, cardiac output, circulatory rate, and flow to vital organs +Increase in 2,3-DPG in erythrocytes and decreased oxygen affinity of hemoglobin in tissues Clinical Manifestations -Mild anemia (hemoglobin above 8 g/dl) +minimal symptoms +elderly with CV, pulmonary disease may have symptoms -Moderate/severe anemia (hemoglobin below 8 g/dl) +orthostatic hypotension/nonorthostatic +pallor +tachypnea +HA/lightheaded, fainting +angina, heart failure +nighttime leg cramps +tinnitus or roaring in ears +fatigue, weakness - compare and contrast types of anemia (aplastic, vit. B deficiency/pernicious, iron deficiency, sickle- cell) in terms of: causes, clinical manifestations and lab results Type Causes Clinical Manifestations Treatment Aplastic Toxic, radiant, or immunologic injury to the bone marrow stem cells Insidious onset Identify and avoid of further toxic exposure Late symptoms include weakness, fatigue, lethargy, pallor, dyspnea, palpitations, transient murmurs and tachycardia Pancytopenia and granulocytopeni a Type human leukocyte antigen (HLA) and ABO to identify serologically defined loci and potential donors Maintain minimally essential levels of hemoglobin and platelets Prevent and manage infection Administer immunosuppressiv e therapy or stimulate hematopoiesis and bone marrow regeneration Vitamin B/ Pernicious Inability to absorb B12, Autoimmune, gastromucosa is destrpyed by antibodies that attack the Premature graying, slight jaundice, smooth sore beefy red tongue, paresthesias, ataxia, Replacing nutritional deficiencies, get B12 injections Prognosis Iron Deficiency parietal cells, immunologic, surgical causes, cobalamin dietary deficiency neurological symptoms (confusion, AMS) Iron intake <2 mg/day (vegetarians, alcoholics), Fe malabsorption , Pregnancy, blood loss, RBC trauma Pallor, brittle nails, sore pale tongue, dizziness, hypoxia, pica (eat inedible thing), low ferritin Blood transfusion, Fe supplement, Vitmain C, improve diet (beef, chicken, egg yolk, turkey, whole grain) Thalassemia Sickle-Cell African descent Blood Loss Erythroblasti c Fetalis CHAPTER 14: ALTERATIONS IN HEMOSTASIS AND BLOOD COAGULATION - Clotting factors: site of production, effects of liver disease on clotting? Site of production- Liver The liver plays a central role in the clotting process, and acute and chronic liver diseases are invariably associated with coagulation disorders due to multiple causes: decreased synthesis of clotting and inhibitor factors, decreased clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis, and accelerated intravascular coagulation. - disseminated intravascular coagulation (DIC): general description, causes, why does excessive bleeding occur, lab results, treatment, is it life-threatening (why or why not)? DIC- life threatening acquired hemorrhagic syndrome in which clotting and bleeding occur simultaneously. Causes: trauma, malignancy, burns, shock, and abruption of placenta Lab results: fibrinogen level and platelet count decreased, increased bleeding time, elevated PT/INR/aPTT, elevated D-dimer/fibrin split products Treatment: removal/correction of underlying cause, support major organs, fresh frozen plasma, packed red blood cells, platelets, or cryoprecipitate, heparin used to minimize further consumption of clotting factors Lab Tests: Know what each detects. ABG- arterial blood gases, blood gas measurments are used to evaluate a person’s lung function and acid/base balance. CBC- complete blood count, test used to evaluate your overall health and detect a wide range of disorders, including anemia, infection and leukemia. CRP- C- reactive protein, blood test marker for inflammation in the body ESR- erythrocyte sedimentation rate, detects inflammation associated with conditions such an infections, cancers, and autoimmune diseases. FERRITIN- measures the amount of ferritin in a person’s blood stream. Measures iron stores in the body. Hb- detects amount of red blood cells which carry oxygen to your bodies organs and tissues (detects anemia) Hct- measures the proportion of red blood cells in your blood. INR/PT- detects coagulation LDCMCH- used in the detecting of the cause of anemia MCHC-used in the detection of the cause of anemia MCV- used in the detection of the cause of anemia PaCO2- detects acid base balance PaO2- detects acid base balance PItPT- detects how long it takes for a clot to form RBC- used to detect or monitor disease. RBC carry oxygen. WBC- detects that there is a disease or condition affecting wbc. WEEKS 3-4: CHAPTER 15: ALTERATIONS IN BLOOD FLOW - understand blood flow through the heart, to and from the lungs, and to and from the body: - list, in order, all heart chambers, heart valves, and key vessels (pulmonary trunk, left and right pulmonary arteries, left and right pulmonary veins, aorta, coronary arteries, coronary sinus, superior vena cava, inferior vena cava, tricuspid valve, bicuspid/mitral valve, aortic valve, pulmonary valve) R atrium → tricuspid valve → R ventricle → pulmonary valve → pulmonary trunk → R + L pulmonary arteries → lung capillaries → R + L pulmonary veins → L atrium → bicuspid/mitral valve → L ventricle → aortic valve → aorta →Heart capillaries, lower body capillaries, upper body capillaries - Vessels: - which type controls BP/SVR? factors that influence SVR? Arterioles Factors: vessel length, vessel radius, blood viscosity - which vessel carries blood under highest pressure? in which type does exchange of materials occur? Arteries carry blood under highest pressure. Exchange of materials occurs in the capillaries. - Define edema and lymphedema Edema: swelling caused by fluid retention Lymphedema: impairment of lymphatic flow allowing fluid to collect in the interstitium - Blood vessel obstructions: - thrombus vs embolus Thrombus: stationary blood clot formed within a vessel or heart chamber. Embolus: traveling clot - Thrombosis/embolism in an artery or vein: clinical manifestations, effects, life-threatening locations – why would it be life-threatening? Thrombosis: Arterial- ischemia. Intermittent claudication, cool, cyanotic Venous- edema. None or life threatening ( pulmonary embolism) calf/groin tenderness, swelling Plebitis- inflammation in vein Thrombophlebitis- inflammation with a clot in a vein. Embolus: Embolus leaving L ventricle = ischemic stroke. Differs on brain area affected, loss of cognitive function, motor changer, and different levels of sensory loss. Embolus leaving R ventricle= pulmonary embolus. Acute onset of SOB, increased RR, chest pain, SUDDEN DEATH. - Arteriosclerosis/Atherosclerosis: - formation of an atheroma and major locations where they typically occur Large and medium sized arteries, Most frequently the coronary, cerebral, carotid, and femoral arteries and the aorta. - causes and risk factors including tobacco effects, complication and sequelae (Risk factors) Modifiable: -smoking -elevated BP -obesity -ineffective stress management -glucose intolerance -decreased physical activity Non-modifiable: -age -gender -ethnicity -heredity Hypertension is both a risk factor for the development of atherosclerosis and an outcome of it.23 Increases in both systolic and diastolic blood pressure are associated with an increased incidence of atherosclerosis. Cholesterol, the lipoproteins, and triglycerides are important in the discussion of atherosclerosis. Obesity, denied as a body weight 30% or greater than ideal, is thought to be a contributing risk factor for atherosclerosis in that it may accelerate the process - collateral circulation: the alternate circulation around a blocked artery or vein via another path, such as nearby minor vessels. - Aneurysms: - description, typical locations, diagnosis Description: localized arterial dilations, bulge outwards True aneurysms -saccular: one sided balloon -fusiform: both sides balloon out -berry: balloon has a stem/neck False aneurysms -one layer unaffected Typical locations: frequently found in cerebral circulation and thoracic and abdominal aorta Clinical Manifestations: -cerebral: high ICP, hemorrhagic stroke -aortic: sudden severe tearing pain, radiates into back/abdomen, shock Tests: -cerebral: CT, MRI, cerebral angiography -aortic: CT, TEE (transesophageal echocardiogram) - Acute arterial occlusion: description, causes, locations where they usually occur, classic signs/symptoms Absence of arterial circulation- emergency Thrombi/emboli or mechanical compression Classic signs and symptoms (6 Ps) -pallor -paresthesia -paralysis -pain -polar- cold to touch -pulseless - Venous flow alterations: - varicose veins: description, most common vein affected Impaired venous return results in superficial, darkened, raised, and tortuous veins Greater saphenous vein most commonly affected - deep vein thrombosis (DVT): description, why can it be life-threatening? Thrombus in a deep vein of the lower extremity. May be asymptomatic Previous DVT is risk for further hypercoagulation. If it breaks free, it can travel through your body and eventually lodge in the arteries of the lungs, blocking blood flow. This is a life-threatening emergency called a pulmonary embolism. CHAPTER 16: ALTERATIONS IN BLOOD PRESSURE - Cardiac output (CO): - CO vs SV including units of measurement CO: the amount of blood pumped by each ventricle in 1 minute (mL) SV: the amount of blood ejected from each ventricle with each contraction (mL) - how is CO related to SV and heart rate (HR) – give mathematical equation CO = HR x SV - effects on CO when: HR increases and SV stays the same, SV decreases and HR stays the same, cardiac diseases/conditions HR inc. SV same: The CO is going to increase. Example can be during exercise SV dec. HR same: When the HR stays the same, cardiac output is going to decrease. Example can be an MI - Blood pressure (BP): - how is BP related to CO, systemic vascular resistance (SVR), HR, and SV BP = CO x PR (SVR), CO = HR x SV - effect on BP of: systemic vasoconstriction, systemic vasodilation, atherosclerosis, bradycardia and tachycardia, ADH and aldosterone (stress response), renin, sitting up too quickly after lying down, smoking, kidney disease vasoconstriction= high BP vasodilation= low BP atherosclerosis= high BP bradycardia= low BP, tachycardia= high BP ADH= high BP aldosterone= high BP Renin= high BP Sitting up too quickly= low BP Smoking= high BP Kidney disease= high BP - function of each of the following in BP regulation: sympathetic nervous system, parasympathetic nervous system, renin-angiotensin-aldosterone-system (RAAS) SNS= increases BP PNS= decreases BP RAAS= increases BP - BP ranges for normal, pre-hypertension, and hypertension Normal= 120/80, Prehypertension= 120-139/80-89, Stage 1 hypertension= 140-159/90-99, Stage 2 hypertension= >160/>100 - How does compensation occur for changes in CO and BP? If CO decreases, HR increases and the opposite. - Primary hypertension: - description, cause, risk factors, effects of long-term/prolonged hypertension, treatment subtypes: -isolated systolic hypertension >140/<90 -isolated diastolic hypertension <140/>90 -combined systolic and diastolic hypertension: > prehypertension levels Cause: idiopathic Risk factors: -Nonmodifiable: -family history -age -ethnicity/genetics -modifiable -dietary factors -sedentary lifestyle -obesity/weight gain -metabolic syndrome -high blood glucose/diabetes -high total cholesterol -alcohol and smoking -childhood and adolescent (intrauterine) -maternal smoking -pregnancy induced hypertension -dietary habits -low birth rate followed by rapid growth in both height and weight -lower socioeconomic level of mother -inadequate intake of calcium by pregnant mother -breastfeeding seems to reduce the risk Effects: -silent killer: damage already occurred to organs before diagnosis is made -end-organ damage -renal failure, stroke, heart disease -damage to arterial system and acceleration of atherosclerosis lead to CV disease -high myocardial work= heart failure -glomerular damage= kidney failure -affects microcirculation of the eyes -high pressure in cerebral vasculature= hemorrhage Treatment: -lifestyle modifications are first and most important -weight loss, exercise, DASH diet, alcohol moderation, dec. Na+ intake -drug therapy for hypertension affects HR, SVR, and/or stroke volume - Difference between primary and secondary hypertension Primary hypertension- has no identifiable cause. Secondary hypertension- has an identifiable cause. Ex: renal artery stenosis, pregnancy, obesity, hyperaldosteronism (most common cause) CHAPTER 18: ALTERATIONS IN CARDIAC FUNCTION - Coronary heart disease (CHD)/coronary artery disease (CAD): - description, risk factors, arterial changes insufficient delivery of oxygenated blood to the myocardium due to atherosclerotic coronary arteries Risk factors: atherosclerosis, possible microcirculation abnormalities Changes: Can lead to cardiac ischemia through thrombus formation, coronary vasospasm, endothelial cell dysfunction - stable angina pectoris: description, causes, effects on the heart and if they are transitory or permanent, pattern of onset, treatment -most common -characterized by stenotic atherosclerosis coronary vessels -onset of angina pain is generally predictable and elicited by similar stimuli each time -relieved by rest and nitroglycerin - no permanent damage - myocardial infarction: -total block -chest pain (unrelieved) and radiating - prolonged -Irreversible - STEMI vs NSTEMI STEMI: ST elevation on ECG. patients with chest pain and evidence of acute ischemia -candidates for acute reperfusion therapy NSTEMI: patients presenting with symptoms of unstable angina and no ST elevation on the ECG -candidates for antiplatelet drugs - scar tissue formation and its effects on cardiac muscle Clinical Manifestations: -severe crushing, excruciating chest pain that may radiate to the arm, shoulder, jaw, or back -accompanied by nausea, vomiting, diaphoresis (sweating), shortness of breath -lasts more than 15 minutes and is not relieved by rest or nitroglycerin -asymptomatic MI: silent MI -Women, the elderly, and patient with diabetic neuropathies: -atypical symptoms including fatigue, nausea, back pain, and abdominal discomfort -ECG changes: ST-segment elevation, large Q waves, and inverted T waves Serum marker changes -myoglobin, troponin, lactate dehydrogenase, and creatine kinase -increased CK-MB and troponin I and T - effect of MI on CO, compensatory mechanisms MI leads to drop in CO, triggering compensatory responses including sympathetic activation -SNS activation leads to increased myocardial workload by increasing: -HR -Contractility -BP - basic treatment; possible sequelae -decreasing myocardial oxygen demand -sympathetic antagonists, rest, HR control, pain relief, afterload reduction -increasing myocardial oxygen supply -thrombolysis, angioplasty, coronary bypass grafting -monitoring and managing complications -early detection and management of dysrhythmias and conduction disorders; continuous ECG monitoring - sudden cardiac arrest: description, type of associated arrhythmia -Also called sudden cardiac death -Unexpected death from cardiac causes within 1 hour of symptom onset -Use of external defibrillators and CPR has increased survival -Lethal dysrhythmia (such as ventricular fibrillation) is usually the primary cause - pericardial diseases: - cardiac tamponade: description, effects of pericardial effusion on heart contraction, why is it life- threatening? -when fluid accumulation in the pericardial sac is large/sudden it can lead to external compression of the heart chambers such that filling is impaired -Manifestations include: -reduced stroke volume -compensatory increases in HR -pulsus paradoxus -hypotension, distended neck veins and muffled heart sounds- called Beck’s triad -Treatment: pericardiocentesis CYANOTIC : RIGHT TO LEFT ACYANOTIC: LEFT TO RIGHT CHAPTER 19: HEART FAILURE AND DYSRHYTHMIAS: COMMON SEQUELAE OF CARDIAC DISEASES - congestive heart failure: - descriptions, causes (including other diseases), common manifestations, FACES Inability of heart to maintain sufficient cardiac output to meet metabolic demands of tissues and organs Results in congestion of blood flow in the systemic or pulmonary venous circulation, inability to increase cardiac output to meet the demands of activity or increased tissue metabolism Most common reason for hospitalization in those >65 years of age Cause: most common is myocardial ischemia followed by hypertension and dilated cardiomyopathy Manifestations: dyspnea, pulmonary rales, cardiomegaly, pulmonary edema, S3 heart sound, and tachycardia Results from impaired ability of myocardial fibers to contract, relax, or both FACES (fatigue, activity limitation, congestion, edema, shortness of breath) - compensatory mechanisms and explain why they eventually cause further heart damage helpful in restoring cardiac output toward normal Eventual consequences: SNS activation, increased preload, myocardial hypertrophy - left and right sided failure: - explain backward (where does blood back up) and forward (what areas are affected by impaired blood flow) effects Type Backward Effects Forward Effect Left-Sided HF Results in accumulation of blood within the pulmonary circulation, pulmonary congestion, and edema Results in insufficient CO with diminished delivery of oxygen and nutrients to peripheral tissues and organs Dyspnea, dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea Acute cardiogenic pulmonary edema: life threatening condition Cough, respiratory crackles (rales), hypoxemia, and high left-atrial pressure, cyanosis Right-Sided HF Due to congestion in the systemic venous system Cause low output to left ventricle leading to low CO Edema, ascites, jugular veins distended, impaired mental functioning, hepatomegaly, splenomegaly Hepatojugular reflux test - why does biventricular heart failure occur? what further problems does this cause? Result of primary left-sided HF progressing to right-sided HF Reduced CO Pulmonary congestion due to left-sided HF Systemic venous congestion due to right-sided HF - cardiac dysrhythmias Most severe dysrhythmias and why they are life-threatening Ventricular tachycardia: three or more consecutive ventricular complexes at a rate greater than 100 beats/min, ECG depicts a series of large, wide, undulating waves, Pwaves are not associated with the QRS complexes Ventricular fibrillation: rapid, uncoordinated cardiac rhythm resulting in ventricular quivering and lack of effective contraction, ECG is rapid and erratic with no identifiable QRS complexes Atrioventricular block: problem between the sinus impulse and ventricular response -3 types: -1st degree (usually no treatment required) -2nd degree (types I and II) -type I (Wenckebach, Mobitz): characterized by progressive prolongation of the PR interval until one P wave is not conducted; associated with AV nodal ischemia -type II: identified by a rhythm showing consistent PR interval with some noncunducted P waves; more serious because has a tendency to progress to complete AV (third degree) block -3rd degree (complete) -diagnosed when there is no apparent associated between atrial and ventricular conduction; is serious, as it can lead to slow ventricular rhythm and poor CO CLASSES OF MEDICATIONS FOR CARDIAC DISORDERS: On paper. CHAPTER 20: SHOCK - general description and common factor for all types of shock Common factor among all types of shock is hypoperfusion and impaired cellular oxygen utilization. This decreases CO, maldistribution of blood flow and decreased blood oxygen content Cardiogenic: inadequate cardiac output despite sufficient vascular volume, usually result of severe ventricular dysfunction associated with MI Obstructive: circulatory blockage, such as a large pulmonary embolus or cardiac tamponade, cardiac output Hypovolemic: loss of blood volume as a result of hemorrhage or excessive loss of extracellular fluids Distributive: greatly expanded vascular space because of inappropriate vasodilaion - description of the 3 clinical stages; clinical manifestations Compensatory stage: homeostatic mechanisms are sufficient to maintain adequate tissue perfusion despite a reduction in CO Progressive stage: marked by hypotension and marked tissue hypoxia -lactate production increases with anaerobic metabolism -lack of ATP leads to cellular swelling, dysfunction, and death -cellular and organ dysfunction result from oxygen-free radicals, release of inflammatory cytokines, and activation of the clotting cascade Refractory stage - causes of cardiogenic, obstructive, hypovolemic, and distributive (including anaphylactic, neurogenic, septic) Cardiogenic: result of severe ventricular dysfunction associated with MI Obstructive: results from mechanical obstructions that present effective cardiac filling and stroke volume. Common causes include pulmonary embolism, cardiac tamponade, and tension pneumothorax Hypovolemic: results from inadequate circulation blood volume precipitated by hemorrhage, burns, dehydration or leakage of fluid into interstitial spaces (most common cause: external hemorrhage) Distributive: -Anaphylaxis: antibiotic therapy, in particular B-lactams, peanuts and tree nuts, insect stings, and snake bites -Neurogenic: medullary depression (brain injury, drug overdose) or lesions of sympathetic nerve fibers (spinal cord injury) -Septic: gram-negative and gram-positive bacteria, fungal infections CHAPTER 21: RESPIRATORY FUNCTION AND ALTERATIONS IN GAS EXCHANGE Respiratory system overview Structures: Larynx- A cartillaginous organ containing vocal cords for sound production. Trachea- Flexible tube of C shaped cartilage to allow air to reach lungs. Bronchi- Branches of the trachea to allow passage of air to lungs Bronchioles- Tubes connecting bronchi to alveoli. Alveoli- Millions of tiny sacs within the vertebrate lungs where gas exchange occurs. Simple squamous epithelium allow O2 and CO2 to diffuse into and out of the alveoli and are surrounded by blood capillaries Epiglottis- a flap of cartilage at the root of the tongue which is depressed during swallowing to cover the opening of the windpipe. Uvula- closes off the nasopharynx, preventing food from entering the nasal cavity. Mechanism of normal inspiration and expiration. During inspiration, chest wall muscles contract, elevating the ribs as the diaphragm moves downward, creating a negative intrapleural pressure. During expiration, lung deflates passively because of elastic recoil and relaxation of the diaphragm. At the end of normal expiration, alveoli still have some gas remaining, known as functional residual capacity. Surfactant decreases surface tension, allowing the alveoli to open easily with each breath. Lack of surfactant can cause the alveoli to collapse leading to atelectasis. Importance of surfactant in fetal development: Until about 36 weeks of gestational age, a fetus is in the saccular phase of lung development. During this time, surfactant production begins in the lungs. Surfactant is a soapy substance that helps keep delicate lung tissue from sticking to itself and tearing during exhalation or if the lungs are compressed. Surfactant is particularly important during delivery, as it allows the lungs to drain of amniotic fluid and fill with air properly. Premature infants are susceptible to respiratory problems and lung collapse if they are born before sufficient surfactant forms. Pulmonary volumes: Tidal volume- amount of air that moves in and out of the lungs with each breath. The normal amount of tidal volume is (500 ml.) Vital capacity- total amount of air involved with tidal volume, inspiratory reserve volume, and expiratory reserve volume. (4,500 ml) Residual volume- the amount of air that cannot be voluntarily expelled from the lungs. (1,500ml) Describe how gas exchange occurs in the lungs and at the tissues External respiration: During external respiration (Pulmonary gas exchange), dark red blood flowing through the pulmonary circuit is transformed into the scarlet river that is returned to the heart for distribution by systemic arteries to all body tissues. Color change is caused by O2 pick up and binding to hemoglobin in RBC, but Co2 exchange (unloading) happens equally fast. Internal respiration: Internal respiration involves capillary gas exchange in body tissues. The gas exchanges that occur between blood and alveoli and between blood and tissue cells take place by simple diffusion. Role of carbon dioxide in triggering breathing Explain how the lungs can control pH, including normal serum pH range, acidosis/alkalosis An increase in breathing rate should decrease CO2 concentration and increase oxygen concentration leading to a decrease in hydrogen ions and a pH decrease until homeostasis is met. When the CO2 reacts with water to produce carbonic acid the carbonic acid then dissociates into H+ ions and HCO3- ions. The H+ ions increase the acidity of the blood. -breath FASTER to get rid of CO2 if LOW pH -CO2 forms carbonic acid in blood -Breath SLOWER to retain CO2 if HIGH pH -CO2 combines with water to form carbonic acid in the blood Pulmonary function tests/spirometry Test to access pulmonary mechanics under dynamic conditions Most common test performed in assessing lung function and performed at bedside Consists of a series of FVC maneuvers (measure both volume and flows) Secondary pulmonary hypertension -Greater than 25 Primary htn- (idiopathic) pulmonary HTN is rapidly progressive and occurs more often in women; long term prognosis is poor and medical tx usually ineffective Secondary htn- (from a known disease) 3 mechanisms: increased pulmonary blood flow, increased resistance to blood flow, and increased left atrial pressures. -initially , walls of small pulmonary vessels thicken from an increase in the muscle; internal layer of pulmonary artery wall becomes fibrotic. Sustained pulmonary HTN results in formation of a network of blood vessels (plexiform) that impede blood flow. Clinical manifestations: Vary according to the severity and duration of the cause. Exercise intolerance, fatigue, syncope, hemoptysis, chest pain on exertion, increasing dyspnea, hoarse voice from compression of laryngeal nerve by engorged pulmonary artery (ortner’s syndrome) Pulmonary venous thromboembolus: Thrombus dislodged from point of origin by direct trauma, exercise, muscle action, changes in blood flow. Virchow’s triad factors causing thromboemboli formation include: Venous stasis/sluggish blood flow, hypercoagulability, damage to the venous wall Risk factors: immobility, trauma, pregnancy, cancer, heart failure, and estrogen use. Clinical manifestations: depends on size of thrombus. Usually includes restlessness, apprehension, anxiety, dyspnea, tachycardia, tachypnea, chest pain (on inspiration) and hemoptysis. CHAPTER 22: OBSTRUCTIVE PULMONARY DISORDERS Asthma A reversible airway obstruction. Causes airway inflammation. Extrinsic- allergic, pediatric onset Intrinsic- non-allergic, adult onset Pathogenesis of allergic asthma: describe airway inflammation/cause of obstruction Exposure to a specific antigen that has previously sensitized mast cells in airway mucosa; antigen reacts with the antibody releasing chemical mediator substances. Normal respiratory epithelium replaced by goblet cells, resulting in mucosal edema, inflammatory exudates, and hyperresponsiveness of the airway. (bronchoconstriction and leakage from increased microvascular permeability) Clinical manifestations, including severe attack and status asthmaticus Wheezing, feeling of tightness of chest, dyspnea, cough (dry or productive), increased sputum production (thick, tenacious, scant, and viscid), hyperinflated chest, decreased breath sounds. Severe attack: use of accessory muscles or respiration, intercostal retractions, distant breath sounds with inspiratory wheezing, orthopnea, agitation. Diagnosis: radiology, pulmonary function test changes, abg changes Radiologic finding- hyperinflation with flattening of the diaphragm. Pulmonary function test- forced expiratory volumes decreases, peak expiratory flow rate (PEFR): determines index of airway function, ratio of FEV/FVC <75% Abg- normal during mild attack. Respiratory alkalosis and hypoxemia as bronchospasm increases in intensity. PaCO2 elevation: sign that patient is getting worse. Treatment Avoid triggers: Environmental control- dust control, removal of allergens, air purifiers, air conditioners. Preventative- stop smoking, avoid second-hand smoking, aerosols, odors, early tx for respiratory infections. Medications: Bronchodilators- epinephrine (subcutaneous terbutaline, aminophylline) Intravenous corticosteroids- (mainstay of therapy) Oxygen therapy with or without mechanical ventilation. Chronic obstructive pulmonary disorder (COPD) Chronic bronchitis vs emphysema - Description and etiology; reversible or not Chronic bronchitis- Type B COPD, “blue bloater”. Hypersecretion of bronchial mucus. Chronic of recurrent productive cough >3 months. Persistent, irreversible when paired with emphysema. Emphysema- Type A COPD, “pink puffer”. Destructive changes of the aveolar walls without fibrosis. Abnormal enlargement of the distal air sacs. Damage is IRREVERSIBLE. - Explain why “blue bloater” or “pink puffer” Blue bloater- excess body fluids, chronic cough, SOB on exertion, increased sputum, cyanosis (late sign). Pink puffer- use of accessory muscles to breathe, pursed lip breathing, minimal or absent cough, leaning forward to breathe, barrel chest, digital clubbing, dyspnea on exertion (late sign) Pathogenesis, including airway changes, gas exchange, and complications/sequelae Chronic bronchitis- chronic inflammation and swelling of the bronchial mucosa resulting in scarring. Increased bronchial wall thickness. Emphysema- release of proteolytic enzymes from neutrophils and macrophages leading to aveolar damage. Reduction in pulmonary capillary bed. Exchange of O2 and CO2 between alveolar and capillary blood impaired. Clinical manifestations Chronic bronchitis :overweight, SOB on exertion, excessive sputum, chronic cough (worse in the am), evidence of excessive body fluids (edema), cyanosis. Emphysema: thin, failure to thrive, use of accessory muscles, pursed lip breathing, cough, digital clubbing, barrel chest. Diagnosis Chronic bronchitis - Chest Xray - increased bronchial vascular markings, congested lung fields, enlarged horizontal cardiac silhouette. Pulmonary function test- normal total lung capacity, increased residual volume, decreased FEV ABG- elevated PaCO2, decreased PO2 Emphysema - Chest Xray- hyperventilation, low flat diaphragm, presence of blebs or bullae, narrow mediastinum, normal or small “vertical” heart. Pulmonary function test- increased functional residual capacity, increased RV, TLC, decreased FEV, FVC. ABG- mild decrease in PaO2, normal PaCO2. Treatment Chronic bronchitis - Medications: inhaled short acting B2 antagonists, inhaled anticholinergic bronchodilators, cough suppressants, antimicrobial agents, inhaled/oral corticosteroids, theophylline products (bronchodilators). - Low dose O2 therapy - Mechanical ventilation may be necessary - Management- smoking cessation, reduction to exposure of irritants, adequate rest, proper hydration, physical reconditioning ( treadmill/stationary bike, alternating rest and exercise, walking best exercise.), flu vaccines. Emphysema - Medications: inhaled short acting B2 antagonists, inhaled anticholinergic bronchodilators, cough suppressants, antimicrobial agents, inhaled/oral corticosteroids, theophylline products (bronchodilators). - Low dose O2 therapy - Mechanical ventilation may be necessary Cystic Fibrosis Hypersecretion of abnormal, thick mucus that obstructs exocrine glands and ducts. Dysfunction of CFTR gene. This results in alteration in chloride and water transport across epithelial cells. Primarily affects the pancreas, intestinal tract, sweat glands, and lungs, and in males causes infertility. High concentrations of sodium and chloride in sweat, salivary, and lacrimal secretions. Causes airway obstruction, atelectasis, and hyperinflation and also decreases ciliary action. - - - Clinical manifestations - Cough - Thick, tenacious sputum - Recurrent pulmonary infections - Dyspnea, tachypnea - Sternal retractions - Unequal breath sounds - Crackles and rhronchi - Barrel chest - Digital clubbing (late sign) - Stetorrhea ( fatty stools) - Anorexia - Decreased growth in children Diagnosis - ABG- hypoxemia and hypercapnia - Chest xray- patchy atelectasis, bronchiectasis, cystic lung fields - PFT- decreased VC, airflow, TV, increased airway resistance, functional residual capacity Treatment - Aggressive tx of respiratory infections, postural drainage and chest physiotherapy (priority), forced expiratory technique - Nutritional therapy: unrestricted fat consumption, high protein, vitamin supplements (A,K,D,E), pancreatic enzymes, may need enteral feedings or IV feedings - Medications: bronchodilators, antibiotics, flu vaccine - Heart lung transplant CHAPTER 23: RESTRICTIVE PULMONARY DISORDERS General differences between obstructive and restrictive disorders The Difference Between Obstructive and Restrictive Lung Disease. The term obstructive lung disease includes conditions that hinder a person's ability to exhale all the air from their lungs. Those with restrictive lung disease experience difficulty fully expanding their lungs. Acute/ adult respiratory distress syndrome (ARDS) - - Damage to the alveolar-capillary membrane. Causes widespread protein-rich alveolar infiltrates and severe dyspnea. Occurs in association with other pathophysiological processes. Associated with a decline in PaO2 that is refractory (does not respond) to supplemental oxygen therapy. Causes - Severe trauma - Sepsis - Aspiration of gastric acid - Fat emboli syndrome - Shock Flooding of the alveoli with proteinaceous fluid Leads to the development of protein-rich pulmonary edema (noncardiogenic) Triggers the immune system to activate the complement system and to initiate neutrophil sequestration in the lung. Injury to pulmonary circulation Atelectasis and decrease in lung compliance from lack of surfactant Fibrosis of hyaline membrane Severe Hypoxemia Clinical Manifestations - History of precipitating event that has led to low blood volume state (shock) 1 or 2 days prior to the onset of respiratory failure - Early: sudden marked respiratory distress, slight increase in pulse rate, dyspnea, low PaO2, shallow rapid breathing - Late: tachycardia, tachypnea, hypotension, marked restlessness, frothy secretions, crackles, rhonci on auscultation, use of accessory muscles, intercoastal and sternal retractions, Cyanosis. Infant respiratory distress syndrome (IRDS) - The absence or deficiency of surfactant. HALLMARK: hypoxemia that is refractory to increasing levels of oxygen supplementation. Decreased or altered surfactant Atelectasis or alveolar collapse Decrease pulmonary blood flow Hypoventilation Hemorrhagic pulmonary edema Clinical manifestations: - Early : shallow respirations, diminished breath sounds, intercostal/subcostal/sternal retractions, flaring of nares, hypotension, bradycardia, peripheral edema, low body temp, oliguria, tachypnea (60-120 breaths/min) Late : frothy sputum, central Cyanosis, expiratory grunting sound, paradoxical respirations (seesaw movement of chest wall) Pneumothorax - Accumulation of air in the pleural space Open “sucking” chest wall wound - Primary pneumothorax - Spontaneous - Occurs in tall, thin men 20 to 40 yr old - No underlying disease factors - Cigarette smoking increases risk - Secondary pneumothorax - Results of complications from pre-existing pulmonary disease - Tension pneumothorax - Traumatic origin - Results from penetrating or nonpenetrating injury - May also be from iatrogenic causes - Medical emergency - Results from buildup of air under pressure in pleural space - Air enters pleural space during inspiration but cannot escape during expiration. - Decreases venous return and cardiac output. - Clinical Manifestations - Small pneumothoraces are usually not detectable on physical exam - Tachycardia - Decreased or absent breath sounds on affected side - Hyperresonance - Sudden chest pain on affected side - Dyspnea - Tension and large spontaneous pneumothorax are emergency situations. - Severe tachycardia - Hypotension - Tracheal shift to contralateral (opposite) side - Neck vein distension - Subcutaneous emphysema Explain the function of inserting a chest tube A chest tube can help drain air, blood, or fluid from the space surrounding your lungs, called the pleural space. Chest tube insertion is also referred to as chest tube thoracostomy. It's typically an emergency procedure. Pleural Effusion - - - Pathologic collection of fluid or pus in pleural cavity as result of another disease process - Normally, 5-15 ml of serous fluid is contained in pleural space Five major types - Transudates - Low in protein - Associated with severe heart failure or other edematous states - Exudates - High in protein - Causes: malignancies, infections, pulmonary embolism, sarcoidosis, post myocardial infarction syndrome, pancreatic disease. - Emphysema due to infection in the pleural space - High protein exudative effusion - Hemothorax - Presence of blood in pleural space - Result of chest trauma - Contains blood and pleural fluid: hemorrhagic - Chylothorax or lymphatic - Exudative process that develops from trauma Causes: - Imbalance in pressure associated with fluid formation exceeding fluid removal Clinical Manifestations - May be asymptomatic with <300 ml of fluid in pleural cavity - Dyspnea - Decreased chest wall movement - Pleuritic pain (sharp, worsens with inspiration) - Dry cough - Absence of breath sounds - Dullness to percussion (primary finding) - Contralateral tracheal shift (massive effusion) Treatment - Directed underlying cause and relief of symptoms - Tension and spontaneous pneumothorax are medical emergencies requiring treatment to remove pleural air and re expand lung - Thoracentesis if large amount of effusion - U/S useful for thoracentesis guidance - Thoractomy - Control bleeding Pneumonia Inflammatory reaction in the alveoli and interstitium caused by an infectious agent. - High risk - Elderly - Those with diminished gag reflex - Seriously ill - Hospitalized patients (bedridden) - Hypoxic patients - Immune compromised patients Major causative organisms Anaerobic Bacteria - Present as a lung abscess, necrotizing pneumonia, or empyema; usually caused by aspiration of normal oral bacteria into the lung Mycoplasma pneumonia - Commonly seen in the summer and fall in young adults; common between the ages of 5 and 20 Opportunistic pneumonias (fungal) - Pneumocytis jiroveci - Opportunistic fungal infection - Common in patient with cancer or HIV Aspergillus - Opportunistic fungal infection - Released from walls of old buildings under reconstruction Pathogenesis - Acquired when normal pulmonary defense mechanisms are compromised Viral pneumonia doesn’t produce exudative fluids Clinical Manifestations - Crackles (rales) and bronchial breath sounds over affected lung tissue - Chills - Fever - Cough, purulent sputum - Viral - Upper respiratory prodrome - fever , nonproductive cough, hoarsness, coryza accompanied by wheezing/rales - Chlamydia pneumonia - Cough, tachypnea, rales, wheezes, and no fever - Mycoplasma - Fever Cough HA Malaise Diagnosis - Chest Xray shows ( parenchymal infiltrates) white shadows in involved area Sputum C&S from deep in lungs Bloodwork for WBC >15,000 (acute bacterial) Treatment - Antibiotic therapy Pulmonary Tuberculosis - - is an infectious pulmonary disease caused by tubercle bacilli, bacterial airborne transmitted through droplet nuclei and emitted when coughing, sneezing, laughing, singing. High Risk population - Prior infection - malnourishment/immunosuppression - Living in overcrowded condition - Incarcerated persons - Immigrants - Elderly Causative organism - Mycobacterium tuberculosis - Infects lungs and lymph nodes - Infection - Inhalation of small droplets containing bacteria - Droplets expelled with cough, sneeze, talking - Primary vs Reacting - Primary (usually clinically/radiographically silent) may lie dormant for years or decades - Reacting - May occur many years after primary infection - Impaired immune system causes reactivation - HIV, corticosteroid use, silicosis, and diabetes mellitus have been found to be associated with reactivation - Pathologic manifestation is GHON tubercle or complex - Clinical Manifestations - History of contact with infected - - Low grade fever Chronic cough (most common) as disease progresses becomes productive with purulent sputum - Night sweats - Fatigue - Weight loss - Malaise - Anorexia - Apical crackles (rales) - Bronchial breath sounds over region of consolidation - Malnourished Diagnosis - Sputum C&S (definitive diagnosis) - DNA or RNA amplification techniques (diagnosis) - PFTs - CXS - Nodules with infiltrates in apex and posterior segments - TB skin test (mantoux or PPD) - Doesn’t distinguish between current disease or past infection - False positive PPD results may occur in persons with other mycobacterial infections or if they have received bacille Calmette Guerin vaccine. - Treatment - Antibiotics CHAPTER 25: ACID-BASE HOMEOSTASIS AND IMBALANCES- OVERVIEW AND RESPIRATORY SYSTEM. - Define/ describe: normal serum pH range - Normal serum pH 7.4 - Normal pH range of adult blood 7.35-7.45 - High pH alkaline, Low pH acidic - Death can occur if pH falls below 6.9, pH rises above 7.8 - Normal ranges for PaCO2 and HCO3 in adults - PaCO2: 36-44 - HCO3: 22-26 - Buffers - first line of defense against pH changes in all body fluids - chemicals that help control pH of body fluids - Bicarbonate Buffer System - Most important buffer in extracellular fluid (EFC) - Keeps pH levels in the body equal throughout - When there is too much acid (acidosis) the bicarb will take up the extra hydrogen ions that are released by the acid to then become carbonic acid. Carbonic acid released as carbon dioxide through the lungs - When there is too little acid (alkaline) Bicarbonate buffer releases hydrogen ions from the weak acid to increase pH. - Role of lungs in regulating pH - lungs excrete CO2 and water from body. Lungs can excrete only carbonic acid; they cannot excrete other acids. - Lungs either put out CO2 or retain CO2 to balance pH in body. - rid the body of carbonic acid - changed in rate and depth of respiration results from stimulation of chemoreceptors that sense PaCO2 and pH of blood. - Exert an influence on and serve to alter amount of PaCO2 and carbonic acid in blood. - Bicarb chemical equation CO2 + H2O = H2CO3= HCO-3(negative) + H+(positive) - Causes of respiratory acidosis - Any condition that causes an excess of carbonic acid. - Impaired gas exchange (ex: COPD, pneumonia, severe asthma, pulmonary edema, acute respiratory distress syndrome) - Inadequate neuromuscular function (ex: guillain barre, chest injury or surgery, hypokalemic respiratory muscle weakness, severe kyphoscoliosis, respiratory muscle fatigue) - Impairment of respiratory control in the brainstem (ex: respiratory depressants drugs such as opioids/barbiturates) - Clinical Manifestations of respiratory acidosis - Headache - Tachycardia - - - Cardiac dysrhythmias Neurologic abnormalities - Blurred vision, tremors, vertigo, disorientation, lethargy, somnolence - Severe respiratory acidosis - Peripheral vasodilation with hypotension Uncompensated ABG manifestations - PaCO2 above normal - pH is below normal - Bicarb normal Compensated - Increased PaCO2 (primary imbalance) - Increased bicarb concentration (compensation) - Decreased or even normal pH, depending on degree of compensation - Respiratory Alkalosis Any condition that tends to cause a carbonic acid deficit such as, Hyperventilation - - - Clinical Manifestations - Paresthesias (numbness and tingling) of fingers and aroung mouth - Carpal and/or pedal spasm - Decreases ionized calcium, which contributes to the excitability - Increased pH of cerebrospinal and cerebral interstitial fluid alters brain cell function - Can cause confusion or excitation - Cerebral vasoconstriction Uncompensated ABG - PaCO2 to be abnormally low - pH is abnormally high - Bicarb normal Compensatory response - Renal compensation tends to return the ratio of bicarb ions to carbonic acid, moving pH toward normal - Because this takes several days and because many causes are short lived, may not be fully compensated. - Decreased PaCO2 - Decreased bicarb concenration - Increased (somewhat high) pH
