Exam 4 Worksheet PDF

Exam 4 Worksheet For each disease or condition listed, consider the following questions: 12 1213 1. What are the hallmark clinical signs and symptoms? 2. What are the primary pathophysiologic mechanisms? 3. What diagnostic tools and results are used to confirm...

Exam 4 Worksheet For each disease or condition listed, consider the following questions: 12 1213 1. What are the hallmark clinical signs and symptoms? 2. What are the primary pathophysiologic mechanisms? 3. What diagnostic tools and results are used to confirm the diagnosis? 4. What are the complications or secondary conditions associated with it? 5. How do patient-specific factors (age, lifestyle, comorbidities) affect risk or management? For each condition, ensure you can explain how the symptoms relate to the underlying pathophysiology and what makes each disease process unique compared to others with similar presentations. Understanding these relationships will help you answer both straightforward and nuanced questions on the exam. CARDS 1. Cardiac Tamponade (minimal book and PP info but we all know this one pretty well) - Primary Patho: - When fluid accumulation in the pericardial sac is large/sudden it can lead to external compression of the heart chambers such that impairs filling. - Risk Factors: - Hypertension, aortic dissection, pericardial effusion. - Hallmark s/s: - Beck’s Triad: Hypotension, distended neck veins and muffled heart sounds. Pulsus Paradoxus (abnormal decrease in SBP with each inspiration) Decreased stroke volume, compensatory increased HR - Diagnostics: - Echo and s/s - Complications/Secondary Conditions: - if untreated, death 2. Atherosclerosis/CAD - Primary Patho: (watch some videos, this is a lot) - Formation of atherosclerotic plaque is initiated by injury to coronary artery endothelium. Causing permeability and leukocytes recruitment. LDL accumulation occurs with oxidation by endothelial cells and macrophages. Oxidized lipids are damaging to endothelial and smooth muscle cells, and stimulate recruitment of macrophages into the vessel. Macrophages engulf the lipids.Causing foam cells. Foam cells rupture and release their contents and those are engulfed by more causing increased plaque growth. Excess lipid and debris accumulate forming the lipid core within the vessel wall. Vulnerable plaque are likely due to large lipid core, thin cap and high shear stress increasing rupture likelihood. - Lesions called atheromas (atheromatous or atherosclerotic plaques)that protrude into vessel lumens. - Atheromatous plaque typically consists of a raised lesion with a soft core of lipid (SEE PIC). They mechanically obstruct blood flow but can also rupture and lead to vascular thrombosis. Due to creating distance between the lumin and media, can cause weakening of the vascular wall and aneurysm formation. - Endothelial injury and dysfunction- causes increased vascular permeability, leukocyte adhesion, and thrombosis. EC (endothelial cell) injury is the cornerstone of the “response-to-injury” hypothesis. - Early lesions begin at sites of intact endothelium that exhibit features of endothelial dysfunction which are increased permeability, enhanced leukocyte adhesion, and altered gene expression. - Causes of EC dysfunction include toxins from cigarette smoke, homocysteine, and the local production of inflammatory cytokines. Three most important causes of endothelial dysfunction are hemodynamic disturbances, hypercholesterolemia, and inflammation. - Risk Factors: - Family history is the most important independent risk factor.  - (Nonmodifiable) genetic abnormalities (familial hypercholesterolemia), family history, increasing age, male gender, - (Modifiable) Hyperlipidemia, increased LDL, HTN. smoking, DM, inflammation. - Hyperhomocysteinemia associated with risk prediction. - Lipoprotein a [Lp(a)] is an altered form of LDL that contains the apolipoprotein B-100 portion of LDL linked to apolipoprotein A (apo A); Lp(a) levels are associated with coronary and cerebrovascular disease risk, independent of total cholesterol or LDL levels. - Hallmark s/s: - stenosis, ischemic injury, chest pain with exertion due to 70-7% decrease in luminal cross-sectional area. Thrombus formation. - Diagnostics: - CRP is an acute phase reactant synthesized primarily by the liver. Now being used for dx risk. LDL levels, Lp(a) levels, genetic testing. - Complications/Secondary Conditions: - Increases risk of MI 5 fold (ages 40-60). CVA, Aortic aneurysm, PVD. See pics for plaque progression and outcomes. - Hypercholesterolemia: (not a subsection but directly related to CAD/athero so adding it separately) - Patho: Lipids are transported in the bloodstream through specific apoproteins. Dyslipoproteinemias are lipoprotein abnormalities in the general population. - Increased LDL, decreased HDL, increased levels of abnormal Lp(a) - Risk factors: resulting from mutations in apoproteins or lipoprotein receptors due to nephrotic syndromes, alcoholism, hypothyroidism or DM. - Hallmark: - Dx: - Complications: leads to atherosclerosis, the dominant lipids in plaque is cholesterol and cholesterol esters. 3. Ischemic Heart Disease - Primary Patho: - an imbalance between myocardial supply (perfusion) and cardiac demand for oxygenated blood - Risk Factors: - insufficient coronary perfusion relative to myocardial demand due to  - Large, stable atherosclerotic plaque. - Acute platelet aggregation and thrombosis. - Vasospasm. - Failure of autoregulation by the microcirculation - Poor perfusion pressure - Hallmark s/s: - Angina - Diagnostics: - EKG, Stress Test, ECHO - Complications/Secondary Conditions: - Myocardial infarction (MI), in which ischemia causes frank cardiac necrosis. - Angina pectoris (literally “chest pain”), in which ischemia is not severe enough to cause infarction, but the symptoms nevertheless portend infarction risk. (see point 11) - Chronic IHD with heart failure - Sudden cardiac death (SCD) Myocardial Infarction - Primary Patho: - An atheromatous plaque is eroded or suddenly disrupted by endothelial injury, intraplaque hemorrhage, or mechanical forces, exposing subendothelial collagen and necrotic plaque contents to the blood. - Platelets adhere, aggregate, and are activated, releasing thromboxane A2, adenosine diphosphate (ADP), and serotonin—causing further platelet aggregation and vasospasm. - Activation of coagulation by tissue factor and other mechanisms adds to the growing thrombus. - Within minutes, the thrombus can evolve to completely occlude the coronary artery lumen. - Risk Factors: - In more than 90% of cases, MI results from reduced blood flow due to obstructive atherosclerotic lesions in the epicardial coronary arteries; consequently, IHD is frequently referred to as coronary artery disease (CAD). - Hallmark s/s: - Changes on EKG (ST Elevation), Angina - Diagnostics: - Biomarkers of myocardial damage are cardiac-specific troponins T and I (cTnT and cTnI), proteins that normally regulate calcium-mediated contraction of cardiac muscle - Cardiac troponins begin to rise in 2 to 4 hours and peak at 24 to 48 hours after an acute infarct. With reperfusion, troponin levels may be higher and peak earlier owing to more rapid washout of the marker from the necrotic tissue. - Complications/Secondary Conditions: - Profuse sweating (diaphoresis), and nausea and vomiting are common and can suggest involvement of the posterior-inferior ventricle with secondary vagal stimulation. - Dyspnea due to impaired contractility of the ischemic myocardium and the resultant pulmonary congestion and edema is a frequent symptom. - MI leads to drop in CO, triggering compensatory responses including sympathetic activation - Sympathetic nervous system activation leads to increased myocardial workload by increasing: Heart rate, Contractility, Blood pressure, and Chest pain (usually more severe and lasts longer) - more than 30 minutes chest pain described as crushing, stabbing, or squeezing, associated with a rapid, weak pulse. 4. Rheumatic heart disease - Primary Patho: - Acute inflammatory disease that follows infection with group A β-hemolytic streptococci (strep-throat and glomerulonephritis). Antibodies against the streptococcal antigens damage connective tissue in joints, heart, and skin - Risk Factors: - Exposure to strep A and the development of rheumatic fever - Hallmark s/s: - Fever; sore throat; joint inflammation; involuntary movements (Sydenham chorea); and a distinctive truncal rash. - Diagnostics:  - clinical manifestations after years of delay post rheumatic fever - Complications/Secondary Conditions: - RHD is characterized principally by deforming fibrotic valvular disease, particularly involving the mitral valve. RHD is virtually the only cause of mitral stenosis. 5. Aortic Regurgitation vs Stenosis - Stenosis is the failure of a valve to open completely, obstructing forward flow. Acquired valvular stenosis is almost always due to a primary leaflet abnormality and is virtually always a chronic process. - Insufficiency results from failure of a valve to close completely, thereby allowing regurgitation (backflow) of blood. Valvular insufficiency can result from either intrinsic disease of the valve leaflets (e.g., endocarditis) or disruption of the supporting structures without primary leaflet injury. 6. Thrombus formation - Primary Patho: - Stasis or turbulence: - Promote endothelial activation, enhancing procoagulant activity and leukocyte adhesion, in part through flow-induced changes in the expression of adhesion molecules and pro-inflammatory factors - Disrupt laminar flow and bring platelets into contact with the endothelium - Prevent washout and dilution of activated clotting factors by fresh flowing blood and the inflow of clotting factor inhibitors - Hypercoagulability: - Either primary (e.g., factor V Leiden, increased prothrombin synthesis, antithrombin III deficiency) or secondary (e.g., bed rest, tissue damage, malignancy, or development of aPL antibodies [antiphospholipid antibody syndrome]) or antibodies against PF4/heparin complexes [heparin-induced thrombocytopenia]) - Thrombi may propagate, resolve, become organized, or embolize. - Thrombosis causes tissue injury by local vascular occlusion or by distal embolization. - Risk Factors: - Primary abnormalities that lead to thrombosis are the so-called Virchow triad: - (1) endothelial injury: by toxins, hypertension, inflammation, or metabolic products and is associated with endothelial activation and changes in endothelial gene expression that favor coagulation which leads to platelet activation. - (2) stasis or turbulent blood flow: Underling thrombus formation in the heart and the arterial circulation, where the high rate of blood flow impedes clot formation. - (3) hypercoagulability of the blood: Cardiac and arterial clots are typically rich in platelets, and it is believed that platelet adherence and activation is a prerequisite for thrombus formation under high shear stress, such as exists in arteries - Decreased blood flow in the setting of prolonged immobilization is the most common cause of lower extremity deep venous thrombosis (DVT); account for more than 90% of cases - Hallmark s/s:  - Depending on location of thrombus. Migratory thrombophlebitis (Trousseau syndrome) appears in one location then disappears to another. - local manifestations including vein dilation, edema, cyanosis, heat, erythema, or pain may be entirely absent, especially in bedridden patients - pain can be elicited by pressure over affected veins, squeezing the calf muscles, or forced dorsiflexion of the foot (Homan sign); - Diagnostics: - US of lower extremities - Complications/Secondary Conditions: - Pulmonary Emboli, CVA, MI 7. RAAS system (watch videos on this) - Primary Patho: - Renin is a proteolytic enzyme produced by renal juxtaglomerular cells, adjacent to the glomerular afferent arterioles. - Renin is released in response to ↓ blood pressure in afferent arterioles, elevated levels of circulating catecholamines, or low sodium levels in the distal convoluted renal tubules. - When the glomerular filtration rate falls (e.g., when the cardiac output is low) renin is released, leading to ↑ sodium reabsorption by the proximal tubules. - Renin cleaves plasma angiotensinogen to angiotensin I, its converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II ↑ blood pressure by - (1) inducing vascular contraction - (2) stimulating aldosterone secretion by the adrenal gland - (3) ↑ tubular sodium resorption. - Adrenal aldosterone ↑ sodium resorption (and thus water) in the distal convoluted tubules, which ↑ blood volume. - The kidney produces a variety of vascular relaxing substances ( prostaglandins and NO) that counterbalance the vasopressor effects of angiotensin. - Myocardial natriuretic peptides are released from atrial(major) and ventricular (minor) myocardium d/t volume expansion; inhibiting sodium resorption in the distal renal tubules, causing sodium excretion and diuresis. Inducing systemic vasodilation. - Long term regulation of BP: - (RAAS) important regulator of BP - Increase in extracellular fluid volume = ↑CO and SVR = ↑BP - Causes kidneys to excrete excess sodium and fluid - Sodium ↑ the osmolality of the ECF - ↑ osmolality causes the release of (antidiuretic hormone) ADH secretion - Causes kidneys to reabsorb water and sodium - Angiotensin II produces an ↑ in SVR - Atrial natriuretic peptides cause kidneys to ↑ sodium and water excretion by ↑ the glomerular filtration rate - Intrarenal arteriolar constriction leads to ↑ tubular reabsorption of sodium and water 8. Types of shock excluding anaphylactic 9. Myocarditis - Primary Patho: Inflammatory disorder of the heart muscle characterized by necrosis and degeneration of myocytes  - Risk Factors: - Hallmark s/s: fatigue, dyspnea, palpitations, precordial discomfort, and fever. The clinical features of myocarditis can mimic those of acute MI - Diagnostics: Myocarditis, or inflammation of the heart muscle, can be difficult to diagnose because of its nonspecific symptoms. EKG, ECHO, chest x-ray, MRI - Complications/Secondary Conditions: Myocarditis can interfere with heart function, and the heart muscle can be permanently damaged. Scar tissue may form as a result of the inflammation and interfere with heart function, plus increase the risk for abnormal heart rhythms. However, myocarditis doesn't always cause permanent damage to the heart 10. Mitral Valve Stenosis vs Prolapse - mitral stenosis – the valve does not open as wide as it should. mitral regurgitation – the valve leaks and blood flows the wrong way. mitral valve prolapse – the valve becomes too floppy. 11. Angina - Primary Patho: Angina occurs when the heart muscle doesn't receive enough oxygen, a condition called ischemia. This is usually caused by an imbalance between the heart's oxygen demand and supply - Risk Factors: smoking, lack of physical activity, stress, alcohol, HTN, DM, high cholesterol, obesity, family hx  - Hallmark s/s: chest pain or discomfort that can feel like pressure, tightness, squeezing, burning, or heaviness: - Diagnostics: EKG, chest x-ray, cardiac enzymes, stress test, ECHO - Complications/Secondary Conditions: unstable/stable angina, MI, sudden cardiac death 12. Giant Cell arteritis - chronic, classically granulomatous inflammation of large- to small-sized arteries that principally affects arteries in the head - Primary Patho: occurs when the body's immune system abnormally attacks the walls of medium- and large-sized arteries. likely occurs as a result of a T cell–mediated immune response to a vessel wall antigen. ​ - Proinflammatory cytokines (especially TNF) and anti-EC antibodies also contribute. ​ - Risk Factors: those over 50, women are twice as likely, those of northern european descent, family history - Hallmark s/s: severe persistent headaches, scalp tenderness, jaw pain, vision problems, flu-like symptoms - Diagnostics: temporal artery biopsy, CT, MRI, PET scan, lab testing (CRP) - Complications/Secondary Conditions: vision loss, aortic aneurysm, stroke, peripheral arterial complications, TIAs 13. Cardiomyopathy Primary cardiomyopathies involve predominantly the heart. They may be genetic or acquired (e.g., viral myocarditis, anthracycline cardiotoxic).​ Secondary cardiomyopathies have myocardial involvement as a component of a systemic or multiorgan disorder​ ​ Classified by cause or functional impairment​ ​ Functional classifications ​ Dilated​ Hypertrophic​ Restrictive  14. Differentiate types of arrhythmias and the mechanisms behind their development Sick sinus syndrome. If the SA node is damaged, other fibers or even the AV node can take over pacemaker function, albeit at a much slower intrinsic rate (causing bradycardia).​ Atrial fibrillation. If the atrial myocytes become “irritable” and depolarize independently and sporadically (as occurs with atrial dilation), the signals are variably transmitted through the AV node, leading to the random “irregularly irregular” heart rate.​ Heart block. If the AV node is dysfunctional, varying degrees of heart block occur, ranging from simple prolongation of the P-R interval on electrocardiogram (first-degree heart block), to intermittent transmission of the signal (second-degree heart block), to complete failure (third-degree heart block).​ Genetic and heritable conditions play a role in disease development in some patients​ 15. Conduction disturbances CONDUCTION PATHWAY DISTURBANCES Include delays, blocks, and abnormal pathways Conduction blocks and delays commonly associated with cardiac ischemia and infarction Abnormal pathways are usually congenital Alternative pathways for depolarization result in abnormally early ventricular depolarization following atrial depolarizations Wolff-Parkinson-White syndrome Atrioventricular Conduction Disturbances Intraventricular Conduction Defects Disturbance in conduction between sinus impulse & associated ventricular Bundle branch block - abnormal conduction response of impulses through the interventricular bundle branches 1st Degree Block - prolongation of the P-R interval No treatment required Right bundle branch supplies right ventricle 2nd Degree Block (types I and II) - intermittent transmission of the signal Type I (Wenckeback, Mobitz type I) - progressive prolongation of PR Left bundle branch supplies left ventricle interval until one P waves is not conducted (further divided into anterior, posterior, and ○ AV nodal ischemia septal) Type II - consistent PR interval with some non conducted P waves ○ More serious because can progress to complete AV block (3rd degree) 3rd Degree Block- complete failure No association between atrial and ventricular conduction - more serious ○ Lead to slow ventricular rhythm and poor CO 16. Heart Failure- Differentiate Right vs Left - Patho: Heart cannot pump blood to adequately meet the metabolic demands of peripheral tissues or can do so only at elevated filling pressures. - Characterized by variable degrees of decreased cardiac output and tissue perfusion (forward failure), as well as pooling of blood in the venous capacitance system (backward failure); the latter may cause pulmonary edema, peripheral edema, or both  Right Sided HF Left Sided HF Usually caused by left-sided heart failure, as increased pressure in the Pulmonary congestion​ pulmonary circulation puts strain on the right side of the heart. Edema​ Dyspnea, dyspnea on exertion, orthopnea and paroxysmal Causes of right-sided heart failure include all the causes of left-sided heart nocturnal dyspnea​ failure. Cough, respiratory crackles (rales), hypoxemia, and high Isolated right-sided heart failure (rare) typically results from lung left-atrial pressure, cyanosis​ disorders, known as cor pulmonale. Cardiomegaly, tachycardia, S3, S4, MVR, afib​ Pathway: Pulmonary disorders → increased vascular resistance → high Respiratory symptoms in heart failure include fine rales at the lung afterload → right ventricular hypertrophy (cor pulmonale) → right bases, caused by edematous alveoli snapping open during inspiration. ventricular failure. Other signs of left ventricular failure: Backward effects: Systemic venous congestion leads to edema, ascites, jugular vein distension, impaired mental function, hepatomegaly, and splenomegaly. Enlarged heart (cardiomegaly) on imaging. Tachycardia. Hepatojugular reflux test is used for diagnosis. A third heart sound (S3) from volume overload or a Forward effects: Decreased output to the left ventricle, leading to low fourth heart sound (S4) from increased myocardial cardiac output (CO). stiffness. Right-sided heart failure causes more renal congestion than left-sided, leading to fluid retention, peripheral edema, and more severe azotemia. Progressive ventricular dilation can lead to mitral regurgitation as the papillary muscles are displaced. Venous congestion and hypoxia in the central nervous system can impair mental function, similar to left-sided heart failure. Chronic left atrial dilation may cause atrial fibrillation, reducing the atrial contribution to ventricular filling, which decreases stroke Right-sided heart failure significantly affects the kidney and the brain. volume. 17. Aneurysm - Patho: - Aneurysm: A localized abnormal dilation of a blood vessel or the heart, either congenital or acquired. - True aneurysm: Involves all the layers of an intact but weakened arterial or ventricular wall (e.g., atherosclerotic, congenital vascular aneurysms, or those post-myocardial infarction). - False aneurysm (pseudoaneurysm): A defect in the vessel wall leads to a hematoma that communicates with the intravascular space. - Dissection: Blood enters the vessel wall, separating its layers, and can result from a tear or rupture of the vasa vasorum. - Risk Factors: - Atherosclerosis,Congenital conditions, Transmural myocardial infarctions (for ventricular aneurysms) - Hallmark s/s: - Saccular aneurysms: Spherical outpouching of a portion of the vessel wall; commonly 2 to 20 mm in intracranial vessels and 5 to 10 cm in the aorta. - Fusiform aneurysms: Diffuse, circumferential dilation of a long segment of a vessel, often 5 to 10 cm in the aorta and involving the aortic arch, abdominal aorta, or iliac arteries. - Diagnostics: - Complications/Secondary Conditions: Rupture of true or false aneurysms or dissections, often with catastrophic outcomes. Thrombosis in aneurysms, particularly in fusiform types. 18. Hypertension - Patho: - Hypertension can occasionally be caused by single-gene disorders or can be secondary to diseases of the kidney, adrenal glands, or other endocrine organs. - Sustained hypertension requires the participation of the kidney, which normally responds by eliminating salt and water. - In established hypertension, both increased blood volume and increased peripheral resistance contribute to the elevated blood pressure. - Histologically, hypertension causes thickening of arterial walls due to hyaline deposits and, in severe cases, by the proliferation of endothelial cells (ECs) or smooth muscle cells (SMCs) and basement membrane replication. - Risk Factors: single-gene disorders and secondary conditions affecting the kidney and endocrine system - Hallmark s/s: - ​Hypertension is typically asymptomatic until late in its course. - Malignant hypertension (5% of cases): Rapidly rising blood pressure (SBP > 200 mm Hg, DBP > 120 mm Hg), often leading to renal failure, retinal hemorrhages, exudates, and possibly papilledema. - Hypertensive emergency: A sudden, severe increase in BP with end-organ damage (e.g., renal failure, retinal changes, cardiovascular events). - Hypertensive urgency: Similar BP elevation but without end-organ damage. - Diagnostics: - Monitor for severe pressure elevations and assess for signs of end-organ damage (renal failure, retinal hemorrhages, cardiovascular complications). - Parenteral antihypertensive agents are used in hypertensive emergencies, requiring ICU monitoring.  - In hypertensive urgency, oral medications are used to reduce BP over 24-48 hours. - Complications/Secondary Conditions: end organ damage - Renal failure, stroke, and heart disease. - Cardiovascular disease from atherosclerosis - Heart failure due to increased myocardial workload. - Kidney failure from glomerular damage. - Affects the microcirculation of the eyes, possibly causing retinal hemorrhages and exudates. - Increased pressure in cerebral vasculature can lead to hemorrhage. Essential Hypertension Secondary Hypertension Insufficient renal sodium excretion at normal arterial pressure may Renovascular hypertension: Renal artery stenosis decreases initiate essential hypertension. glomerular flow and pressure, leading to increased BP. Results in increased fluid volume, cardiac output, and peripheral Primary hyperaldosteronism: Common cause of secondary vasoconstriction, raising blood pressure. hypertension, either idiopathic or caused by aldosterone-secreting adrenal adenomas. Kidneys excrete enough sodium to balance intake at a higher BP (resetting of pressure natriuresis). Single-gene disorders: Rare, severe forms of hypertension due to gene defects affecting aldosterone metabolism or sodium reabsorption (e.g., Vasoconstriction increases peripheral resistance, contributing to Liddle syndrome). essential hypertension. Pheochromocytoma: Environmental factors involved in hypertension: Tumors of chromaffin cells that release catecholamines (and Stress sometimes peptide hormones), causing hypertension. Obesity 90% of patients exhibit hypertension; two-thirds have paroxysmal episodes with abrupt BP spikes, tachycardia, palpitations, Smoking headaches, sweating, and tremor. Physical inactivity Triggers for episodes: stress, exercise, posture changes, tumor High salt consumption. palpation, micturition (urinary bladder paragangliomas). Can lead to cardiac complications like congestive heart failure, pulmonary edema, myocardial infarction, and ventricular arrhythmias due to catecholamine toxicity. Lab diagnosis: Increased urinary excretion of catecholamines and metabolites (e.g., vanillylmandelic acid, metanephrines). Treatment: Surgical excision with adrenergic-blocking agents; multifocal lesions require long-term medication for hypertension. 19. Mechanics behind BP and HR regulation Blood Pressure Regulation Blood Pressure (BP) = Cardiac Output (CO) × Peripheral Vascular Resistance (PVR). Cardiac Output: ○ CO = Stroke Volume (SV) × Heart Rate (HR). ○ SV is primarily determined by filling pressure, regulated by sodium homeostasis and blood volume. ○ HR and myocardial contractility are influenced by the α- and β-adrenergic systems affecting vascular tone. Peripheral Resistance: ○ Regulated mainly at the arterioles through neural and hormonal inputs. ○ Vascular tone is a balance between vasoconstrictors (e.g., angiotensin II, catecholamines, endothelin) and vasodilators (e.g., kinins, prostaglandins, nitric oxide). BP is fine-tuned by tissue pH and hypoxia to meet local metabolic needs. Renin-Angiotensin-Aldosterone System (RAAS) Renin: Secreted by kidneys in response to low blood pressure, low sodium, or elevated catecholamines. ○ Converts angiotensinogen to angiotensin I, which is converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II: ○ Increases BP by inducing vascular contraction, stimulating aldosterone secretion, and enhancing tubular sodium resorption. Aldosterone: ○ Increases sodium and water resorption in the distal convoluted tubules, elevating blood volume and BP. Vascular Relaxing Substances: Kidneys also produce substances (e.g., prostaglandins, nitric oxide) to counterbalance vasopressor effects. Atrial Natriuretic Peptide (ANP) Released from the atria in response to volume expansion. Inhibits sodium resorption in the renal tubules, promoting sodium excretion and diuresis. Induces systemic vasodilation. Long-Term Regulation of BP RAAS is a key regulator of BP: ○ Increased extracellular fluid volume raises CO and systemic vascular resistance (SVR), elevating BP. ○ Causes kidneys to excrete excess sodium and fluid. ○ Increased sodium osmolality triggers antidiuretic hormone (ADH) secretion, promoting water and sodium reabsorption. Angiotensin II increases SVR. ANP promotes sodium and water excretion by increasing glomerular filtration rate, while intrarenal arteriolar constriction enhances tubular sodium and water reabsorption.  PULM 1. Bronchiectasis - Primary Patho: - The infections that lead to bronchiectasis are usually the result of a defect in airway clearance that stems from airway obstruction, leading to distal pooling of secretions. - Allowing for chronic bacterial infections, which cause widespread damage to airway walls. Destruction of supporting smooth muscle and elastic tissue, the bronchi are markedly dilated, while smaller bronchioles are progressively obliterated as a result of fibrosis (bronchiolitis obliterans). - Destruction of smooth muscle and elastic tissue by inflammation stemming from persistent or severe infections leads to permanent dilation of bronchi and bronchioles. Chronic infections allowing for pulmonary wall damage - Risk Factors: - Persistent or severe infections. 50% of cases are idiopathic meaning there is dysfunctional host immunity to infectious agents leading to chronic inflammation - Uncommon but may also be related to: - Congenital or hereditary conditions that predispose to chronic infections (cystic fibrosis, intralobar sequestration of the lung, immunodeficiency states, primary ciliary dyskinesia, and Kartagener syndrome) - Severe necrotizing pneumonia caused by bacteria, viruses, or fungi; this may be a single severe episode or recurrent infection - Bronchial obstruction due to tumor, foreign body, or mucus impaction; in each instance the bronchiectasis is localized to the obstructed lung segment - Immune disorders: including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and the posttransplant setting (chronic rejection after lung transplant and chronic graft-versus-host disease after hematopoietic stem cell transplantation). - Hallmark s/s: - Cough, expectoration of foul smelling purulent sputum (sometimes bloody) fever, dyspnea, orthopnea (severe) cyanosis - Early morning coughing fits due to the change in position loosening the secretions after being flat all night - s/s are episodic and normally precipitated by upper GI infection or introduction of new pathogenic agents - Diagnostics: - Xray - Complications/Secondary Conditions: - Bronchiectasis usually affects the lower lobes bilaterally, particularly air passages that are vertical, and is most severe in the more distal bronchi and bronchioles. Sometimes dilating 4 times in size - Airway dilation and scarring - Allergic bronchopulmonary aspergillis - occurs in patients with asthma or cystic fibrosis - Hyperimmune response to the fungus Aspergillus fumigatus - high serum IgE levels, serum antibodies to Aspergillus - intense airway inflammation with eosinophils, and formation of mucus plugs, which play a primary role in the development of bronchiectasis 2. Emphysema - Primary Patho: “Irreversible enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls.” - Toxic injury and inflammation. Inhaled cigarette smoke and other noxious particles damage respiratory epithelium and cause inflammation, resulting in variable degrees of parenchymal destruction. Inflammatory mediators (including leukotriene B4, interleukin [IL]-8, TNF, and others)  are increased in the affected parts of the lung. Chronic inflammation also leads to the accumulation of T and B cells in affected parts of the lung - Protease-antiprotease imbalance. Several proteases are released from the inflammatory cells and epithelial cells breaking down connective tissue components. - Oxidative stress. Substances in tobacco smoke, alveolar damage, and inflammatory cells all produce oxidants, which may cause tissue damage, endothelial dysfunction, and inflammation. - Infection. Not an initiating cause but bacterial and/or viral infections may acutely exacerbate existing disease. - Four major types related to their anatomic distribution within the lobule - (1) centriacinar “centrilobular” (significant airflow obstruction). - most common form, 95% of clinically significant cases.The central or proximal parts of the acini, are affected. Distal alveoli spared - more common and usually more pronounced in the upper apical segments. In severe cases, the distal acinus may also be involved, making differentiation from panacinar emphysema difficult. - (2) panacinar “panlobular” (significant airflow obstruction) - associated with α1-antitrypsin deficiency and exacerbated by smoking. Acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli. More commonly in the lower and anterior margins of the lung, most severe at the bases. - (3) Distal acinar “paraseptal” - Underlies many cases of spontaneous pneumothorax in young adults. Proximal portion of the acinus is normal, and the distal part is predominantly involved. It occurs adjacent to areas of fibrosis, scarring, or atelectasis and is usually more severe in the upper half of the lungs. The characteristic finding is multiple enlarged airspaces, ranging from less than 0.5 cm to more than 2.0 cm in diameter, which sometimes form cyst-like structures. - (4) Airspace enlargement with fibrosis “irregular” - Acinus is irregularly involved, almost invariably associated with scarring. It occurs in small foci and is clinically insignificant. - Risk Factors: - Smokers and α1-antitrypsin deficiency - Hallmark s/s: - (s/s same as COPD so know the patho difference.) Emphysema is defined by irreversible enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls. - Pink Puffer, Barrel Chest with obviously prolonged expiration, forward hunching, pursed lip breathing. (SEE PIC UNDER COPD) - Diagnostics: - Large alveoli on cut section of lungs, chest x ray showing voluminous lungs that overlap the heart anteriorly - Apical blebs or bullae characteristic of irregular emphysema may appear in patients with advanced disease. - Even larger abnormal airspaces and blebs or bullae, which deform and compress the respiratory bronchioles and vasculature of the lung. - Microscopically, abnormally large alveoli are separated by thin septa with focal centriacinar fibrosis. - Vascular changes related to pulmonary hypertension stemming from local hypoxemia and loss of capillary beds. - Complications/Secondary Conditions: - Pneumothorax d/t bullae - Wt loss due to work of breathing - Compensatory hyperinflation- designates dilation of alveoli in response to loss of lung substance elsewhere - Hyperinflation occurs because an obstruction acts as a ball valve allowing air to enter on inspiration while preventing its exit on expiration or because collaterals bring in air behind the obstruction. - Obstructive overinflation can be life-threatening if the affected portion distends sufficiently to compress the adjacent uninvolved lung. - Bullous emphysema. large subpleural blebs or bullae form, often near the apex. Rupture of the bullae may give rise to pneumothorax.  - Interstitial emphysema. Entrance of air into the connective tissue stroma of the lung, mediastinum, or subcutaneous tissue. - Caused by alveolar tears that occur due to transient increases in intra-alveolar pressure, for example, during coughing. 3. Differentiate the types of asthma NON-ATOPIC ASTHMA EXERCISE-INDUCED DRUG-INDUCED OCCUPATIONAL ATOPIC ASTHMA ASTHMA ASTHMA ASTHMA Resp infections due to viruses Common in children and Aspirin-sensitive Triggered by: fumes IgE-mediated (Type I) (e.g., rhinovirus, parainfluenza adolescents asthma is an (epoxy resins, plastics) hypersensitivity reaction virus, and RSV) are common uncommon type Bronchospasm often occurs Organic and chemical Usually begins in childhood and is triggers in non-atopic asthma. dusts (wood, cotton, within 3 minutes after the end Occurs in individuals triggered by environmental Inhaled air pollutants such as of exercise; usually resolves with recurrent rhinitis platinum) allergens, such as dusts, pollens, tobacco smoke, sulfur dioxide, in 60 minutes and nasal polyps. cockroach or animal dander, and Gases (toluene) ozone, and nitrogen dioxide foods Typical symptoms include Exquisitely sensitive may also contribute to the Other chemicals dyspnea, wheezing, cough, to aspirin and NSAIDs PATHOGENESIS chronic airway inflammation (formaldehyde, and hyperreactivity in some chest tightness, excessive penicillin products) Triggers asthmatic Caused by a Th2-mediated IgE cases. mucus production attacks and urticaria. response to environmental Often have positive Heat loss, water loss, and allergens in genetically In some instance's attacks may Trigger asthma by skin test reactions to increased osmolarity of the predisposed individuals be triggered by seemingly inhibiting the protein allergens in the innocuous events, such as lower respiratory mucosa work environment cyclooxygenase Airway inflammation causes airway exposure to cold and even stimulate mediator release pathway of dysfunction through the release of from basophils and tissue Tends to have exercise. arachidonic acid potent inflammatory mediators and mast cells causing smooth progressively more metabolism, leading to partly through remodeling of the muscle contraction severe attacks with a rapid decrease in airway wall. subsequent exposures Running, jogging, and tennis prostaglandin E2 As the disease becomes more are the most common Trigger Type I severe, there is increased local stimulators hypersensitivity secretion of growth factors, which reactions induce mucous gland enlargement, Sensitization is smooth muscle proliferation, ineffective treatment angiogenesis, and fibrosis. 4. Pneumoconiosis- Occupational lung disease. (originally coined to describe the non-neoplastic lung reaction to inhalation of mineral dusts encountered in the workplace, now also includes disease induced by chemical fumes and vapors.) - Primary Patho: - Anthracosis- is the most innocuous coal-induced pulmonary lesion in coal miners and is also seen to some degree in urban dwellers and tobacco smokers. Inhaled carbon pigment is engulfed by alveolar or interstitial macrophages, which accumulate in the connective tissue adjacent to the lymphatics and in organized lymphoid tissue adjacent to the bronchi or in the lung hilus. - Risk Factors: - Dust retention. Any influence, such as cigarette smoking, that impairs mucociliary clearance significantly increases the accumulation of dust in the lungs. - Particle size. The most dangerous particles are from 1 to 5 µm in diameter because particles of this size can reach the terminal small airways and air sacs and deposit in their linings. - Particle solubility and cytotoxicity. small particles composed of injurious substances of high solubility are more likely to produce rapid-onset acute lung injury whereas larger particles are more likely to resist dissolution and may persist within the lung parenchyma for years. These tend to evoke fibrosing collagenous pneumoconioses, such as is characteristic of silicosis. - Particle uptake by epithelial cells allows direct interactions with fibroblasts and interstitial macrophages to occur. Some particles may reach the lymph nodes through lymphatic drainage directly or within migrating macrophages and thereby initiate an adaptive immune response to components of the particulates or to self-proteins modified by the particles or both.  - Activation of the inflammasome occurs following the phagocytosis of certain particles by macrophages. This innate immune response amplifies the intensity and the duration of the local reaction. - Tobacco smoking worsens the effects of all inhaled mineral dusts, but particularly those caused by asbestos. - Hallmark s/s: - gradual nonproductive cough. If cough is productive it is most likely smoking related rather than the pneumoconiosis - Diagnostics: - pathology of biopsied lung, xray showing irregular linear densities and with advancement of disease, honeycomb pattern - Complications/Secondary Conditions: - Asbestosis - proinflammatory crystalline hydrated silicates that are associated with pulmonary fibrosis and various forms of cancer. - Asbestos-related diseases include: Localized fibrous plaques or, rarely, diffuse pleural fibrosis. Recurrent pleural effusions. Parenchymal interstitial fibrosis (asbestosis). Lung carcinoma. Mesothelioma. Laryngeal, ovarian, and perhaps other extrapulmonary neoplasms, including colon carcinoma. Increased risks for systemic autoimmune diseases and cardiovascular disease also have been proposed. - Asbestos acts as a tumor initiator and a tumor promoter. Once phagocytosed by macrophages, asbestos fibers activate the inflammasome and stimulate the release of proinflammatory factors and fibrogenic mediators. - Silicosis - inhalation of proinflammatory crystalline silicon dioxide (silica) - slowly progressing, nodular, fibrosing pneumoconiosis. Currently, silicosis is the most prevalent chronic occupational disease in the world. - African Americans are at higher risk than Caucasians. - Phagocytosis activates the inflammasome leading to the recruitment of additional inflammatory cells and activates interstitial fibroblasts, leading to collagen deposition. - Silicosis is characterized in its early stages by tiny, barely palpable, discrete, pale to blackened (if coal dust is also present) nodules in the hilar lymph nodes and upper zones of the lungs. As the disease progresses, these nodules coalesce into hard, collagenous scars. Silicosis also is associated with an increased susceptibility to tuberculosis and a twofold increased risk of lung cancer. - Coal Workers’ Pneumoconiosis - inhalation of coal particles and other admixed forms of dust. - varying from asymptomatic anthracosis to simple coal workers’ pneumoconiosis with little to no pulmonary dysfunction. Complicated coal workers’ pneumoconiosis, or progressive massive fibrosis 5. COPD (chronic bronchitis since emphysema is already on here) - Primary Patho: - characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities caused by exposure to noxious particles or gasses. Two differing types are emphysema and chronic bronchitis. - Risk Factors: - Smokers, especially women and african americans. - Poor lung development early in life - exposure to environmental and occupational pollutants - airway hyperresponsiveness - certain genetic polymorphisms. - Secondary polycythemia → CLOT FORMATION - Hallmark s/s: - Mucus hypersecretion. Large airways hypersecrete mucus. D/t enlargement of the  submucosal glands in the trachea and bronchi. Involves histamine and IL-13. Marked increase in goblet cells in small airways leading to excessive mucus production causing airway obstruction. - Diagnostics: an important diagnostic test is spirometry, which typically shows an FEV1/FVC ratio of less than 0.7. - Complications/Secondary Conditions: - hypoxemia, pulmonary hypertension, and cor pulmonale due to significant lung dysfunction 6. Alpha-1 antitrypsin - Primary Patho: is an inherited disorder characterized by low serum levels of alpha-1 antitrypsin (AAT). Loss of AAT disrupts the protease-antiprotease balance in the lungs, allowing proteases, specifically neutrophil elastase, to act uninhibited and destroy lung matrix and alveolar structures - Risk Factors: Environmental factors, such as exposure to tobacco smoke, chemicals, and dust, about 1% of all patients with emphysema have this defect. - Hallmark s/s: SHOB, wheezing, chronic cough with phlegm, chest pain, rapid heart rate, weight loss, loss of appetite, swelling of the feet or belly, yellowish discoloration of the skin and whites of the eyes, vomiting of blood, or blood in stools. In rare cases, AAT deficiency can cause a skin disease called panniculitis, which results in painful red bumps on the skin that may break open and leak fluid or pus - Diagnostics: blood test to measure AATD in blood, genetic testing, x-rays and CT scans, pulmonary function test - Complications/Secondary Conditions: COPD, emphysema, cirrhosis, liver failure, pulmonary HTN, heart failure, inflammation of the fat under the skin 7. Pneumothorax - Primary Patho: occurs when air or gas enters the pleural space, causing the lung to collapse - Risk Factors: smoking, tall thin individuals, those over 60, men are more likely, family history, lung disease such as asthma or COPD, injury - Hallmark s/s: - Small pneumothoraces (38°C Pulmonary function tests (PFTs) may indicate (100.4°F), HR >100 beats/min, or RR >24 chronic airway obstruction. breaths/min may suggest other respiratory issues like pneumonia. Complications Symptoms typically resolve within 3 weeks; Progressive lung dysfunction. however, investigation for pneumonia may be Hypoxemia and respiratory failure. warranted if vital signs are abnormal. Pulmonary hypertension and cor pulmonale. Usually mild and self-limiting, but can lead to Increased risk of respiratory infections. further respiratory infections if not managed properly. 14. Pleural Effusion - Patho: Accumulation of pleural fluid due to various causes, including: Increased hydrostatic pressure (e.g., congestive heart failure) Increased vascular permeability (e.g., pneumonia) Decreased osmotic pressure (e.g., nephrotic syndrome) Increased intrapleural negative pressure (e.g., atelectasis) Decreased lymphatic drainage (e.g., mediastinal carcinomatosis) - Risk Factors: Heart failure, pneumonia, kidney disease, or malignancies - Hallmark s/s: Symptoms vary depending on the cause and size of the effusion: May be asymptomatic with 0.5 mg/dl) Low in protein (ratio Presence of blood Chyle is milky white Causes: malignancies,