17. Shock & IHD.pdf

Lecture 17 – Shock and Ischemic Heart Disease Edema = excess fluid in interstitial spaces Usual causes: blood hydrostatic pressure increases, drop in blood oncotic pressure, increased vascular permeability, blockage of lymphatic flow Pathological: ○ Transudate → low in prote...

Lecture 17 – Shock and Ischemic Heart Disease Edema = excess fluid in interstitial spaces Usual causes: blood hydrostatic pressure increases, drop in blood oncotic pressure, increased vascular permeability, blockage of lymphatic flow Pathological: ○ Transudate → low in protein, low cellular content, caused by pressure imbalances ○ Exudate → high protein, high cellular content, caused by inflammation and vessel damage Starling Forces → movement of fluid across capillary walls Edema and Microcirculation Oncotic pressure – pull force that draws water into the blood vessels, mainly created by large proteins Hydrostatic pressure – push force that moves water out of the blood vessels into surrounding tissues, generated by pressure of blood against walls of vessels (especially in arteries) A. Normal → Filtration and Reabsorption: At the arterial end, fluid is filtered into the interstitial space at about 14 mL/min due to hydrostatic and oncotic pressure differentials. At the venous end, 12 mL/min is reabsorbed, and 2 mL/min is drained by the lymphatics, which also remove proteins. B. Hydrostatic Edema → Increased Hydrostatic Pressure: When hydrostatic pressure at the venous end rises, reabsorption decreases. If lymphatic drainage cannot handle the extra fluid, edema forms. C. Oncotic Edema → Low Oncotic Pressure: Reduced oncotic pressure (e.g., due to albumin loss) lowers fluid reabsorption, leading to fluid buildup and edema. D. Inflammatory/Traumatic Edema → Vascular Injury: Endothelial damage increases vascular permeability, causing fluid to leak and resulting in localized or systemic edema. E. Lymphedema → Lymphatic Obstruction: Blocked lymphatic drainage prevents fluid and protein removal, raising oncotic pressure in the interstitial space and leading to fluid accumulation. How do starling forces regulate fluid exchange between capillaries and surrounding tissue? Arterial Side: The capillary hydrostatic pressure (PcP_cPc​) is higher than the capillary oncotic pressure (πc\pi_cπc​), which pushes fluid out of the capillary into the interstitial tissue. This fluid nourishes surrounding tissues. Venous Side: Here, PcP_cPc​drops and is now lower than πc\pi_cπc​, so the oncotic pressure pulls fluid back into the capillary from the interstitial space. Not all fluid reenters the capillary; any excess is drained by the lymphatic system, preventing edema. Edema Causes 1. Increased Hydrostatic Pressure: Caused by increased arteriolar blood pressure (e.g., malignant hypertension) or decreased venous drainage (regional or global, such as in congestive heart failure). Certain endocrine disorders like Cushing’s, Conn’s syndrome, and pheochromocytoma can also increase hydrostatic pressure. 2. Increased Sodium and Water Retention: Can occur from dietary sodium retention or kidney pathologies affecting sodium elimination. Endocrine conditions like inappropriate ADH secretion or excessive aldosterone from adrenal pathologies can contribute to retention. 3. Reduced Lymphatic Drainage: Caused by malignancies infiltrating lymph nodes, lymph node removal during surgeries, or infections like filiariasis, which can lead to conditions like elephantiasis.  4. Decreased Oncotic Pressure: Mostly due to low plasma albumin levels, as seen in nephrotic syndrome (protein leakage through glomeruli), liver failure, or malnutrition, which reduces the ability to retain fluid within the capillaries. 5. Endothelial Damage/Leakiness: Inflammatory processes or damage to endothelial tissue can cause edema. Pulmonary edema is particularly dangerous as it impairs breathing. General Clinical Features of Edema Dependent on type of edema – more noticeable in areas of the body that are most inferior to the heart Renal disease can cause generalized edema apparent in areas that contain “looser” CT (anasarca) Pulmonary and brain edema → most severe ○ Edema is not just a symptom, but a causative factor in the pathophysiology ○ Unique interaction of microvasculature and air spaces (lungs), and the inflexible cranial cavity (brain) result in more severe consequences Anasarca Generalized, severe edema throughout the body Associated with systemic diseases such as HF, liver failure, nephrotic syndrome → extensive fluid retention Angioedema Rapid, localized swelling typically due to an allergic reaction or hereditary condition Affects deeper layers of the skin and mucous membranes – face, throat, extremities Hyperemia → This is an active process caused by arteriolar dilation, increasing blood flow in response to metabolic needs or inflammation (e.g., in exercise or warming up after being cold). Affected tissues turn red (erythema) due to oxygenated blood filling the vessels. Congestion → This is a passive process resulting from impaired blood outflow, either systemically (as in heart failure) or locally (e.g., venous obstruction). Congested tissues appear dusky or reddish-blue (cyanosis) due to accumulated deoxygenated blood. Over time, red blood cells may leak out into tissues and break down, leading to hemosiderin deposits (iron-storage pigment from hemoglobin degradation), which adds a brownish color. Chronic Congestion Long-term congestion causes chronic hypoxia, leading to cell degeneration, tissue fibrosis, and small hemorrhages. Macrophages accumulate hemosiderin as they clear red cell debris, especially evident in chronic conditions like pulmonary and hepatic congestion: ○ Pulmonary Congestion: In acute cases, alveolar capillaries are engorged; chronically, septa thicken, and macrophages with hemosiderin ("heart failure cells") accumulate. ○ Hepatic Congestion: Acutely, blood distends liver sinusoids, and hepatocytes can degenerate. Cells closer to arterial circulation are less affected but may undergo fatty change due to reduced oxygen. Venous Congestion venous ulcers are leg ulcers caused by problems with BF in leg veins Venous congestion leads to ulcers primarily through a cycle of increased venous pressure, fluid accumulation, reduced BF, and tissue breakdown White vs. Red Infarct Infarct - necrosis due to lack of blood flow ○ This lack of blood flow results in insufficient oxygen (ischemia) and nutrient delivery to the tissues, leading to cell damage and death  White Infarcts: ○ Pale, well-defined areas of necrosis. ○ Occur in organs with a single blood supply. ○ Results from arterial occlusion. Red Infarcts: ○ Reddish areas of necrosis. ○ Occur in organs with dual blood supply or collateral circulation ○ Results from venous occlusion Tissue Specific Infarcts Pulmonary infarcts – complication of pulmonary embolism in the setting of CHF ○ Difficulty providing oxygenated blood to the larger lung structures ○ Necrosis & hemorrhage in affected lung Intestinal infarcts – consequences of blocking arterial flow or impaired venous flow due to obstruction, strangulation volvulus Splenic infarct – wedge-shaped, white infarcts located under the capsule SHOCK Final common pathway for several potentially lethal clinical events (e.g., severe hemorrhage or dehydration, extensive trauma or burns, myocardial infarction, massive pulmonary embolism, etc.) A profound hemodynamic and metabolic disturbance in which the circulatory system fails to supply the microcirculation adequately, with consequent inadequate perfusion of vital organs Categories of Shock Hypovolemic → Hemorrhage, dehydration, third-spacing of fluid ○ Too little fluid in vessels Distributive → Anaphylaxis, spinal shock ○ Too many vessels dilated, not enough blood to keep the pressure up Cardiogenic → Heart attack, heart failure, dysrhythmias ○ Heart isn’t working Obstructive → Cardiac tamponade, pulmonary embolus, pneumothorax ○ Heart is working, but blood can’t leave the heart  Septic → Shock is due to poor blood distribution AND inflammatory damage Septic Shock → severe and potentially life-threatening – result of sepsis (extreme response to infection) Body’s response to infection leads to widespread inflammation, causing significant changes in blood circulation 7 resulting in dangerously low BP and inadequate BF to vital organs Septic shock lacks a single diagnostic test; instead, various scoring systems help identify high-risk patients. Key features include: ○ Dysregulated Vascular Reflexes: This leads to inappropriate vasodilation and edema, often resulting from endothelial damage. ○ Elevated Proinflammatory Cytokines: These can negatively affect tissues, particularly the heart and kidneys. ○ Leukocyte Migration: White blood cells move into various organs, causing dysfunction. ○ Coagulation and Complement Activation: There is inappropriate activation of these systems, contributing to the condition's severity. Stages of Shock (applies to all causes) 1. Stage I → compensated a. Tachycardia: Increased heart rate occurs, but blood pressure remains normal. b. Physiology: When cardiac output or blood volume decreases (e.g., due to hemorrhage), compensatory mechanisms activate. Baroreceptors detect lower blood pressure, stimulating the sympathetic nervous system (SNS) to release catecholamines, which increase heart rate and contractility to maintain blood flow to vital organs. c. Compensation: The body’s mechanisms keep blood pressure stable despite the heart rate increase. 2. Stage II → decompensated a. Failure of Compensation: The body can no longer effectively maintain blood flow to tissues. b. Symptoms: Tachycardia continues, but hypotension develops. c. Consequences: This stage is more difficult to reverse, leading to a cycle of tachycardia, hypotension, diminished organ perfusion, and metabolic acidosis. d. Irreversibility Risk: Prolonged decompensation increases the likelihood of irreversible organ damage. Shock – General Clinical Features Hypovolemic and cardiogenic shock – hypotension, weak/rapid pulse, tachypnea, cool/clammy/cyanotic skin Septic shock – same as above, but skin may initially be warm and flushed bc of peripheral vasodilation Ischemic Heart Disease (IHD) Definition: IHD occurs when blood supply to the myocardium is insufficient for its metabolic needs, primarily due to atherosclerosis in the coronary arteries. Other causes can include aneurysms, autoimmune attacks, and vasospasm.  Epidemiology: IHD is the leading cause of death globally, responsible for approximately 7 million deaths annually. In the U.S., someone dies from a myocardial infarction every minute Pathogenesis: ○ IHD arises from: Progressive Narrowing: Atherosclerosis leads to hypoperfusion and heart failure. Sudden Occlusion: Ruptured atherosclerotic plaques can cause acute clot formation, leading to myocardial infarction. ○ Exacerbated by factors increasing the heart’s metabolic demand, such as increased heart rate, wall tension, and contractility. Common causes: ○ Coronary atherosclerosis is the primary cause (90% of cases). Other factors, like hypertension, can exacerbate the condition. ○ Conditions that influence supply of blood, conditions that influence availability of oxygen in blood, increased oxygen demand (increased cardiac work) Pathophysiologic concepts: ○ Healthy individuals can significantly increase myocardial blood flow during intense exercise. ○ Impairment of maximal blood flow occurs with about 75% stenosis, while resting flow is unaffected until over 90% occlusion. Atherosclerosis Over time, atherosclerotic plaques form in coronary arteries, narrowing them (stenosis). During increased physical activity, this can lead to angina pectoris (reversible chest pain). Plaque rupture can result in acute clot formation, causing either total or partial occlusion of the artery, leading to ischemia. Acute clot formation (Thrombosis) – after plaque ruptures, the body responds as if there is an injury and activates coagulation cascade – a rapid process, can partially or completely block the artery Embolization – downstream blockage, parts of the thrombus/plaque break off and travel downstream as an embolus (can lodge in smaller coronary arteries, blocking flow) Ischemia & Infarction Ischemia refers to insufficient BF, and if not resolved quickly it can lead to myocardial infarction (heart muscle death), which is irreversible Factors that Affect Metabolic Demands: Heart Rate: Faster rates increase energy use. Wall Tension: Increased in dilated hearts (Laplace’s law). Contractility: Strength of heart contractions, influenced by intracellular calcium levels. Types of IHD Presentation Stable Angina: Predictable chest pain due to stable plaques during exertion. Acute Coronary Syndromes (ACS):  ○ Unstable Angina: Unpredictable pain due to variable blockage. ○ Non-ST Elevation Myocardial Infarction (NSTEMI): Partial blockage with elevated troponins but no ECG elevation. ○ ST Elevation Myocardial Infarction (STEMI): Complete blockage leading to full-thickness damage, evident on ECG. Pathophysiology of Unstable Angina Prinzmetal angina → form of chest pain caused by temporary spasms in coronary arteries ○ Technically a type of unstable angina, but has a much better prognosis Caused by coronary artery spasm, early morning (unrelated exertion), does not usually cause infarction, responds well to vasodilators, typical patient is younger women Adaptations to Chronic Ischemia Hypertrophy of Cardiac Myocytes: Chronic ischemia leads to cardiac myocyte hypertrophy and changes in contraction mechanisms, resulting in ischemic cardiomyopathy. Coronary Collateral Circulation: In cases of severe atherosclerosis, collateral blood vessels develop to maintain blood flow, preventing complete infarction or limiting infarct size during occlusion. Pathological Pathways during Acute Infarct Vulnerability of Subendocardial Vessels: The inner small blood vessels are most at risk during systole due to high pressure and are the last to relax. The heart receives oxygenated blood primarily during diastole, particularly affecting the inner myocardium. Types of Infarcts Transmural Infarction: Caused by blockage of a major epicardial vessel, affecting the entire wall thickness, typically seen in STEMI. Subendocardial Infarction: Resulting from unstable or partial plaques and global hypoperfusion, affecting only the subendocardium, leading to NSTEMI. Progression of Coronary Artery Disease (CAD) 1. Normal Coronary Artery: Unobstructed arteries allow normal blood flow. 2. Atherosclerosis: Fatty plaques build up, narrowing the lumen. 3. Fixed Coronary Obstruction (Typical Angina): Stable narrowing that provides adequate blood flow at rest but may lead to stable angina during exertion. 4. Plaque Disruption: Unstable plaques can rupture, forming thrombi that may occlude the artery. 5. Severe Fixed Coronary Obstruction (Chronic Ischemic Heart Disease): Severe narrowing can cause unstable angina or angina at rest. 6. Types of Thrombosis: a. Mural Thrombus: Variable obstruction can lead to unstable angina or subendocardial MI. b. Occlusive Thrombus: Complete blockage causing acute transmural MI or sudden cardiac death. Pathophysiological Development of MI Initial Minutes: Early cellular changes include swelling and loss of glycogen, resulting in "stunned myocardium" where cells cannot contract but are not yet dead (reversibility) 30-60 Minutes Post-Ischemia: Myocyte injury becomes irreversible, characterized by swollen mitochondria, disrupted cell membranes, and release of intracellular substances, indicating coagulative necrosis. Necrosis Mitochondrial Pathway ○ ATP Depletion: Energy-dependent functions are impaired due to a lack of ATP, leading to cell injury and necrosis. ○ ROS Damage: Increased reactive oxygen species (ROS) further contribute to mitochondrial dysfunction. Cellular Membrane Pathway: Membrane Damage → Injury to plasma and lysosomal membranes results in enzyme leakage, impaired cellular function, and ultimately necrosis.  Cell Cycle Arrest & Apoptosis: DNA Damage → DNA injury can trigger apoptosis, leading to programmed cell death. Calcium Entry: Increased Intracellular Calcium → Membrane damage or cellular stress causes calcium influx, which alters mitochondrial permeability and activates various cellular enzymes, promoting necrosis. Mitochondrial Damage Can be damaged by free radical attack If levels of systolic calcium increase too high in cell, MPTP can open ○ Loss of mitochondrial membrane potential, releases H+, further increase in cytoplasmic Ca2+, inability to generate ATP, ultimately necrosis ○ Poorly understood, but important Pathophysiological Development of MI Day 2-3: Neutrophil Infiltration: Neutrophils enter necrotic tissue, accessing only the edges of the infarct where blood flow persists. Tissue Changes: Interstitial edema and microscopic hemorrhages appear. Necrotic muscle cells show loss of nuclei and striations, surrounded by acute inflammatory cells. Day 5-7: Macrophage Replacement: Neutrophils are replaced by macrophages, and myofibroblasts begin collagen deposition, forming scar tissue. This is a dangerous period due to weakened myocardial walls. Week 1 and later: Collagen Deposition: Continued collagen accumulation creates scar tissue. By week 3, the area is mostly scar tissue, with previous macrophages and new vessels having disappeared. Scar Remodeling: The scar becomes more solid over time, with a dense, acellular collagen matrix at the edges, clearly demarcated from viable myocardium. Reperfusion Injury If blood flow is restored before extensive myocardial cell death, reperfusion injury can occur – involving: ○ Contraction Band Necrosis: Characterized by hypercontracted and disorganized sarcomeres with thickened Z disks, caused by calcium influx and ROS generation when blood flow resumes. ○ Outcome: Some myocardial cells may still die despite restored flow, but restoring blood flow is generally beneficial. Inflammatory damage also contributes to reperfusion injury. Transmural Infarct → Result from large, permanent occlusion of a coronary artery, often associated with STEMI. Non-Transmural Infarct → Result from various factors such as global hypoxia or transient occlusion, associated with NSTEMI. Which Vessels are most often involved in MI: Left Anterior Descending Artery (50%): Causes apical, anterior, and anteroseptal infarcts. Right Coronary Artery (30-40%): Leads to posterior basal infarcts and affects the posterior 1/3 to 1/2 of the interventricular septum (inferior infarcts). Left Circumflex Artery (15-20%): Affects the lateral wall of the left ventricle. IHD – Clinical Manifestations Symptoms: ○ Asymptomatic: some individuals may not experience symptoms ○ Chest pain (angina pectoris)  Can radiate to the left arm, shoulder, or interscapular area; may mimic gastroesophageal reflux. Characterized as "crushing" or squeezing rather than sharp. Other Symptoms: Dyspnea (shortness of breath), fatigue, palpitations, diaphoresis (excessive sweating), symptoms of congestive heart failure Presentation Types: ACUTE Stable Angina: Predictable pain associated with exertion, relieved by rest or nitroglycerine within 3-20 minutes. Unstable Angina: New, changing, or severe pain not relieved by rest/nitroglycerine, occurring at rest or with increasing intensity. Myocardial Infarction (MI): Death of heart muscle, classified as ST-elevation (STEMI) or non-ST-elevation (NSTEMI) based on ECG. Sudden Cardiac Death: Abrupt loss of heart function due to dysrhythmia, often related to long-term ischemic heart disease. CHRONIC Heart Failure: Often referred to as ischemic cardiomyopathy, develops from ongoing ischemia. Clinical Features of MI Pain Severity: MI pain is often more severe than that of angina, though there are exceptions. Atypical Presentations: MI can present as heartburn, interscapular pain, or acute severe fatigue, and may not always involve classic chest pain. Diagnosis of IHD ECG: Used to identify specific patterns associated with IHD and MI. Cardiac Enzymes: Troponin (T and I) and CK-MB are reliable markers for myocardial injury. Angiogram: Visualizes coronary artery blockages. Echocardiogram: Assesses heart function and structure. Nuclear Medicine Imaging: Certain isotopes indicate damaged or ischemic cardiac tissue. General Treatment of IHD – address energy supply-demand imbalance Antiplatelet Agents (e.g., ASA) → Reduce thrombus risk and prevent enlargement of existing thrombi. Antihypertensives → Especially ACE inhibitors. Beta Blockers → Reduce heart workload. Calcium Channel Blockers → Decrease contractility and provide some vasodilation. Nitroglycerine → Decreases preload and afterload, acting as a coronary vasodilator. Blood Glucose and Lipid Control → Essential for overall management. Revascularization Procedures → PCI or CABG may be indicated in some cases; stenting has limited benefit in stable angina cases. Treatment of MI NSTEMI → No use of “clot-busting” drugs (e.g., tissue plasminogen activator).  STEMI → clot-busting drugs: Thrombolytics (e.g., reteplase, alteplase) can be life-saving. Revascularization → Both NSTEMI and STEMI can benefit from procedures like angioplasty or stenting. Requires access to a skilled medical team. Immediate Resuscitation → Critical for survival as dysrhythmias can lead to death if not addressed promptly. Chronic Medications → Similar to those used for stable and unstable angina. Complications of IHD Acute Myocardial Infarction ○ Mortalities rates: 25-35% die acutely, primarily from: dysrhythmias (ventricular fibrillation), heart block, heart failure, asystole (cardiac arrest) Post-Infarct Risks ○ Increased mortality days to months after the event due to: life-threatening dysrhythmias, cardiac rupture (highest risk 3-7 days post-MI due to necrosis), poor wall motion leading to clot development, pericarditis