Path Review PDF

Introduction The speaker apologizes for the wrong time on their outlook calendar and mentions adjustments made to the exam. They discuss blood vessels, thrombus, embolus, and post mortem clots. They explain the terms hemostasis, thrombosis, and primary hemostasis, emphasizing the goal of attracting...

Introduction The speaker apologizes for the wrong time on their outlook calendar and mentions adjustments made to the exam. They discuss blood vessels, thrombus, embolus, and post mortem clots. They explain the terms hemostasis, thrombosis, and primary hemostasis, emphasizing the goal of attracting platelets to the injury site. Components of platelets • Platelets contain granules that help with clot formation • Granules contain different substances that aid in platelet adhesion and aggregation Steps in secondary hemostasis • Platelets strengthen the clot by activating the coagulation cascade • They use fibrinogen to stick to each other and form fibrin, strengthening the clot • Antithrombotic counter regulation limits the growth of the clot to prevent excessive clot formation Thrombosis and Virchow's triad ends • Thrombosis is the intravascular coagulation of blood • Virchow's triad identifies three factors that predispose to thrombosis: endothelial injury, abnormal blood flow, and hypercoagulability • Endothelial injury can result from trauma, inflammation, or dysfunctional endothelium • Abnormal blood flow, such as stasis or turbulence, can contribute to thrombosis deeplegvein arterial • Hypercoagulability, which promotes excessive clotting, can also increase the risk of thrombosis Genetic mutations and factors that predispose to blood clot formation • Genetic mutations and coagulation cascade abnormalities increase the risk of blood clot formation • Certain medications, like older formulations of oral contraceptives, can also increase the risk of blood clots Location and attachment of thrombi • Thrombi can develop in cardiac chambers or in the aorta • Thrombi are usually attached to the underlying vessel or heart wall • Dislodged clots that travel to another location are called emboli Causes of thrombosis • Atherosclerotic plaques can lead to thrombus formation and vessel occlusion • Post-mortem clots are unattached and not clinically significant Characteristics of thrombi • Thrombi exhibit lamination with alternating layers of platelets, fibrin, and red blood cells • Active thrombi show lines of zone, indicating an ongoing process Differences between venous and arterial thrombi • Venous thrombi are more likely due to stasis, while arterial thrombi are more likely due to injury or turbulence • Deep vein thrombosis (DVT) is commonly associated with venous stasis • Arterial thrombi can occur at sites of turbulence, such as the left anterior descending coronary artery Formation and consequences of thrombi • Thrombi can completely obstruct blood flow, causing tissue ischemia or infarction • Immediate medical attention is required to prevent serious complications Consequences of venous thrombi • They can lead to congestion and edema • Deep leg vein thrombi cause swelling in the legs Consequences of arterial thrombi • They can lead to infarction due to the disruption of blood supply • Infarctions can occur in various organs Embolism • • • • Deep leg vein thromboembolism (DVT) is a major risk, especially during long flights Arterial thrombi can also cause embolism The majority of emboli are from deep leg veins Embolism can also be caused by fat, air, amniotic fluid, or foreign bodies Specific embolism types • Fat embolism: Usually small amounts of fat, 10% of people with fat embolism experience symptoms • Air embolism: Can occur during deep-sea diving or rapid ascents, causes nitrogen bubbles in the blood • Amniotic fluid embolism: Rare, can happen during labor Breakdown • Emboli can come from various sources including deep leg veins, amniotic fluid, foreign bodies, and drug abuse • The most common source of emboli is deep leg veins • Emboli can travel through the heart and get caught in the lungs due to the decreasing diameter of blood vessels • Smaller vessels in the lungs can become blocked, causing infarction • Saddle embolus refers to an embolus that blocks both sides of the lungs and can be deadly • Embolism from the heart can travel to systemic circulation, potentially causing issues in organs like the brain or small intestine • Pulmonary emboli are often clinically silent, but large clots can cause infarction • Edema can have different causes, including hypoproteinemia Causes of edema • Proteinemia - loss of albumin due to renal issues or sodium retention • Lymphatic obstruction - example: filarial worms • Treatment of certain cancers or invasion of lymphatics by cancer Types and distributions of edema • Dependent edema - mainly in the legs, commonly seen in right-sided congestive heart failure • Generalized edema - affects all body parts equally, can result from low protein levels • Pitting edema - when pressing on the skin leaves a temporary imprint, caused by inadequate protein levels in the blood • Pulmonary edema - fluid accumulation in the lungs, commonly associated with left-sided heart failure Passive causes of edema can lead to cyanosis • Increased inflow to tissues during inflammation (hyperemia) • Congestion Retinal Vein Occlusions • • • • Central retinal vein occlusion leads to bleeding in parts of the retina In a central retinal vein occlusion, bleeding can be observed in all four corners of the retina In a branch retinal vein occlusion, bleeding is more localized in a corner Thrombus formation in the vein draining the retina leads to congestion, edema, and hemorrhage Hemorrhage Types • • • • • • Petechiae are tiny hemorrhages into the skin, similar to the size of dot markings Purpura are larger than petechiae, showing as larger areas of hemorrhage Ecchymoses are even larger, usually over a centimeter or two, and typically occur after trauma Hematoma refers to a collection of blood in a tissue, often seen as a bruise Bleeding within body cavities is referred to as hemothorax, hemoperitoneum, etc. Jaundice can result from massive breakdown of red blood cells, leading to bilirubin accumulation Clinical Significance of Bleeding • Volume of bleeding determines the clinical impact • Large internal bleeds can cause hypovolemic shock, resulting in low blood pressure • Subcutaneous bleeding may be trivial, but cerebral bleeding can be fatal • Chronic blood loss can lead to iron deficiency anemia Shock and Hypotension • Shock is cardiovascular collapse characterized by systemic hypoperfusion • Hypotension, low blood pressure, can contribute to inadequate blood supply to tissues • Causes of hypotension include bleeding, poor heart pumping, anaphylactic shock, and loss of vascular tone Disseminated Intravascular Coagulation (DIC) • DIC is widespread activation of the coagulation system and release of clotting-promoting substances • It results in the formation of numerous clots throughout the body Main triggers of DIC (Disseminated Intravascular Coagulation) • Obstetrical complications • Infections • Cancer Hypertension • • • • • • Definition: systolic blood pressure above 130 and diastolic blood pressure above 80 Early recognition is important as there are usually no symptoms Affects a large percentage of the population, about a quarter Idiopathic or essential hypertension is most common, without a clear cause Secondary hypertension can be caused by kidney issues or adrenal gland problems Genetic and environmental factors play a role Consequences of hypertension • Aortic dissection and cerebrovascular hemorrhage are possibilities • Associated with two types of small blood vessel diseases: Hyaline arteriosclerosis and hyperplastic arteriosclerosis Change in small bloodvessels • Hyaline arteriosclerosis leads to thickening of arterial walls and is common in elderly patients and those with diabetes Impact of Malignant Hypertension: • • • • 200 120mmHg Malignant hypertension is a severe form of high blood pressure that can be life-threatening It can lead to retinal hemorrhage, renal failure, and other complications If left untreated, it can result in death within 1 to 2 years Patients may present to the emergency department with extremely high blood pressure levels Changes in Vessels in Malignant Hypertension: • In malignant hypertension, vessels may show a characteristic change known as "onion skinning" or lamination of the vessel lining • This causes narrowing of the vessels Link Between Hypertension and Atherosclerosis: • • • • • Hypertension is a risk factor for atherosclerosis Atherosclerosis is characterized by the formation of lesions called atheroma in the vessel lining Hypertension causes injury to the vessels, promoting the formation of atheroma Atheroma consists of cholesterol, fat, macrophages, and smooth muscle cells Macrophages and smooth muscle cells consume cholesterol and form foam cells, leading to inflammation and fibrosis Risk Factors for Atherosclerosis: • • • • Hypertension Smoking Hyperlipidemia Endothelial dysfunction Development of Atherosclerosis • Everyone develops fatty streaks (precursor lesions) for atherosclerosis in their first decade of life • These fatty streaks occur at branch points due to turbulence • Fatty streaks contain lipid deposits and foam cells (macrophages with fat) • Only some fatty streaks progress to atherosclerotic plaques Factors Increasing Risk of Atherosclerosis • Locations prone to atherosclerotic plaques: aorta, carotid arteries, iliac arteries, coronary arteries • Most common location: abdominal aorta, followed by thoracic aorta and coronary artery • Locations usually spared: upper extremities, mesenteric arteries, renal arteries (except at branch points) • Atheromas (plaques) often undergo calcification Risk Factors for Atherosclerosis • • • • Age: incidence of MI increases fivefold after 40 years Gender: males more likely due to estrogen's protective effects Genetics: familial hypercholesterolemia increases cholesterol levels Hyperlipidemia: high cholesterol and saturated fat intake • LDL and HDL: LDL transports cholesterol to tissues, while HDL removes cholesterol from plaques and takes it to the liver (higher HDL and lower LDL desired) • Factors promoting high density lipoproteins: exercise, not smoking, maintaining a healthy weight Symptoms and risk factors Aranssenat • White or gray ring around the periphery of the iris can indicate high cholesterol • Hypertension is a major risk factor for atherosclerosis • Cigarette smoking and diabetes increase the risk Complications of atherosclerosis • • • • Rupture of plaques can lead to thrombus and infarction Rupture of the cap can cause hemorrhage and promote an aneurysm Aortic dissection is a tear in the intima, leading to bleeding into the vessel An aneurysm is the ballooning of a vessel due to weakened wall components Aneurysms dialation of bloodvessel • • • • Common location for atherosclerotic aneurysms is the abdominal aorta Large aneurysms over six centimeters have a high risk of rupture They can impinge other vessels and lead to clot formation Aneurysms can also occur in the eye and cause sudden vision loss Dissecting aneurysms • Bleeding leads to separation of vessel layers • This can compress the vessel, leading to infarction Ascending and Descending Aorta • The ascending aorta experiences high stress, while the type A and type B aortic dissections are more likely to occur in the descending aorta • The most common locations for aortic dissections are the abdominal aorta and the thoracic aorta • Aortic dissecting aneurysms are associated with Marfan syndrome, which is characterized by a weakening of the aortic media due to a frilling defect and deficiency in Elastin Factors and Symptoms • Hypertension is a risk factor for aortic dissections • Aortic dissections are more common in males and individuals between the ages of 40 and 60 • Symptoms of aortic dissection include excruciating pain, sweating, dyspnea, weakness, and potential loss of consciousness Complications and Other Aneurysms • The most common cause of death in aortic dissections is rupture into a body cavity, such as hemopericardium • Aneurysms called berry aneurysms can cause subarachnoid hemorrhage and are associated with adult polycystic kidney disease Introduction The learning objectives of the Renal and Male Urogenital System Disorders course at KYCO include understanding kidney function tests, azotemia causes, clinicopathologic features of nephritic and nephrotic syndrome, urinary tract infection, renal cell cancer, BPH and prostate cancer, and the limitations of Prostate-Specific Antigen. The kidney functions include endocrine control, metabolic waste excretion, drug metabolism, acid/base balance, and blood pressure control. The renal filtration barrier retains proteins and larger particles while allowing the passage of water and small solutes. q size andcharge Kidney Function Tests disease belowGoiskidney • GFR is the best test to measure kidney function and determine the stage of kidney disease • Other tests include BUN and creatinine GFR d aBunher I don'twantthisinblood Azotemia and its causes • Azotemia can be divided into pre-renal, renal, and post-renal causes • Common causes of each include: excessbloodloss I dBP • Pre-renal: dehydration, hypovolemia doesnot use hypertension • Renal: acute tubular necrosis, glomerulonephritis • Post-renal: urinary tract obstruction Azotemiatclinicalmanifestations uremia Nephritic and Nephrotic Syndrome • Nephritic syndrome: characterized by hematuria, proteinuria, and hypertension • Nephrotic syndrome: characterized by heavy proteinuria, hypoalbuminemia, and edema Urinary Tract Infection (UTI) • UTI is an infection in any part of the urinary system • Risk factors include female gender, urinary stasis, catheters, and sexual activity Renal Cell Cancer • Risk factors include smoking, obesity, and hypertension • Histopathological features: clear cell carcinoma is the most common subtype • Symptoms may include hematuria, flank pain, and weight loss BPH and Prostate Cancer • BPH (benign prostatic hyperplasia): enlargement of the prostate gland • Prostate cancer: malignant growth of cells in the prostate gland • PSA (Prostate-Specific Antigen) has limitations as a screening test for prostate cancer Structure and Function of the Kidney • The kidney performs endocrine functions, regulates fluid and solute balance, excretes waste products, and controls blood pressure • The glomerular filtration barrier filters the blood, retaining most proteins and larger particles Kidney function and GFR • The GFR number indicates kidney function • As kidney disease advances, GFR decreases Kidney function tests - BUN and Creatinine • • • • BUN (Blood Urea Nitrogen) measures metabolism of amino acids Urea is taken away to the kidneys and excreted in urine Creatinine is a waste product from muscle wear and tear Kidneys filter out most creatinine and dispose of it in urine Azotemia and Uremia • Azotemia refers to elevated levels of blood urea nitrogen and creatinine • Indicates decreased glomerular filtration rate (GFR) • Azotemia, along with clinical manifestations, can lead to uremia Causes of azotemia • Prerenal: decreased blood flow to the kidneys • Renal: direct kidney damage by inflammation, toxins, or reduced blood supply • Postrenal: sudden obstruction of urine flow Symptoms of acute renal failure (ARF) • Dark urine, confusion, lower urine output, itching skin • Swelling in lower extremities, unexplained nausea • In severe cases, seizures and loss of consciousness Chronic kidney disease (CKD) • Caused by diabetes, high blood pressure, glomerulonephritis, etc. • Can result from prolonged obstruction of the urinary tract • Symptoms include nausea, vomiting, loss of appetite Most common causes of chronic renal disease • • • • Diabetes and hypertension Obesity and osteoarthritis Lack of exercise and hypercholesterolemia High salt diet and malnutrition Symptoms of chronic kidney disease • Nausea, vomiting, loss of appetite CKD Symptoms • • • • • • • Fatigue and weakness Sleep problems Changes in how much you urinate Decreased mental sharpness Muscle twitches and cramps Swelling of feet and ankles Persistent itching Complications of CKD • • • • • • • • Kidney functions Calcium/Potassium/Sodium balance Acid excretion and phosphate excretion Erythropoiesis and RBC balance PTH and CKD retention and Hyperkalemia Anemia and acidosis Serum calcium and volume overload Calcitriol and water follows salt What CKD looks like under a microscope abnormal • DCT, PCT, Mesangium, Bowman's capsule, Glomerulus Normal • A Chronic glomerulonephritis • A Masson trichrome Normal Glomerulus preparation shows complete replacement of virtually all glomeruli by blue-staining collagen • Fibrosis is Scar tissue Kidney Function Tests • GFR, BUN (Blood Urea Nitrogen) tests, Creatinine • Pre-renal Azotemia, Renal, and Post-renal Glomerular Diseases • • • • Nephritic syndrome Nephrotic syndrome UTI, Cystitis, Pyelonephritis Renal cell cancer, Clear cell cancer, BPH Nephrotic Syndrome edema • Nephrotic syndrome results from increased glomerular basement membrane (GBM) permeability to serum proteins • In large part, nephrotic syndrome is mediated by damage to the glomerular podocyte • Massive proteinuria can cause urine to appear frothy, a clue to the presence of nephrotic syndrome Proteinuria 3.5 124h Nephritic Syndrome • Nephritic syndrome occurs as a result of inflammatory damage to the renal endothelium • Hematuria, Proteinuria (typically in the subnephrotic range), Rise in serum creatinine, Systemic hypertension • RBC casts are formed in tubular lumens in the kidney Differentiation Between Nephrotic Syndrome and Nephritic Syndrome • Nephrotic Syndrome - Proteinuria, Hematuria may/may not occur, Serum albumin low • Nephritic Syndrome - Hematuria and hypertension, Proteinuria < 3.5 g/24 hr, Noninflammatory renal damage Major Glomerular Diseases • • • • e Nephrotic Syndrome Nephritic Syndrome Minimal-change disease Post Streptococcal glomerulonephritis 7 I ii i i Causes of Glomerulonephritis: • • • • • • Focal segmental glomerulosclerosis Nephrotic IgA nephropathy Nephritic Membranous nephropathynephrotic Goodpasture syndrome Nephritic Membranoproliferative glomerulonephritis Post-Streptococcal Glomerulonephritis Nephritic Age prevalence: • Between 5 and 15 years; rare in children <2 years and uncommon in adults >40 years Cause of Post-Streptococcal Glomerulonephritis: • Group A Streptococcus (group A strep), which can cause throat and skin infections ladscan getkidneydamage Timeline: • Occurs 10 days after onset of strep throat symptoms • Takes 3 weeks after the start of group A strep skin infection for PSGN to develop Pathogenesis of PSGN: • • • • Deposition of antigen-antibody complex in glomerulus Increased production of epithelial cells lining the glomerulus Leukocytes infiltrate the glomerulus Thickening of the glomerular filtration membrane • Scarring and loss of glomerular filtration membrane • Decreased glomerular filtration rate (GFR) Signs and Symptoms: • • • • • • Hematuria (dark, reddish-brown urine or cola-colored urine) Hypertension Oliguria Proteinuria Edema Red blood cell casts in the urine Prognosis: • • • • 85 to 95% of patients retain or regain normal renal function over time Glomerular filtration rate (GFR) usually returns to normal in 1 to 3 months Proteinuria may persist for 6 to 12 months Microscopic hematuria may persist for several years Cause of cola-colored urine: • Hematuria Risk factors for UTI: • • • • • • Bladder incompetence Bladder tumors Decreased natural host defenses Ascending infection i Escherichiacoli Klebsiella Shortness of the female urethra Estrogen deficiency in postmenopausal women Cystitis • • • • Lutslowerurinarytractsymptoms Common symptoms include frequency, urgency, dysuria, and suprapubic pain Patients may also have foul-smelling urine and hematuria Diagnostic studies include microscopic urinalysis and urine culture Medical management typically involves antibiotics and patient education 6 Pyelonephritis UTI E coli orKlebsiella • Symptoms include fever, flank pain, abdominal pain, painful urination, and cloudy urine • Diagnostic studies include microscopic urinalysis and urine culture andmedicalmanagement • Management may involve antibiotics and supportive care Renal Cell Carcinoma • Clear cell carcinoma is the most common form of renal cell carcinoma neoplasticcellsappearvacuolatedormaybesolid • Common presenting symptoms include hematuria, flank pain, and a palpable mass • Treatment options include nephrectomy, partial nephrectomy, cryoablation, and radiofrequency ablation riskfactors cigarette chronickidneydiseasecadium cancer Benign Prostatic Hyperplasia (BPH) meme Pyg Train Petting state • BPH is characterized by the enlargement of the prostate gland • It can cause urinary symptoms such as increased frequency and urgency Prostate Cancer • Prostate cancer can present with urinary symptoms and may involve lymph nodes, seminal vesicles, and other nearby structures Benign Prostatic Hyperplasia (BPH) • BPH is an extremely common cause of prostatic enlargement • It is present in a significant number of men by 40 years of age and reaches a prevalence of 90% by the eighth decade • Common symptoms of BPH include hesitancy, poor stream, frequency, nocturia, urgency, and post-micturition dribbling Risk Factors for BPH • Non-modifiable risk factors include age, genetics, and testosterone levels • Modifiable risk factors include hormones (dihydrotestosterone and estrogen), metabolic syndrome, obesity, diabetes, diet, physical activity, and inflammation Pathogenesis of BPH 52 reductasetype2 d • Growth of stromal cells and proliferation of epithelial cells in the prostate glandular tissue • Androgen receptor, growth factors, and apoptosis play a role in the development of BPH Diagnosis of BPH • Diagnosis includes history, physical exam, ultrasound imaging of the kidneys and bladder, and measurement of post-void residual volume Prostate Disorders f Adenocarcinoma • Prostate cancer is the most common form of cancer in men, and African American men are 60% more likely to develop it compared to Caucasian or Hispanic men • Prostate cancer is the second leading cause of cancer death in American men, after lung cancer • About 1 in 41 men will die from prostate cancer Prostate Cancer Statistics • Prostate cancer accounts for 27% of cancer cases in the United States • It causes 10% of cancer deaths in the United States • 233,000 new cases of prostate cancer are diagnosed each year • The majority of prostate cancer cases are diagnosed in men aged 65 or older Other Leading Cancer Types • Other leading cancer types include lung, colon and rectum, urinary bladder, pancreas, melanoma of the skin, liver, kidney, leukemia, non-Hodgkin lymphoma, esophagus, oral cavity, and pharynx Family History • Family history of prostate cancer is a risk factor for developing the disease Prostate Cancer Statistics • In 2018, there were 323,630 cases of prostate cancer • Men with a blood relative (e.g., father or brother) who has had prostate cancer are twice as likely to develop the disease Risk Factors • • • • Age: risk increases with age Race: African American people have a greater risk of prostate cancer Family history: risk increases if a blood relative has been diagnosed with prostate cancer Obesity: obese individuals may have a higher risk of prostate cancer Progression of Prostate Cancer • • • • Androgens play a central role in prostate cancer progression Inflammation, senescence, and activation of developmental processes contribute to progression Oxidative/DNA damage signaling pathways, EMT, and telomere shortening are involved Prostatic adenocarcinoma can progress from normal prostate to intraepithelial neoplasia (PIN) to clinical adenocarcinoma Clinical Features • Prostate cancer may be asymptomatic and discovered through a needle biopsy or elevated PSA levels • It may cause irregular hard nodules in the bladder or obstruction in the urethra • Bone metastases, particularly in the axial skeleton, are common in advanced stages Limitations of Prostate-Specific Antigen (PSA) • PSA is not cancer-specific and can be elevated due to factors like BPH, prostatitis, or instrumentation of the prostate • Conversely, some patients with prostate cancer may have PSA levels below the cutoffs • PSA screening can lead to overdiagnosis and overtreatment of clinically insignificant cancers • Serial measurements of PSA are useful in assessing response to therapy Treatment of Prostate Cancer • Common treatments for localized prostate cancer are radical prostatectomy and radiotherapy • Advanced metastatic carcinoma is treated with androgen deprivation therapy • Reducing testosterone levels slows cancer growth or temporarily shrinks the cancer Introduction Heart failure, also known as congestive heart failure (CHF), is a progressive condition with a poor prognosis that affects over 5 million individuals in the United States alone. It can be categorized into systolic failure (decreased contractility), diastolic failure (decreased filling), or a mix of both. Leftsided cardiac failure is most commonly caused by ischemic heart disease, systemic hypertension, valve disease, or primary myocardial diseases, while right-sided cardiac failure is often associated with chronic lung disease or pulmonary hypertension. Diagnostic tests for heart failure include blood tests (BNP), electrocardiogram (ECG), echocardiogram, and chest X-ray. Anginais chestpainfromlackofoxygen Heart Failure Heart failure is often referred to as congestive heart failure (CHF) The common endpoint for many forms of cardiac disease A progressive condition with a poor prognosis Systolic failure - decrease contractility Diastolic failure - decrease filling Mixed Systolicstretchedheart Diastolic Decreasefiling Dense heart Right And Left Heart Failure • • • • • • • Heart failure can predominantly affect the left side of the heart, right side of the heart, or involve both sides Left Heart Failure PulmonaryEdema Ioxygen • The most common causes of left-sided cardiac failure are ischemic heart disease (IHD) due to coronary artery disease, systemic hypertension, mitral or aortic valve disease, and primary diseases of the myocardium • The morphologic and clinical effects of left-sided CHF stem from diminished systemic perfusion and elevated back pressures within the pulmonary circulation • Orthopnea: sensation of breathlessness in the recumbent position, relieved by sitting or standing • Paroxysmal nocturnal dyspnea (PND): sensation of shortness of breath that awakens the patient, often after 1 or 2 hours of sleep, usually relieved in the upright position Right-Sided Cardiac Failure Hepatomegaly Edema d00 • Associated with left-sided heart failure, chronic lung disease (pulmonary hypertension, COPD), coronary artery disease, and pulmonic stenosis Diagnosis- Heart Failure • Blood tests - BNP (Brain Natriuretic peptide) • Electrocardiogram (ECG) - records the electrical activity of the heart • Echocardiogram - uses sound waves to examine the heart • Chest X-ray - may show cardiomegaly and fluid in the lungs BNP Brain Natriuretic peptide • Stress on myocardium ➔ Increase BNP Diastolic dysfunction & Systolic dysfunction • Diastolic dysfunction refers to impaired relaxation of the heart during diastole, leading to decreased filling • Systolic dysfunction refers to impaired contraction of the heart during systole, leading to decreased pumping ability Right And Left Heart Failure • Right heart failure is a condition where the right side of the heart fails to effectively pump blood to the lungs • Left heart failure is a condition where the left side of the heart fails to effectively pump blood to the body Diagnosis- Heart Failure • Heart failure can be diagnosed through a medical evaluation that includes symptoms, physical examination, imaging tests, and measurement of cardiac biomarkers IHD Presentation • IHD, or Ischemic Heart Disease, can present with symptoms such as angina (chest pain) attackisnemesis heart Ml heart of musclecausebyacutethrombosis IHD Pathogenesis • IHD is caused by an imbalance between cardiac blood supply and myocardial oxygen and nutritional requirements, leading to myocardial ischemia Symptoms Of MI • In a myocardial infarction (MI), patients may experience substernal chest pain or discomfort, sweating, nausea or vomiting, light-headedness or fainting, breathlessness, feeling of "impending doom," severe anxiety or confusion Biomarkers Of IHD • Elevated troponin levels are common biomarkers observed in patients with IHD CLAM Types of Arrhythmias- Tachycardias • Tachycardias are a category of arrhythmias characterized by abnormally fast heart rates Types of Arrhythmias- Bradycardias • Bradycardias are a category of arrhythmias characterized by abnormally slow heart rates Regurgitation • Regurgitation refers to the backflow of blood through a defective heart valve Stenosis • Stenosis refers to the narrowing of a heart valve, restricting blood flow Bicuspid Aortic Valve • A bicuspid aortic valve is a congenital abnormality where the aortic valve has two leaflets instead of the normal three Cardiac Valvular Lesions • Cardiac valvular lesions refer to abnormalities or diseases affecting the heart valves Criteria • Criteria are specific measurements or characteristics used to diagnose or define a condition or disease Rheumatic Fever-Treatment • Treatment for rheumatic fever may involve antibiotics to eradicate the causative bacteria, antiinflammatory medications, and measures to manage symptoms and complications Bacterial Endocarditis • Bacterial endocarditis is an infection of the inner lining of the heart chambers and heart valves Why Is It Hard To Treat? • Bacterial endocarditis can be difficult to treat due to the strong adherence of bacteria to heart tissues, presence of biofilms, and potential for antibiotic resistance Symptoms Of Infective Endocarditis • Symptoms of infective endocarditis may include fever, fatigue, heart murmurs, embolic phenomena, and various systemic manifestations Eye in IE • Eye findings can sometimes be observed in patients with infective endocarditis, such as Roth's spots (retinal hemorrhages with pale centers) and Janeway lesions (red, non-tender spots on the palms and soles) Ischemic Heart Disease IHD • Ischemic heart disease (IHD) is caused by myocardial ischemia—an imbalance between cardiac blood supply (perfusion) and myocardial oxygen and nutritional requirements Coronary Artery Disease or IHD • Coronary artery disease, also known as IHD, refers to the narrowing or blockage of the coronary arteries that supply blood to the heart muscle • Common manifestations include angina and myocardial infarction (MI) IHD Presentation • In IHD, presentations can include angina pectoris (chest pain) due to transient, reversible myocardial ischemia • In the case of myocardial infarction (MI), there is cardiomyocyte death resulting from severe or prolonged ischemia IHD Pathogenesis • IHD development involves the progression of atheromatous plaques in coronary arteries, leading to acute coronary syndromes, such as MI Myocardial Ischemia • Myocardial ischemia leads to loss of myocyte function within minutes and can cause cell death within 30-40 minutes • Coagulative necrosis, characterized by preservation of tissue architecture, is typical in infarcts • Diagnosis of myocardial infarction is made based on symptoms, electrocardiographic changes, and measurement of cardiac-specific biomarkers like troponins Treatment Thrombolytics or "clot-busting" drugs and stent placement are treatment options for myocardial infarction Abnormal values associated with cardiac-related chest pain include elevated troponin levels Angina is chest pain from lack of oxygen Ischemic heart disease (IHD) refers to narrowed cardiac arteries leading to decreased blood supply to the heart Chest pain relieved with rest in a patient with ongoing tobacco abuse could potentially be due to angina Arrhythmias • Arrhythmias are abnormal heartbeats • The heart can beat too slowly, too quickly, or irregularly Types of Arrhythmias- Tachycardias • Tachycardias are characterized by an abnormally rapid heartbeat • Supraventricular tachycardias start in the upper chambers of the heart • Ventricular tachycardias start in the lower chambers of the heart Types of Arrhythmias- Bradycardias • Bradycardias are characterized by an abnormally slow heartbeat • Can be caused by sinus node dysfunction or heart block Diagnosis and Treatment Idina EFF • Diagnosis can be done through ECG/EKG or holter monitoring • Treatment can include medications (anti-arrhythmic) or pacemakers Atrial Fibrillation • Abnormal rhythm of the heart Cardiac Valvular Lesions • Valvular heart disease is when any valve in the heart is damaged or diseased • Regurgitation occurs when valves don't completely close, causing blood to leak back into the chamber • Stenosis occurs when the opening of the valve is narrowed and stiff, making it difficult for blood to pass through Bicuspid Aortic Valve Bicuspid Aortic Valve • • • • • The most common congenital valvular lesion is a bicuspid aortic valve Only two functional cusps instead of the normal three Occurs in 1% to 2% of all live births Bicuspid aortic valves are generally neither stenotic nor incompetent through early life They are more prone to early and progressive degenerative calcification that gives rise to stenosis Consequences of Bicuspid Aortic Valve • Narrowing of the aortic valve (aortic valve stenosis) • Backward flow of blood (aortic valve regurgitation) Treatment • Treatment depends on the extent of heart valve disease • There are no medications to treat a bicuspid heart valve • Surgery (aortic valve replacement) may be necessary Rheumatic Fever causedbymolecularmimicry Streptococcusbacteria • Rheumatic fever is an inflammatory disease caused by an untreated strep throat or scarlet fever • Usually affects children between 5 and 15 years old • Can cause permanent damage to the heart, including damaged heart valves and heart failure Rheumatic Fever Symptoms and Treatment JONES • Symptoms may include Sydenham chorea (involuntary movements) and erythema marginatum (skin rash) • Treatment includes antibiotics to eliminate strep bacteria and anti-inflammatory medications to reduce inflammation andanticonvulsantmedications • Preventive antibiotic treatment may be advised for those with a history of heart inflammation Bacterial Endocarditis • Endocarditis is a life-threatening infection of the heart lining and valves • Symptoms include fever and fatigue • Treatment is challenging due to the difficulty of eradicating the infection from heart tissues Infective Endocarditis • Inflammation of the heart involving the endocardium and the valves • Endothelial lining of the myocardium and heart valves is naturally resistant to infection • Injury to the lining increases adherence of platelets and fibrin, providing a site for bacteria to adhere • Bacteria enter the bloodstream from another infection • Bacteria attach to the damaged endothelium, grow, activate the coagulation system, and form vegetations • Bacteria cause invasive infection by adhering to the damaged or inflamed valves • Inability of antibiotics to penetrate vegetations makes treatment difficult • High density of bacteria within vegetations raises the risk of antibiotic-resistant subpopulations emerging • Valve damage is irreversible Symptoms of Infective Endocarditis • • • • • • • Fever, chills Tachycardia Fatigue, night sweats Aching joints and muscles Anorexia and weight loss Vascular phenomena Immunologic phenomena Eye in Infective Endocarditis • Conjunctivitis and Roth Spots Sepsis • Conjunctivitis: Vascular Phenomena resulting from septic emboli reaching the conjunctiva • Roth Spots: Immunologic Phenomena characterized by edematous and hemorrhagic lesions of the retina • Retinal capillary rupture and intraretinal hemorrhage cause white-centered retinal hemorrhage • Clotting cascade activation and formation of platelet-fibrin thrombi contribute to the formation of Roth Spots Introduction This text provides an overview of the pathology of the respiratory system, with a focus on lung diseases such as tuberculosis, pneumonia, and lung abscess. It also discusses obstructive lung diseases, including asthma, chronic bronchitis, and emphysema, and the pathogenesis and clinical manifestations of these conditions. Additionally, it touches on chronic obstructive pulmonary disease (COPD) and its association with cigarette smoking. Lung Pathology • • • • Primary respiratory infections are common Almost all forms of terminal disease involve the lungs Lung cancer is the most common malignancy in the U.S. Tuberculosis, pneumonia, and influenza are examples of respiratory infections Microscopic structure of the alveolar wall • Alveolar surface comprises 95% of the total surface area • Alveolar cells produce surfactant and repair the basement membrane • Macrophages, also known as dust cells, are present in the alveolar wall Gross pathology - normal lung • Hilar lymph nodes are found in a normal lung Aspiration • • • • Introducing anaerobic bacteria from the oral cavity can lead to lung abscess Lung abscesses are characterized by suppuration and necrosis Bacteria from the oral cavity are isolated from 60% of lung abscesses Lung abscesses are more common on the right side Obstructive and Restrictive Lung Diseases • Obstructive Lung Diseases include asthma, chronic bronchitis, and emphysema • Limitation of airflow is due to increased airway resistance or obstruction Chronic Obstructive Pulmonary Disease (COPD) • Causes irreversible airflow obstruction • COPD includes emphysema and chronic bronchitis • Cigarette smoking is the leading cause of COPD Asthma • Episodic, reversible bronchospasm caused by bronchoconstrictor response to stimuli • Affects 5% of adults and 7-10% of children • Extrinsic asthma is a hypersensitivity reaction to an allergen • Intrinsic asthma is triggered by non-immune mechanisms Emphysema • Abnormal permanent enlargement of airspaces distal to terminal bronchiole • Caused by protease/antiprotease imbalance and chemoattractant properties of nicotine Chronic bronchitis • Clinically defined as persistent cough with sputum production for at least 3 months in 2 consecutive years • Hypersecretion of mucus triggered by irritants and primarily affects large airways Pulmonary Hypertension and Cardiac Failure • These conditions can be caused by lung disease or other factors • Pulmonary hypertension is high blood pressure in the arteries of the lungs • Cardiac failure refers to the heart's inability to pump blood effectively Emphysema and Chronic Bronchitis • These two conditions often overlap in chronic obstructive pulmonary disease (COPD) • In COPD with predominant emphysema ("pink puffer"), symptoms include barrel-chest, weight loss, and prolonged expiration • In COPD with predominant chronic bronchitis ("blue bloater"), symptoms include obesity, history of infections with purulent sputum, and less prominent dyspnea • Chronic bronchitis is associated with hypercapnia, hypoxemia, and cyanosis How to remember the predominant disease: • Emphysema has the letter P, so it is associated with Pink Puffer • Chronic bronchitis has the letter B, so it is associated with Blue Bloater Restrictive Lung Diseases • Restrictive lung diseases are characterized by reduced expansion of lung parenchyma and decreased total lung capacity • These diseases can be caused by factors such as severe obesity, kyphoscoliosis, neuromuscular disorders, and certain lung diseases • Examples of restrictive lung diseases include pneumoconioses, acute respiratory distress syndrome (ARDS), and sarcoidosis Acute Respiratory Distress Syndrome (ARDS) • ARDS is a condition that starts as acute lung injury and progresses to respiratory failure • It is the most common cause of noncardiogenic pulmonary edema • ARDS can be caused by direct injury to the lung or indirect injury in the setting of a systemic process • Various conditions can be associated with ARDS development, including infection, physical/injury trauma, inhaled irritants, hematologic conditions, cardiopulmonary bypass, and hypersensitivity reactions ARDS Pathogenesis • ARDS is associated with a decrease in surfactant production • Histologically, alveolar walls are lined with hyaline and fibrin-rich material, with interstitial inflammation ARDS Clinical Presentation • Key symptoms include rapid onset of dyspnea, tachypnea, use of accessory respiratory muscles, hypoxemia, cyanosis, and bilateral opacities in radiograph • ARDS carries a mortality rate of 30-40%, which can be worse if due to septic shock • If a patient survives, it may take 6-12 months to return to normal respiratory function Respiratory Distress Syndrome in the Newborn • Respiratory distress syndrome in newborns is characterized by hyaline membranes and interstitial congestion • The problem is a lack of surfactant Sarcoidosis • Sarcoidosis is a multisystemic disease of unknown etiology • It appears to be an autoimmune disorder characterized by noncaseating granulomas in various tissues and organs • Diagnosis is made by excluding other diseases, as there is no definitive test • Sarcoidosis is more prevalent in certain populations, such as Danish, Swedish, and US black populations, and nonsmokers • In sarcoidosis, the lungs are involved in 90% of patients and present with symptoms of shortness of breath, dry cough, and substernal discomfort The Pneumoconioses • Pneumoconioses are a group of diseases caused by the inhalation of dust or other particulate matter • These diseases can result in fibrosis and scarring of the lung tissue Pneumoconiosis development is influenced by: • The type of particle and its ability to stimulate fibrosis • Dose and duration of the exposure • Size and shape of the particles • Additional effects of other irritants (e.g., smoking) Pathogenesis of the pneumoconioses: • Example: Macrophages ingest asbestosis and it can lead to fibrosis Asbestosis: • Incited by a family of crystalline hydrated silicates that are either serpentine (curly and flexible) or amphibole (straight and brittle) in shape • The latter are less common but more pathogenic (associated with mesotheliomas) Asbestosis pathology: • Diffuse pulmonary interstitial fibrosis containing asbestos bodies (asbestos fibers coated with iron-containing protein called ferritin); most severe in lower lobes • Lungs develop honeycombed appearance as fibrosis involves alveolar sacs and alveoli • Pleural plaques; occur most frequently on the anterior and posterolateral aspects of the parietal pleura and over the diaphragm • Pleural effusions (uncommon) and visceral pleural fibrosis (rare) Ferruginous bodies (aka asbestos bodies) - Picture Pleural plaques - Picture Asbestosis Clinical Course: • Typically develops 10-20 years after exposure • Dyspnea, later accompanied with productive cough – may be extent of symptoms for life • Respiratory failure à right-sided heart failure à death Asbestos exposure is associated with an increased risk of cancer: • Bronchogenic carcinoma - risk increased 5x in asbestos-exposed, synergistic effect of smoking and exposure = risk 50x • Pleural and peritoneal mesothelioma - rare, highly malignant neoplasm (poor prognosis), 90% of cases associated with asbestos exposure, risk increased 1000x in asbestos-exposed (no increased risk for smokers), symptoms: pleural effusions, dyspnea, chest pain • Increased risk of laryngeal, stomach, and colon cancers Coal Workers’ Pneumoconiosis (CWP): • Asymptomatic anthracosis - carbon pigment accumulation in macrophages along pleural lymphatics, asymptomatic, patients: typically coal miners, but also seen in city dwellers and smokers of tobacco, marijuana, crack cocaine, etc. • Simple CWP (black lung disease) - coal macules (carbon-laden macrophages) and coal nodules (+collagen) in the upper lobes, little pulmonary dysfunction • Complicated CWP (“genuine” black lung disease) - advanced stage of CWP present in ~10% of patients, involves Progressive Massive Fibrosis (PMF) -- many large nodules and/or one or more circumscribed areas of dense black scar-like tissue up to 10 cm in diameter, lung function compromised leading to respiratory distress, pulmonary hypertension and right-sided heart failure Complicated CWP - "genuine" black lung disease, coal dust is not carcinogenic, no association with lung cancer Silicosis: • Lung disease caused by inhalation of crystalline forms of silica (quartz, cystobalite, etc) • According to your text, it is the most prevalent chronic occupational disease in the world • Patients: sandblasters, metal grinders, miners, exposure to plume from volcanic eruptions Silicosis Pathology: • Dense, nodular fibrosis of the upper lobes • Hard, collagenous scars; eggshell calcification more uncommon • May develop PMF Silicosis Clinical Course: • Asymptomatic, progressing to dyspnea • Increased risk of tuberculosis Hypersensitivity pneumonitis: • Immunological lung disease caused by the inhalation of organic dust and occupational antigens (moldy hay, bird droppings, etc) • Differs from asthma in that it involves alveoli (syn. "allergic alveolitis") instead of bronchi and bronchioles • Diagnostic immunology important – identify antigen so exposure can be prevented Clinical course of hypersensitivity pneumonitis: • Fever, dyspnea, cough, leukocytosis • Diffuse and nodular infiltrates • Decrease in lung capacity Pulmonary Infections: Compliance • Exposure to antigen can lead to chronic fibrotic lung disease Pulmonary Infections: RTIs and Pneumonia • RTIs cause the largest number of workdays lost • Pneumonia is responsible for 1/6th of U.S. deaths • Resistance to infections is influenced by various factors such as cough reflex, mucociliary apparatus, alveolar macrophages, pulmonary congestion and edema, accumulation of secretions, and decreased host resistance Pulmonary Infections: Important Points • One type of pneumonia can predispose to another (viral influenza can lead to bacterial pneumonia) • Distinguishing between secondary and primary pneumonia can be challenging • Patients with chronic diseases are prone to acquiring pneumonia while in the hospital (nosocomial pneumonia) Community-Acquired Acute Pneumonias • • • • • Bacterial or viral pneumonia Streptococcus pneumoniae is the most common cause Usually follows upper respiratory tract infections Bacteria invade lung parenchyma, leading to inflammatory exudate and consolidation Predisposing conditions include age, chronic diseases (COPD, diabetes, congestive heart failure), immune deficiencies, and decreased splenic function Community-Acquired Atypical Pneumonia • Characterized by a different clinical course compared to acute pneumonia • Causal organisms include Mycoplasma pneumoniae, influenza viruses A and B, respiratory syncytial viruses (RSV), cytomegalovirus, adenovirus, and rhinoviruses • Typical symptoms may include moderate sputum, no consolidation, moderate WBC count elevation, and alveolar exudates lacking • Low mortality rate, except for antigenic shifts that occur in influenza pandemics Nosocomial Pneumonia • Pulmonary infection acquired during a hospital stay • High-risk individuals include patients on mechanical ventilation and those who are immunosuppressed • Causal organisms include Staphylococcus aureus and Gram-negative rods (Enterobacteria and Pseudomonas sp.) Tuberculosis • Mycobacterium tuberculosis is responsible for most cases • Reservoir is other humans with active TB and it is transmitted through acid-fast bacilli • High-risk individuals include the elderly and urban poor Primary Tuberculosis • Mostly asymptomatic or flu-like symptoms • • • • Gohn focus: small, tan-yellow granuloma May progress to lymphatics (Gohn complex) In most people, it will not progress further May decrease in size and calcify Primary Tuberculosis: Pathogenesis • Infection, not disease • Lasts decades TB granuloma features • Epithelioid cells: flattened macrophages • Giant cells with nuclei in a horseshoe-shaped pattern Progressive Primary Tuberculosis • • • • • • Only 5% of newly infected people develop significant disease Resembles acute bacterial pneumonia Lobe consolidation Hilar adenopathy Pleural effusion Lymphohematogenous dissemination may occur (meningitis, miliary TB) Secondary Tuberculosis • • • • • • Usually arises from reactivation of dormant primary lesion Classically localized to apex of upper lobes Cavitation common, mycobacteria disseminates to airways, sputum, another host Systemic symptoms: malaise, anorexia, low-grade fever, night sweats Sputum: mucoid to purulent to hemoptysis (50%) Pleuritic pain common Miliary Tuberculosis • Lung neoplasms Lung cancer mortality ratio distribution in the U.S. • More common in males • More common in smokers • Small cell lung cancer, non-small cell lung cancer Squamous Cell Carcinoma • Most common in male smokers • Mostly arises centrally (1st, 2nd, 3rd bronchi) • Firm with pale tan to white cut surface • Tendency to cavitate • Metastasizes late Adenocarcinoma • • • • Most common in non-smoking women Tends to occur more peripherally in the lung Slow growth, but earlier metastasis than other non-small cell carcinomas ~80% produce mucin (Trousseau's syndrome) Bronchioalveolar Carcinoma • Subtype of Adenocarcinoma • Columnar/cuboidal cells proliferate along the framework of alveolar septae • Cells are well-differentiated Large Cell Carcinoma • Tumors begin anywhere in the lungs and tend to grow quickly • Anaplasia with prominent nuclei and nucleoli Small Cell Carcinoma • • • • • • Strongest association with smoking Occur in major bronchi and lung periphery Highly malignant Tendency to spread along the bronchi May secrete polypeptide hormones (ADH, ACTH) Microscopic pattern: basophilic cells Lung Carcinomas: Clinical course • • • • Usually discovered when patients are in their 50s Major complaints: cough, weight loss, chest pain, dyspnea 5-year survival rate is approximately 15% Adenocarcinoma and squamous cell have a better prognosis Head and Neck Disorders • Acute Otitis Media • Vertigo • Sinusitis Orbital Cellulitis • May result from sinusitis, commonly from ethmoid sinusitis • Thin lamina papyracea can contribute to its occurrence Allergic Rhinitis • Symptoms include runny nose, sneezing, conjunctival hyperemia, and watery eyes • Not sight-threatening Pharyngitis • Common symptoms include enlarged cervical nodes, sore throat, and fever • Can be viral or bacterial Salivary Gland Tumors • 80% of tumors involve the parotid gland • Non-painful swelling • Tumors can be benign or cancerous Temporomandibular Joint Disorder • Symptoms include headaches, facial pain, and jaw pain • Multiple causes such as chronic inflammation, trauma, developmental anomalies, etc. • Jaw may "pop" when chewing or "lock" if opening wide Introduction This text provides learning objectives for understanding various endocrine and metabolic system disorders such as diabetes mellitus, diabetes insipidus, hypothyroidism, hyperthyroidism, Addison's disease, Cushing syndrome, and pheochromocytoma. It discusses the pathophysiology and clinical manifestations of these conditions, as well as the role of hormones like insulin, parathyroid hormone, and anti-diuretic hormone. It also differentiates between type 1 and type 2 diabetes mellitus based on their pathogenesis and onset. Learning Objectives • Compare and contrast the pathophysiology of type 1 and type 2 diabetes mellitus regarding the pathogenesis, typical age of onset, and the role of insulin • Understand the pathophysiology of diabetes insipidus and its clinical manifestation • Define hypothyroidism and hyperthyroidism and list the common causes of these • Discuss the role of parathyroid hormone and list the consequences of hyperparathyroidism and hypoparathyroidism • Define Addison’s disease and its clinical consequences • Describe Cushing syndrome • Describe the pathogenesis of pheochromocytoma and its presentation Parathyroid Hormone • The function of Parathyroid Hormone (PTH) • Hyperparathyroidism • Hypoparathyroidism Adrenals • Cushing Syndrome • Adrenal Insufficiency • Adrenal Medulla The Pituitary Gland • • • • The Hypothalamic Pituitary axis Anti-Diuretic Hormone (ADH) and Diabetes Insipidus Prolactinoma Growth Hormone Thyroid Disorders • Hypothyroidism vs Hyperthyroidism • Chronic Lymphocytic (Hashimoto) Thyroiditis (Hypothyroidism) • Graves disease (Hyperthyroidism) Diabetes Mellitus • Type 1 Diabetes • Type 2 Diabetes • Type 1 vs Type 2DM The Islet of Langerhans Pancreas • 70-80% insulin, glucagon, BIn, SaD Metabolic Actions Of Insulin Classification of Diabetes Mellitus • Type 1: ∼ 5% of all patients with diabetes, childhood onset, highest prevalence in nonHispanic whites • Type 2: estimated prevalence in the US is 9.3%, adult onset, highest prevalence in Hispanics, Native Americans, Asian Americans, African Americans Normal blood glucose: 70 to 120 mg/dL, target HbA1c level in diabetics: 7% to 8% Type 1 Diabetes I • Autoimmune disease, genetic susceptibility & environmental trigger -> autoimmune destruction of beta cells • Production of autoantibodies targeting beta cells -> progressive destruction of beta cells -> absolute insulin deficiency -> hyperglycemia and DM • Associated with other autoimmune conditions like Hashimoto thyroiditis and celiac disease Type 2 DM • Decreased ability of peripheral tissues to respond to insulin (insulin resistance) and beta cell dysfunction leading to inadequate insulin secretion • Strong genetic association, polyuria, polydipsia, polyphagia Primary pathological mechanism underlying type 1 diabetes: Autoimmune destruction of pancreatic beta cells Pathology of Type 1 DM: Autoimmune "insulitis" with T lymphocytes infiltration and beta cell depletion a GAD Pathology of Type 2 DM: Amyloid deposition in the islets, insulin resistance, and beta cell failure Type 1 diabetes • • • • • • Mostly affects children/teens Usually normal or thin Lack of insulin 5%-10% of cases Age of onset: usually between 5 and 25 Treatment: insulin injections, dietary plan, regular check-ups, daily exercise eyeexams start 5years afterdiagnosis • Progression: rapid, within weeks Type 2 diabetes • • • • • • • • • Insulin resistance causes less sugar to be removed from the blood Causes: genetic factors, obesity (central adipose), physical inactivity No HLA association Mostly affects adults, elderly, certain ethnic groups Mostly overweight or obese 90%-95% of cases Age of onset: usually over 40 Treatment: diet, exercise, weight loss, medication, insulin injections if needed Progression: slow, over years eyeexams startattime of diagnosis Differences between type 1 and type 2 diabetes: • • • • Type 1: autoimmune destruction of pancreatic beta cells, leading to absolute insulin deficiency Type 2: pancreatic beta cells function normally initially, but develop insulin resistance Obesity is more common in type 2 diabetes Type 2 diabetes typically presents at a younger age compared to type 1 diabetes Recommendation for Bella: mostcommoncauseofvisuaimpairment • Continue seeing the eye doctor once a year Pathophysiology of diabetic retinopathy: Pericyte loss leads to weakened capillaries and microaneurysms Weakened blood vessels rupture, causing dot/blot hemorrhages Leakage of plasma proteins from damaged vessels results in hard exudates Decreased blood supply causes areas of ischemia, cotton wool spots (soft exudates) Retinal ischemia upregulates VEGF, leading to irregular neovascularization and fibrosis retinaltraction Proliferative retinopathy: rapid progression with potential blindness, vitreous hemorrhage, and retinal detachment • Macular edema: retinal thickening and edema involving the macula • • • • • • manifestations cataractformation Glaucoma Fundus examination findings related to diabetic changes: • C. Retinal hemorrhages Earliest manifestation of diabetic retinopathy: non proliferative • Microaneurysms (red dots) Egan HIYA Role of Vascular Endothelial Growth Factor (VEGF) in eye vascularization and diseases: • VEGF promotes the growth of blood vessels in the eye • It inhibits abnormal blood vessel growth in the eye neo • VEGF is not associated only with non-vascular eye diseases • VEGF has an impact on eye vascularization The Pituitary Gland: • • • • Disruption of the hypothalamic-pituitary axis can occur in primary, secondary, or tertiary forms Primary disruptions involve disorders of the peripheral endocrine gland Secondary disruptions involve pituitary dysfunctions Tertiary disruptions involve hypothalamic disorders Anti-Diuretic Hormone (ADH): Tasopressin • ADH stands for Anti-Diuretic Hormone • ADH helps in reabsorbing water in the kidneys • Dehydration causes the release of ADH, leading to increased water reabsorption by the kidneys Diabetes Insipidus (DI): • DI is characterized by excessive thirst and frequent urination due to inadequate ADH production or response • Different causes of DI include head trauma, tumors, surgical procedures, etc. • Manifestations of DI include large volumes of dilute urine, increased serum sodium, and increased thirst Hypothalamic-Pituitary Axis: • The hypothalamus regulates hormone secretion from the anterior pituitary gland • Stimulatory hormones released by the hypothalamus include CRH, GHRH, GnRH, and TRH • Inhibitory factors released by the hypothalamus include GIH (or somatostatin) and PIF (or dopamine) • The release of hormones from the anterior pituitary are modulated by these stimulatory and inhibitory factors Anterior Pituitary Disease: • Hyperpituitarism is usually caused by adenomas • Hypopituitarism may result from ischemic injury, surgery, radiation, or inflammatory reactions • Local mass effects of non-functional pituitary adenomas can cause hypopituitarism, visual field defects, and elevated intracranial pressure Pituitary Cell Types: Prolactinoma • Lactotrophs are the most common hyperfunctioning pituitary adenomas, causing high levels of prolactin and affecting females with galactorrhea and amenorrhea • Somatotrophs are the second most common hyperfunctioning pituitary adenomas, causing excessive growth hormone (GH) levels and leading to gigantism or acromegaly Normal Growth Hormone Function: • Growth hormone (GH) excess before the epiphyses close causes gigantism • Growth hormone (GH) excess after the epiphyses close causes acromegaly