NR507 Advanced Pathophysiology MidTerm Exam (LATEST 2024/2025)

NR507 Advanced Pathophysiology MidTerm Hypersensitivity: Type 1 - ✅Type 1: Allergic reaction, Mediated by IgE, Inflammation due to mast cell degranulation Local symptoms: -itching -rash Systemic symptoms: -wheezing Most dangerous = anaphylactic reaction systemic response of hypotension, severe bronchoconstriction Main treatment: epinephrine reverses the effects Hypersensitivity: Type 2 - ✅Type 2: Cytotoxic reaction; tissue specific (ex: thyroid tissue) Macrophages are the primary effectors cells involved Can cause tissue damage or alter function Grave's disease (hyperthyroidism) - example of altering thyroid function, but does not destroy thyroid tissue Incompatible blood type- example of cell/tissue damage that occurs; severe transfusion reaction occurs and the transfused erythrocytes are destroyed by agglutination or complement-mediated lysis.

Type 1 Hypersensitivity VS. Type 2 Hypersensitivity - ✅Type 1 Hypersensitivity Organ Specific Antibody binds to the antigen on the cell surface Type 2 Hypersensitivity Not Organ Specific Antibody binds to the soluble antigen outside the cell surface that was released into the blood or body fluids, and the complex is then deposited in the tissues Hypersensitivity: Type 3 - Examples - ✅Rheumatoid arthritis: Antigen/antibodies are deposited in the joints Systemic Lupus Erythematosus (SLE)- very closely related to autoimmunityantigen/antibodies deposit in organs that cause tissue damage Hypersensitivity: Type 4 - ✅Delayed response

Does not involve antigen/antibody complexes like Types 1, 2 and 3 Is T-cell mediated Differentiating Between the Rash of a Type 1 vs. Type 4 Reaction: - ✅Type 1: Immediate hypersensitivity reactions, termed atopic dermatitis, are usually characterized by widely distributed lesions Type 4: Contact dermatitis (delayed hypersensitivity) consists of lesions only at the site of contact with the allergen The key determinant is the timing of the rash: -Type 1 = Immediate -Type 4 = Delayed: Several days following contact, ex would be poison ivy Treatment of Type 4 Rash - ✅A non-severe case of contact dermatitis would be treated with topical corticosteroid.

Why not epinephrine or antihistamines?

-Epinephrine is for emergent Type 1 anaphylactic reactions. Antihistamines act on the H1 receptors. Type 4 does not involve mast cells and H1 receptors.

Antibiotics not appropriate since not an infection Autoimmunity - ✅Autoimmune disease can be familial, Affected family members may not all develop the same disease, but several members may have different disorders characterized by a variety of hypersensitivity reactions, These include autoimmune and allergic reactions Associations with particular autoimmune diseases have been identified for a variety of major histocompatibility complex (MHC) alleles or non-MHC genes Alloimmunity - ✅General term used to describe when an individual's immune system reacts against antigens on the tissues of other members of the same species.

Examples: Neonatal disease where the maternal immune system becomes sensitized against antigens expressed by the fetus, Transplant rejection, Transfusion reaction Primary Immunodeficiency - ✅Most primary immune deficiencies are result of single gene defects Something is lacking with the immune system itself.

Example: B-lymphocyte deficiency - one of the most severe forms of a primary immunodeficiency

Secondary Immunodeficiency - ✅Complication of some other physiological condition/disease, Malnutrition one of most common causes worldwide. Example: Pt. with HIV gets pneumocystis carinii Hematology - ✅Anemias, Involve RBCs, Most of body's iron stores come from the recycling of iron from old RBCs Iron Deficiency Anemia - ✅Microcytic/Hypochromic Anemia, Caused by disorders of hemoglobin synthesis, particularly iron deficiency, Ferritin is an important measurement that reflects the body's total iron stores, The NP will order a ferritin level to get an idea of the body's total iron stores, Low ferritin reflects anemia Major Lab Marker for Anemia - ✅Increased RBC distribution width (RDW) is one of the earliest lab markers in developing microcytic or macrocytic anemia Folate Deficiency - ✅Can cause megaloblastic anemia, Alcoholics can easily get folate deficiency Ferritin level normal Hgb low Hct low Vitamin B-12 Deficiency - ✅Fatigue, Dyspnea, Peripheral Neuropathy in BLE (numbness and tingling) Risk Factors: Older adults, H-pylori infection Affects Vitamin B-12 absorption Hemolytic Anemia - ✅Who is at risk?

RBCs destroyed, Mismatched blood types destroy RBCs. Autoimmune hemolytic anemia due to autoantibodies against erythrocytes that the immune system perceives as an antigen and then attacks it. Allergic reaction to a drug causes drug-induced hemolytic anemia Acute Blood Loss Anemia - ✅Trauma victims who are losing blood, GI bleed (Acute) Aplastic Anemia - ✅Diagnosis made by blood tests and bone marrow biopsy.

AA is suspected if levels of circulating erythrocytes, leukocytes and platelets diminished: -Granulocyte count less than 500/ uL -Platelet count less than 20,000/ uL -Absolute reticulocyte count less than or equal to 40 x 109/ L

Sickle Cell Anemia - ✅Patients encountered who have sickle cell trait, Inherited a normal Hb gene from one parent and an abnormal Hb gene from the other parent Thalassemia - ✅Inherited blood disorder causing decreased circulating hemoglobin, Many possible genetic mutations Heart Failure - ✅Pathophysiology (Wk 2 Discussion) Underlying patho is that there is less cardiac output to meet the body's oxygen demands.

Over time there is decreased contractility, decreased stroke volume, increased left ventricular end-diastolic volume (LVEDV) When contractility is decreased, stroke volume falls, and LVEDV increases. This causes dilation of the heart and an increase in preload.

Major risk factor is long standing hypertension. Preload = stretch Afterload = resistance Differentiate between Right and Left Heart Failure - ✅Sometimes right-sided heart failure can occur due to left-sided heart failure due to the back up of fluid from the left side to the right.

Sometimes right-sided heart failure can occur without there being left-sided heart failure; this usually occurs because the person has long standing pulmonary issues (COPD).

Patients will have classic R. sided heart failure symptoms without L. sided heart failure symptoms: Right JVD distention, Peripheral edema, Hepatosplenomegaly Stages of Heart Failure (ACC/AHA) - ✅-Stage A: patient has risk factors (CAD) but no symptoms; no structural heart damage -Stage B: patient has structural heart damage (MI), but still has no symptoms -Stage C: patient is symptomatic with alteration in their daily functions due to dyspnea, swelling, etc. This is where the NYHA functional classifications come into play -Stage D: end-stage heart-failure - have maximized medications to treat it. May need heart transplant or pacemaker NYHA Functional Classifications- It's all about the impact on the patient's activity caused by the HF symptoms: - ✅-Stage I: Mild- no limitation of physical activity; Ordinary physical activity does not cause symptoms -Stage II: Mild- slight limitation of physical activity; comfortable at rest; Ordinary physical activity results in fatigue, palpitation, dyspnea or anginal pain.

-Stage III: Moderate- marked decrease in physical activity; marked limitation of physical activity; comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea or anginal pain. -Stage IV: Severe- inability to carry on any physical activity without discomfort. Symptoms of HF or the anginal syndrome may be present even at rest. If any physical activity undertaken, discomfort is increased.

Heart Valve Disorders - ✅Signs and Symptoms (Edapt Scenarios), Murmur Characteristics, Important to know Anatomy

Aortic Stenosis - ✅Blood backed up into left ventricle causing perfusion problems for the rest of the body Causes: Bicuspid aortic valve- congenital condition (only two cusps to the aortic valve which usually has three cusps)- the two cusps get damaged quicker because they are doing the work of three Age related calcification- obstruction/ stenosis Smoking, High BP, Hypertension, Hyperlipid, Diabetes Rheumatic Fever Signs & Symptoms = SAD S: Syncope A: Angina D: Dyspnea **Fainting Chest pressure upon exercising Sustained, laterally displaced apical pulse Mid-systolic crescendo-decrescendo murmur heard loudest at base and radiating to the neck S4 gallop present** Aortic Regurgitation - ✅Blood is coming back from the Aorta into the L. Ventricle through the Aortic Valve Causes Widening or aneurysmal change of the aortic annulus (ring of fibrous tissue surrounding the aorta) Endocarditis Rheumatic Fever Signs & Symptoms Fatigue Syncope SOB Palpitations Widened Pulse Pressure L. Ventricular Dilation Early diastolic murmur along left sternal border **Shortness of breath that progressively worsens High pitched early diastolic murmur heard loudest at left lower sternal border Diastolic rumbling sound at the heart's apex Systolic crescendo-decrescendo murmur heard at the left upper sternal border

A chest x-ray may show signs of pulmonary edema and cardiomegaly** Mitral Stenosis - ✅Blood is going to back up into the L. Atrium and Lungs Causes Rheumatic Fever / Rheumatic Heart Disease Endocarditis Signs & Symptoms Fatigue SOB Exercise intolerance Cough L. Atrial enlargement Pulmonary congestion/edema Diastolic rumble Opening snap before Diastolic rumble **As mitral stenosis progresses, symptoms of decreased CO occur, especially during exertion Shortness of breath on activity Pounding/racing heart Associated w/ history of Rheumatic HD A low-pitched murmur auscultated at the heart's apex JVD and bilateral crackles in lung bases noted ECG demonstrates A-FIB and Left Ventricular Hypertrophy** Mitral Regurgitation - ✅Blood goes from L. Ventricle to L. Atrium and then to the Lungs Causes - Anything that causes LV dilation Remodeling process (post MI) Dilated cardiomyopthathy Rheumatic Fever/ Rheumatic Heart Disease Endocarditis Papillary muscle dysfunction/rupture/ chordae tendinae Calcification of the valve/around the valve Signs & Symptoms Acute Chronic **Shortness of breath JVD, Crackles in bilateral lung bases Blowing pansystolic murmur heard best at heart's apex and radiates to back and axilla** Obstructive vs. Restrictive Pulmonary Disease - ✅Obstructive: decreased FEV1 indicates airway obstruction along with low FEV1/FEV ratio 56%

Restrictive: FEV1/FVC ratio above 70%, Review EDapt examples Asthma - ✅Airways constricted Intrinsic: triggered by something internal such as anxiety Extrinsic: triggered by something in outside environment- something in the air (dust mites/pet dander) In mildest form of asthma (intermittent), short acting beta2-agonist inhalers are prescribed Mild-persistent asthma will have night symptoms 3-4 days a month COPD - ✅Diagnosis based on Hx of symptoms, physical exam, chest imaging, pulmonary function tests and blood gas analysis Pulmonary function testing reveals airway obstruction (decreased FEV1) that is progressive and unresponsive to bronchodilators, Emphysema, Chronic bronchitis COPD Staging According to GOLD Guidelines- Based on degree of airway limitation ✅Gold 1: Mild: FEV1≥80% predicted Gold 2: Moderate: 50% ≤FEV1 <80% predicted Gold 3: Severe: 30% ≤FEV1 <50% predicted Gold 4: Very Severe: FEV < 30% predicted Emphysema - ✅Damage occurs in the alveoli, Impairs gas exchange, Issue is in expiration- they can get air in but cannot get air out Air trapping, Pursed lip-breathing Increased A&P diameter, Barrel chest Chronic Bronchitis - ✅Productive cough with copious amounts of sputum dyspnea wheezing rhonchi and cyanosis of the skin and mucous membranes Damage occurs in the airway- not the alveoli, Mucous Plugs Forced Vital Capacity (FVC) - ✅Normal 80-120% The FVC measures the volume of air in the lungs that can be exhaled.

Patient inhales as deep as possible and then exhales as long and as forcefully as possible.

Obstructive: Will be decreased or normal Restrictive: Will be decreased

Forced Expiratory Volume in 1 second (FEV1) - ✅Normal 80-120% Amount of air forcefully exhaled from the lungs in the first second.

The patient inhales and forcefully exhales as fast as possible.

Obstructive: Will be decreased Restrictive: Will be decreased FEV1/FVC ratio - ✅Determines if the pattern is obstructive, restrictive or normal Normal is 70% or less than the lower limit of normal for the patient This is a calculated ratio that represents the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration to the full, forced vital capacity.

Obstructive: Less than 70% Restrictive: Normal or > 70% Diffusing capacity - ✅The diffusing capacity is simply how well the lungs are able to exchange gas Residual volume (RV) - ✅RV is the amount of air that remains in the lungs after a forceful exhalation Total Lung Capacity (TLC) - ✅RV + FVC = TLC Normal range is 80-120% of predicted Obstructive: >120% (represents hyperinflation) Restrictive: <80% Microcytic anemia - ✅(MCV<80 fL) describes RBCs that are small.

Iron deficiency Sideroblastic Thalassemia Anemia of chronic disease Macrocytic anemia - ✅(MCV>100 fL) describes RBCs that are large.

B12 deficiency (pernicious anemia) Folate deficiency

Normocytic anemia - ✅(MCV 80-99 fL) describes RBCs that are normal in size.

Anemia of inflammation and chronic disease Hereditary spherocytosis G6PD deficiency Paroxysmal nocturnal hemoglobinuria Hypochromic anemia - ✅RBCs with less hemoglobin than normal. As a result, the RBCs appear pale in color (MCHC is low).

Hyperchromic anemia - ✅RBCs with more hemoglobin than normal. As a result, the RBCs appear a dark hue or red than normal cells (MCHC is high).

Normochromic anemia - ✅RBCs that have a normal amount of hemoglobin. As a result, the RBCs appear neither pale nor dark (MCHC is normal).

Decreased tissue oxygenation from anemia can manifest as signs and symptoms of the following: - ✅Severe fatigue Pallor Weakness Dyspnea Dizziness Cardiac Output (CO) - ✅The amount of blood that the heart pumps in 1 minute. CO is also known as cardiac contractility.

CO=heart rate (HR) x stroke volume (SV).

Stroke Volume (SV) - ✅The volume of blood pumped out of the left ventricle during each systolic cardiac contraction.

Afterload - ✅The force, or load, which the heart must contract against in order to pump blood.

Afterload is also known as systemic vascular resistance (SVR).

Preload - ✅The amount of stretch that the cardiac muscle exhibits at the end of ventricular filling.

Right-sided Heart Failure - ✅S/Sx: Jugular vein distention Hepatosplenomegaly Peripheral edema CorPulmonale

Tricuspid valve damage Right ventricle superior vena cava (preload) pulmonary artery (afterload) Causes of right heart failure include: 1) pulmonary disease that causes pulmonary hypertension. This is the most common cause; 2) right ventricular myocardial infarction (MI), which weakens the cardiac muscle; 3) right ventricular hypertrophy (secondary to cardiac damage); 4) tricuspid valve damage (causing backflow of the blood into the right atrium or right ventricle after ejection); 5) secondary failure as a result of left heart failure due to the build-up of pressure in the damage left ventricle Left-Sided Heart Failure - ✅S/Sx: Increased left ventricular afterload Decreased ejection fraction Increased left ventricular preload Pulmonary edema Dyspnea Left ventricle Pulmonary vein (preload) Aorta (afterload) This increased pressure will force fluid from the pulmonary capillaries into the pulmonary tissues, which essentially floods those areas. The result is pulmonary edema and dyspnea. If left ventricular heart failure is unresolved, volume and pressure will continue to build until it reaches the right side of the heart, contributing to right heart failure as well