Focused Review Exam 3 Summer 2024 (1).docx

**Summer 2024 Exam 3 Adv Pathophysiology** **NOTE: I include MOST of these concepts in the Kaltura voiceovers housed in the announcements of your canvas course but may not touch on some if fairly straight forward. [However, review ALL of these concepts.] -- *PLEASE REACH OUT TO YOUR COURSE FACULTY...

**Summer 2024 Exam 3 Adv Pathophysiology** **NOTE: I include MOST of these concepts in the Kaltura voiceovers housed in the announcements of your canvas course but may not touch on some if fairly straight forward. [However, review ALL of these concepts.] -- *PLEASE REACH OUT TO YOUR COURSE FACULTY IF YOU HAVE ANY QUESTIONS!!!* This exam covers weeks 8, 9, 10, and 11 content.** ***[Exam 3 Part 1]*** ***[Alterations of the Pulmonary System]*** **[Obstructive pulmonary diseases:] These disorders are characterized by infiltration of the lung by inflammatory cells with the release of numerous cytokines (Interleukins are a group of cytokines that are usually pro-inflammatory) that contribute to airway damage and mucus production. Airway obstruction is worse with expiration. More force (i.e., use of accessory muscles of expiration) or more time is required to expire a given volume of air, and emptying of the lungs is slowed causing AIR-TRAPPING thus increased residual volume. Individuals have an increased work of breathing with subsequent dyspnea, hypoxia, and hypercapnia. The most common obstructive diseases are asthma and chronic obstructive pulmonary disease (COPD) (chronic bronchitis and emphysema).** ***Asthma*. Most common phenotype is allergic asthma. This is a Type I hypersensitivity reaction.** ***Chronic Bronchitis* *is defined as hypersecretion of mucus and chronic productive cough that continues for at least 3 months of the year (usually the winter months) for at least 2 consecutive years.* Continual bronchial inflammation causes bronchial edema and increases the size and number of mucous glands and goblet cells in the airway epithelium. Thick, tenacious mucus is produced and cannot be cleared because of impaired ciliary function. The lung's defense mechanisms are, therefore, compromised, increasing susceptibility to pulmonary infection, which contributes to airway injury. Hypercapnia (increase in P~a~CO~2~) related to chronic hypoventilation is common.** ***Emphysema* is characterized by destruction of alveoli walls through the breakdown of elastin within the septa. This destruction of alveoli walls causes abnormal permanent enlargement of the air spaces in the lungs, also known as gas-exchange acini. Expiration becomes difficult because loss of elastic recoil reduces the volume of air that can be expired passively, and air is trapped in the lungs. Air trapping causes hyperexpansion of the chest (barrel chest), which puts the muscles of respiration at a mechanical disadvantage. Smoking is a common cause of emphysema; however, α~1~-Antitrypsin deficiency is suggested in nonsmokers and individuals who develop emphysema before age 40 years.** ***Cor pulmonale*: It is associated with pulmonary disorders. Caused by hypoxemia and hypercapnia that leads to pulmonary vasoconstriction and increased pressures in the pulmonary system. As increased pulmonary arterial pressure causes increased workload on the right ventricle Cor pulmonale develops -- as it progresses further hypertrophy and dilation of the right ventricle eventually leads to right-sided heart failure.** **[Restrictive Lung Diseases:] Decreased compliance (stiffness) meaning it takes more effort to expand the lungs during *inspiration*. Examples are aspiration, pulmonary edema, acute respiratory distress syndrome (ARDS), and pneumoconiosis.** ***Pneumoconiosis, a restrictive lung disease,* represents any change in the lung caused by inhalation of inorganic dust particles, which usually occurs in the workplace. The dusts of silica (silicosis), asbestos (asbestosis), and coal (black lung) are the most common causes of pneumoconiosis. *It is NOT reversible, and treatment is usually palliative and focuses on preventing further exposure.*** ***[Respiratory Tract Infections]*** ***Pneumonia*** **Accounts for about 45,000 deaths per year in the United States.** **The nasopharynx and oropharynx constitute the first line of defense for most infectious agents. However, risk factors such as age (below the age of 5 and over the age of 70), compromised immunity, underlying lung disease, malnutrition, alcoholism, living in nursing homes or extended care facilities.** ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ***Empyema. A type of pleural effusion containing infectious organisms. Usually, a complication of pneumonia in the elderly and young children. Pulmonary lymphatics are blocked, leading to an outpouring of contaminated lymphatic fluid into the pleural space.*** ***[Pulmonary Vascular Disease]*** ***Pulmonary Emboli (PE): The first symptom in 25% of people with PE is death. Most common cause: Deep Vein Thrombosis (DVT) develops, embolus breaks off and travels through the circulation to a pulmonary vessel. Risk factors, referred to as the triad of Virchow, are: venous stasis (immobility), injury to epithelial cells that line the vessels (trauma, infection such as COVID-19), and hypercoagulability (malignancy).*** **[Malignancies of the Respiratory Tract]** ------------------------------------------------------- **Lung Cancer -- Two main categories:** --------------------------------------- ***Non--Small Cell Lung Cancer (NSCLC) Squamous cell carcinoma:* Tumors are typically located centrally near the hila and project into bronchi. Because of this central location, nonproductive cough or hemoptysis is common. Chest pain is a late symptom associated with large tumors. *These tumors can remain fairly well localized and tend not to metastasize until late in the course of the disease. The other two types, Adenocarcinoma and Large cell carcinoma tend to metastasize more quickly. [ ]*** ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- **[Alterations of the Pulmonary System in Children:]** ***Pediatric obstructive apnea syndrome (OSAS)* Results from partial or complete upper airway obstruction during sleep. The incidence is higher among obese children. Airway narrowing is caused from craniofacial abnormalities (low mandibular plane angle), obesity (increases airway collapsibility), asthma, allergies, adeno-tonsillar hypertrophy. Sleep patterns are affected and include snoring, labored breathing, oxygen desaturation with hypercapnia waking the child up, and the pattern repeats. Associated with cognitive and neurobehavioral impairment.** ***Surfactant Deficiency Disorder (SDD):* SDD, also known as respiratory distress syndrome, almost occurs exclusively in premature infants born before 28 weeks gestation. What does surfactant do? It produces a detergent-like effect that separates the liquid molecules in the alveoli to decrease alveolar surface tension. This expands the alveoli to facilitate gas exchange. Also, lungs in the premature infant are underdeveloped and have small alveoli adding to the difficulty of proper alveoli inflation.** ***Cystic Fibrosis*: Autosomal recessive disease with multiorgan involvement. It affects the lungs, digestive tract, and reproductive organs. Mutations of a gene, known as the cystic fibrosis transmembrane conduction regulator (CFTR), that causes abnormal expression of the CFTR protein. SO WHAT -- Without adequate CFTR function, chloride and water are not transported appropriately across epithelial membranes. This causes thick, dehydrated mucus. Mucous plugs, chronic inflammation and infection. (Respiratory failure is almost always the cause of death).** ***Bronchiolitis* -- most common viral respiratory tract infection of the small airways in children younger than 2 years of age. The most common pathogen is the respiratory syncytial virus (RSV). Premature infants are more susceptible to a severe or even a deadly course. Viral infections can cause necrosis of the bronchial epithelium and destruction of ciliated epithelial cells. Mucosa becomes edematous along with accumulation of mucus, and bronchospasms with narrowing of peripheral airways.** ***Sudden infant death syndrome* (SIDS) -- is the most common cause of sudden unexpected infant death. The etiology of SIDS remains unknown. Highest risk is from 2-4 months of age. However, risk factors associated with SIDS: low-birth weight, large family size, lower socioeconomic status, sleeping on soft bedding, parental smoking (see page 1207 for complete list). Education is key to prevention.** ***[Alterations of the Renal and Urinary Tract Systems]*** ***[Nephrolithiasis (Kidney Stones):] They can be located in the kidneys, ureters, and bladder. Stones are classified according to the primary minerals that make up the stone. However,* the most common type of kidney stone is Calcium oxalate. Pathophysiology: a) supersaturation of the mineral in the urine, b) grow through crystallization or agglomeration (aggregation), and c) lack of stone inhibitors (uromodulin).** **Microorganisms usually associated with acute pyelonephritis include E. coli, Proteus, or Pseudomonas. These microorganisms split urea into ammonia, making alkaline urine that increases the risk of stone formation.** ***[Glomerular Disorders]*** ***Acute Kidney Injury* (AKI) may be acute and rapidly progressive (within hours), and the process may be reversible. Renal insufficiency refers to a decline in renal function to about 25% of normal or an eGFR of 25 to 30 ml/minute. (eGFR is extremely useful in determining improvement or decline in kidney function). Levels of serum creatinine and urea are mildly elevated. However, changes in serum creatinine level occur only if more than 50% of glomerular filtration is lost. *Table 38.11 in textbook (modified:)*** **[Prerenal AKI:] Inadequate kidney perfusion is the most common reason for AKI.** - **Hypovolemia -- such as blood loss** - **Reduced cardiac output: heart failure with reduced ejection fraction** - **Systemic hypotension or hypoperfusion** - **Acute Myocardial Infarction** **[Intrarenal AKI:] *Disorders involving the renal parenchymal or interstitial tissue*** - **Renal artery stenosis** - **Renal vein thrombosis** - **Acute tubular necrosis (postischemic or nephrotoxic)** - **Glomerular: immune-complex diseases such as lupus nephritis** **[Postrenal AKI:]** **disorders associated with acute urinary tract obstruction** - **Bladder outlet: Benign prostatic hypertrophy** - **Ureteral obstruction destruction (tumors, stones, clots)** - **Neurogenic bladder** ***[Chronic Kidney Failure]* The factors that contribute to the pathogenesis of CKD are complex and involve the interaction of many cells, cytokines, and structural alterations. *Two factors that have consistently been recognized to advance renal disease are proteinuria and angiotensin II activity.* Glomerular capillary hypertension (causes damage allowing protein to escape into the urine) and hyperfiltration as well as increased glomerular capillary permeability lead to proteinuria. Proteinuria contributes to tubulointerstitial injury by accumulating in the interstitial space and activating complement proteins and other mediators and cells, such as macrophages, that promote inflammation and progressive fibrosis. Angiotensin II activity is also elevated with progressive nephron injury. Angiotensin II promotes glomerular hypertension and hyperfiltration caused by efferent arteriolar vasoconstriction and also promotes systemic hypertension.** **Systematic effects of CKD -- see table 38.16 (pg. 1261). You will see that no organ system is spared from progressive declining kidney function. Here are a few to focus on:** ***Hematologic*: The kidneys are the primary site of production for erythropoietin (EPO), a hormone that stimulates the bone marrow to produce red blood cells. Reduced erythropoietin secretion associated with CKD reduces red blood cell (RBC) production. NOTE: also, the uremic environment shortens the life span of the RBC.** ***Skeletal:* Hypocalcemia is accelerated by impaired renal synthesis of 1,25-dihydroxy-vitamin D. Renal phosphate excretion also diminished. Phosphate binds to calcium -- contributing further to hypocalcemia. (Hypocalcemia/hyperphosphatemia. Calcium-phosphate have a reciprocal relationship -- one goes up the other goes down.). Decreased calcium levels TRIGGERS: parathyroid to secrete PTH. COMBINED EFFECTS: secondary hyperparathyroidism and vitamin D deficiency cause renal osteodystrophy and increased risk of skeletal fractures.** **Acid-base balance: End-Stage Renal Failure (ESRF) Metabolic acidosis (Chapter 3) develops when GFR decreases to less than 20% to 25% of normal. The causes of acidosis are primarily related to decreased hydrogen ion elimination and decreased bicarbonate reabsorption*.* With ESRF, metabolic acidosis may be severe enough to require alkali therapy and dialysis. Bicarbonate levels should be maintained at about 22 mEq/L. Electrolyte Imbalance: With progression of ESRF total body potassium levels may become life threatening (Hyperkalemia).** **Alterations of Renal and Urinary Tract Function in Children: *Hypospadias* is the condition when the urethral meatus is located on the ventral portion or undersurface of the penis. Epispadias is characterized by the dorsal urethra has not fused and has failed to form a tube.** ***[Part 2 ]*** ***[Alterations in the Reproductive Systems and ]*** ***[Sexually Transmitted Infections]*** ***Alterations in the Female Reproductive System*** ***[Hormonal and Menstrual Alterations]*** ***Primary dysmenorrhea*** ***is attributed to excessive endometrial prostaglandin production.* Women with painful periods produce more prostaglandin, a potent myometrial stimulant and vasoconstrictor, as asymptomatic women. *Elevated levels of prostaglandins cause uterine hypercontractility, decreased blood flow to the uterus, and increased nerve hypersensitivity, thus resulting in pain.* Secondary dysmenorrhea results from disorders in the presence of pelvic pathologic conditions such as endometriosis (the most common cause), endometritis (infection), pelvic inflammatory disease, uterine fibroids (leiomyomas), polyps, tumors, ovarian cysts, or intrauterine devices (IUDs).** ***Polycystic Ovarian Syndrome (PCOS)*. Although the underlying cause of PCOS is unknown, a genetic basis is suspected. No single factor fully accounts for the abnormalities of PCOS and is a leading cause of infertility in the United States. Although PCOS presents in a variety of ways, it is defined as having at least two of the following three features: Irregular ovulation, elevated levels of androgens (e.g., testosterone), and the appearance of polycystic ovaries on ultrasound. Polycystic ovaries do not have to be present to diagnose PCOS, and conversely their presence alone does not establish the diagnosis. A hyperandrogenic state and ovulatory dysfunction are the cardinal features in the pathogenesis of PCOS. Excessive androgens affect follicular growth. Follicle-stimulating hormone (FSH) is decreased (note: FSH regulates the menstrual cycle and stimulates egg production in the ovaries).** ***G*lucose intolerance/insulin resistance (IR) often run parallel and markedly aggravate the hyperandrogenic state, thus contributing to the severity of signs and symptoms of PCOS. Obesity adds to and worsens IR.** **[Benign Growths and Proliferative Conditions]** ***Leiomyomas,* *commonly called myomas or uterine fibroids, are benign smooth muscle tumors in the myometrium. Leiomyomas are the most common benign tumors of the uterus*. Prevalence increases in women ages 30 to 50 but decreases with menopause. The cause of uterine leiomyomas is unknown, although their size appears to be related to estrogen and progesterone, growth factors, angiogenesis, and apoptosis.** **The formation and growth of uterine leiomyomas is not well understood; however, genetics, environmental factors, steroid hormones (estrogen and progesterone), and angiogenesis all play a role. Fibroid development begins with a single uterine smooth muscle cell (myometrium). Degeneration and necrosis may occur when the leiomyoma outgrows its blood supply, which is more common in larger tumors and is frequently accompanied by pain.** **The leiomyoma can make the uterine cavity larger, thereby increasing the endometrial surface area. This enlargement may account for the increased menstrual bleeding associated with leiomyomas. Although pain is not an early symptom, it occurs with the devascularization of larger leiomyomas and is associated with blood vessel compression that limits the blood supply to adjacent structures. Because the fibroid is relatively slow growing, enabling adjacent structures to adapt to pressure, symptoms of abdominal pressure develop slowly.** ***Benign Ovarian Cysts* -- Two types:** ***Follicular cysts*: Follicular cysts are filled with fluid and can be caused by a transient condition in which the dominant follicle fails to rupture or one or more of the nondominant follicles fail to regress.** ***Corpus luteum cyst*: may normally form by the granulosa cells left behind *after ovulation*.** **Rupture occasionally occurs and can *cause massive bleeding*, with excruciating pain; immediate surgery may be required.** ***Endometriosis* is the presence of functioning endometrial tissue or implants outside the uterus. Like normal endometrial tissue, the ectopic (out of place) endometrium responds to the hormonal fluctuations of the menstrual cycle. Common sites of implantation include the pelvic peritoneum, ovaries, and uterosacral ligaments. Implants can also be found outside the pelvic locations: GI tract, lungs, diaphragm, abdomen, pericardium. The exact cause of endometriosis is not known. The clinical manifestations of endometriosis can mimic other disease processes (i.e., PID, irritable bowel syndrome, ovarian cysts). Symptoms are variable in frequency and severity and most commonly include pain and infertility. Women with endometriosis report progressive dysmenorrhea, dysuria, and dyspareunia (pain on intercourse); they may also report constipation and abnormal vaginal bleeding. High risk for infertility and cancers, especially ovarian.** **[Infection and Inflammation]** ***Pelvic Inflammatory Disease* (PID)** **An acute inflammatory process caused by infection. Infection of the upper female genital tract leads to inflammatory damage, including scarring, adhesions, and partial or total obstruction of the fallopian tubes. Scarring increases the risk of a later ectopic pregnancy because the mobility of an egg through the fallopian tubes is slowed by damaged cilia. Loss of the ciliated epithelial cells along the fallopian tube lining results in impaired ovum transport and increases the risk for infertility and ectopic pregnancy.** **Scarring and adhesions also can result in chronic pelvic pain. Increased risk of uterine cancer** **Two sexually transmitted infectious causes of PID are gonorrhea and chlamydia.** **Bacterial vaginosis (BV) is a noninflammatory condition resulting from an overgrowth of anaerobic bacteria. The overgrowth causes a shift in the composition of the vaginal flora and produces a malodorous vaginal discharge. Pain and itching are common manifestations. *BV is present in up to 66% of women with PID.***