Revised Final Exam Worksheet PDF

REVISED FINAL EXAM WORKSHEET Make sure you understand the pathophysiology and clinical manifestations. Be able to compare and contrast. PP: Exam 3 Anemia of Chronic Disease EXAM 1...

REVISED FINAL EXAM WORKSHEET Make sure you understand the pathophysiology and clinical manifestations. Be able to compare and contrast. PP: Exam 3 Anemia of Chronic Disease EXAM 1 Cellular function and Cellular Responses 1. Types of Necrosis Differentiate the different types of necrosis. Coagulative Necrosis- The dead cells are preserved for a few days. The injury denatures the structural cell proteins and enzymes blocking proteolysis from happening. Eventually contents are removed via phagocytosis but leaves coagulative remnants. Ischemia causes this type of necrosis in all organs except for the brain. ○ Example: Infarct Liquefactive Necrosis- digestions of dead cells resulting in a transformation of the tissue into a viscous liquid. This liquid contains leukocytes and is termed pus. For unknown reasons an infarct/ischemic event in the brain (and CNS) causes this type of necrosis. ○ Example: Ischemic CVA Fat Necrosis- Refers to focal areas of fat destruction. Normally resulted from pancreatic enzyme release into the peritoneal cavity causing pancreatitis (but in lecture she referred to breast tissue injury so know both probably) ○ Example: Breast indentation from blunt force trauma, pancreatitis Gangrenous Necrosis- not a specific cell pattern death but it is the term used. Normally in reference to a limb (often lower) that has lost its blood supply and is necrosed. When bacteria gets involved, it recruits leukocytes to the area and causes there to be more liquefactive necrosis due to the digestive enzymes of the bacteria and the leukocyte response, which gives the term wet gangrene. ○ Example: Wet gangrene Caseous Necrosis- most often seen in foci of TB infection. Caseous means “cheeselike” and appears as a friable white area of necrosis. Often presents with granulomas. ○ Example: Tuberculosis Fibrinoid Necrosis- a special form of vascular damage usually seen in immune reactions involving blood vessels. Complexes of antibodies and antigens are deposited in the walls of arteries. These plus plasma proteins result in pink appearance on an H&E stain. ○ Example: Malignant HTN 2. Cellular Adaptation Define and identify examples of the types of cellular adaptations. (For example hyperplasia) Hypertrophy- increase in the cell size that results in increased organ size. Cardiomegaly, Ventricular hypertrophy, Cardiomyopathy. Uterine enlargement during pregnancy. Atrophy- reduction in size of an organ due to decrease in cell size, number. Chronic loss of blood supply causing Senile atrophy. Loss of innervation or loss of workload (skeletal muscle loss) Hyperplasia- increase in the number of cells in an organ or tissue. Hormonal Hyperplasia i.e. periods, PCOS, hepatic regeneration Metaplasia- reversible cell change where a cell type is replaced by another cell type. Not due to a change in phenotype. Smokers losing cilia in lung cells. Dysplasia- disordered growth. Cells showing irreversible changes in cell type. HPV causing epithelial cells to change into cancerous cells. 3. Patho associated with cellular damage Differentiate necrosis, apoptosis, and autophagy. What parts of the cell are damaged and what are the physiological responses that occur as a result of cell injury? Necrosis- Pathological process due to severe injury. Breakdown of cellular proteins, leaking of cellular contents due to broken membranes, local inflammation, and enzymatic digestion of the cell. a. Release of specific enzymes (biomarkers) during necrosis is how we identify cell death, i.e. troponin for cardiac, alkaline phosphatase for bile duct, transaminases for hepatocytes. i. Cellular swelling, Nuclear pyknosis, karyorrhexis and karyolysis, Disrupted plasma membrane, Enzymatic digestion, Frequent adjacent inflammation, Usually pathologic and irreversible. Autophagy- Process in which a cell eats its own contents. Can be due to multiple reasons such as aged cells, dysfunctional cells, cells in need of cellular repair (eventually leading to apoptosis if repair cannot be achieved). Also triggered by environmental nutrient depletion and need for energy. Lack of growth hormone production. Autosomes fuse with lysosomes to eat cytoplasmic particles. b. Dysregulation of this process is in many diseases, cancer, IBS, neurodegenerative disorders.  Apoptosis- Cellular suicide. Programmed by the cell due to damaged DNA in order to prevent replication of damaged cells and keep a tight ship on the number of cells within a specific area. This process eliminates damaged cells without causing a host reaction, therefore no collateral damage is done. c. Intrinsic Pathway (Mitochondrial)- most common method for apoptosis. Mitochondrial walls increase permeability and release pro-apoptotic molecules into the cytoplasm that is triggered by loss of survival cell signal, DNA damage, and accumulation of misfolded proteins (ER stress). Release of caspace (enzymes that are involved in cell death) d. Extrinsic Pathway (death receptor-initiated)- initiated by engagement of plasma membrane death receptors. Death receptors are tumor necrosis factor (TNF) receptors that stop lymphocytes from coming to the rescue and are a mechanism of cell killing by cytotoxic T cell release. e. Execution Pathway- The intrinsic and extrinsic pathways combine to activate a caspase cascade which allows for the final apoptosis process. i. Cellular shrinkage, Nuclear fragmentation, Intact membrane with disoriented structures (mainly lipids), Intact cellular contents, No inflammation, Often physiologic unless in the case of DNA damage, then it is pathological. 4. Tumor Staging Grading of a cancer is based on: the degree of differentiation of the tumor cells the number of mitoses or architectural features. staging of solid cancers is based on : the size of the primary lesion, whether it has spread to regional lymph nodes the presence or absence of blood-borne metastases. Inflammation and Infectious Disease 1. HIV *** I did not add all of HIV because we had a lot and I did not have much highlighted but feel free to expand on it*** HIV - How HIV infects the cells, roughly define the times patient’s spend in each state (acute, seroconversion, latency, transition to AIDS), how the disease progresses and affects immune system (starts at slide 59) How HIV infects the cells - look at photo → ○ HIV are attracted to CD4+ receptors ○ gp120 BINDS to CD4+ receptors This point T-cells (CD4+) are triggered - APOPTOSIS ○ Chemokine receptor (CCR-5) (co-receptor) MUST be present for the virus to enter the host cell ○ gp41 PENETRATES/IMPLANTS in cell Roughly define the times patient’s spend in each state ○ Acute HIV virion (when virus has become actual HIV in the body LOL) enters the body and replicates fast! Seen in blood and CSF but cannot be detected by a lab test. Usually ASYMPTOMATIC.  Acute (early) infection = when CD4+ cells are infected in mucosal lymphoid tissues and death of many infected cells HIV IS REPLICATED IN LYMPH NODES ○ Seroconversion ANTIBODIES PRESENT in blood. Seen between 3 weeks - 6 months after exposure S/S of ACUTE RETROVIRAL SYNDROME (“ARSe”) - basically primary HIV infection develops at this stage Flu- or MONO-like symptoms Rash CD4+ T cells count is high (>400 cells/µL) ↓ WBCs (e.g. lymphocytes), BUT ↑ in CD8+ T cells ↓ Platelets ↑ ESR HIV seen in genital fluids are high, DUH. INFECTIOUS! Latency 😲 ○ This period ranges from 3-12 years! Gradual lymph tissue destruction Virus production plateaued at a set level CD4+ T cells count is high still (>400 cells/µL) Virus is ACTIVE - producing 2 millions NEW virions daily Person feels well but can have chronic lymphadenopathy or mild symptoms AFTER LATENCY PERIOD Period up to 18 months DROP in CD4+ T-cell count, less than 400 cells/µL Innate immune activity is less effective as viral load increases 2. Acute Viral Infections Viral infections, such as infectious mononucleosis, mumps, and German measles, cause an absolute increase in the number of lymphocytes (lymphocytosis). The nature of the leukocyte infiltrate varies with the age of the inflammatory response and the type of stimulus. In most forms of acute inflammation, neutrophils predominate in the inflammatory infiltrate during the first 6 to 24 hours and are replaced by monocytes in 24 to 48 hours Once leukocytes (particularly neutrophils and monocytes) are recruited to a site of infection or cell death, they must be activated to perform their functions. Recognition of microbes or dead cells induces several responses in leukocytes that are collectively called leukocyte activation ○ In bacterial infections: Neutrophils rise first, followed by lymphocytes ○ In Viral infections: Lymphocytes rise initially ○ In helminthic infections or allergic reactions: eosinophils may be the predominate WBC Leukocytes are important causes of injury to normal cells and tissues under several circumstances. ○ Adjacent tissues suffer collateral damage. ○ In some infections that are difficult to eradicate, such as TB, the prolonged host response contributes more to the pathology than does the microbe itself. ○ Occurs when the inflammatory response is inappropriately directed against host tissues, as in certain autoimmune diseases. ○ Or the host reacts excessively against usually harmless environmental substances, as in allergic diseases, including asthma. Leukocyte Infiltration The nature of the leukocyte infiltrate varies with the age of the inflammatory response and the type of stimulus. ○ In most forms of acute inflammation, neutrophils predominate in the inflammatory infiltrate during the first 6 to 24 hours and are replaced by monocytes in 24 to 48 hours Once leukocytes (particularly neutrophils and monocytes) are recruited to a site of infection or cell death, they must be activated to perform their functions.  Recognition of microbes or dead cells induces several responses in leukocytes that are collectively called leukocyte activation In bacterial infections: Neutrophils rise first, followed by lymphocytes In Viral infections: Lymphocytes rise initially In helminthic infections or allergic reactions: eosinophils may be the predominate WBC - After entering tissues, neutrophils are short-lived; most neutrophils in extravascular tissues undergo apoptosis within a few days. Monocytes not only survive longer but may also proliferate in the tissues, and thus they become the dominant population in prolonged inflammatory reactions. Mechanisms of Viral Injury Determined by the presence of viral receptors on host cells Direct cytopathic effects- kill cells by preventing synthesis of critical host macromolecules or producing degradative enzymes and toxic proteins. Viruses can induce cell death by activating so-called death receptors on the plasma membrane and by triggering apoptosis Transformation of infected cells. Oncogenic viruses can stimulate cell growth and survival by a variety of mechanisms, including expression of virus-encoded oncogenes, expression of viral proteins that inactivate tumor suppressors, and insertional mutagenesis - cytotoxic T lymphocytes (CTLs) - Viruses can directly damage host cells by entering them and replicating at the cell's expense. The predilection for viruses to infect certain cells and not others is called tropism. A major determinant of tissue tropism is the presence of viral receptors on host cells. Viruses bind to proteins found on the surface of host cells that normally function as receptors for host factors. 3. Histamine Reaction Changes in vascular flow and caliber begin early after injury ○ Vasodilation is induced by several mediators, notably histamine, on vascular smooth muscle. Increased Vascular Permeability (Vascular Leakage) ○ Elicited by histamine, bradykinin, leukotrienes, and other chemical mediator ○ Called the immediate transient response because it occurs rapidly after exposure to the mediator and is usually short-lived (15 to 30 minutes). ○ Endothelial injury resulting in endothelial cell necrosis and detachment Cell-derived mediators are normally sequestered in intracellular granules and can be rapidly secreted by granule exocytosis (e.g., histamine in mast cell granules) or are synthesized de novo (e.g., prostaglandins and leukotrienes, cytokines) in response to a stimulus. ​Histamines: The richest source of histamine are mast cells that are normally present in the connective tissue adjacent to blood vessels. ○ Histamine causes dilation of arterioles and increases the permeability of venules. ○ Histamine is stored in mast cell granules and is released by mast cell degranulation in response to a variety of stimuli physical injury (such as trauma), cold, and heat, all by unknown mechanisms binding of antigen to IgE antibodies displayed on the surfaces of mast cells, which underlies immediate hypersensitivity (allergic) reactions products of complement called anaphylatoxins Inflammation: stimulate histamine release from mast cells and thereby increase vascular permeability and cause vasodilation. ○ Patients with chronic atopic diseases such as asthma and atopic dermatitis are sometimes classified into Th2-high and Th2-low based on biomarkers that reflect the intensity of the pathologic T-cell response in individual patients. This separation may serve as a guide to therapy, as antagonists of Th2 cytokines (IL-4, IL-5) are predictably most effective in the Th2-high group. ○ Vasoactive amines. The most important mast cell–derived amine is histamine (Chapter 3). Histamine causes intense smooth muscle contraction, increases vascular permeability, and stimulates mucus secretion by nasal, bronchial, and gastric glands. ○ Leukotrienes. Leukotrienes C4 and D4 are the most potent vasoactive and spasmogenic agents known. On a molar basis, they are several thousand times more active than histamine in increasing vascular permeability and causing bronchial smooth muscle contraction. Leukotriene B4 is highly chemotactic for neutrophils, eosinophils, and monocytes. ○ Prostaglandin D2. This is the most abundant mediator produced in mast cells by the cyclooxygenase pathway. It causes intense bronchospasm and increases mucus secretion. ○ Platelet-activating factor (PAF). is a lipid mediator produced by some mast cell populations that is not derived from arachidonic acid. It causes platelet aggregation, histamine release, bronchospasm, increased vascular permeability, and vasodilation. Its role in immediate hypersensitivity reactions is not well established.  4. Hypersensitivity Reactions Differentiate between the different types of hypersensitivity reactions both physiologically and through clinical examples. (Slides 37-46 Page 204) Type I (Immediate Hypersensitivity): Type II (Antibody mediated hypersensitivity) : IgE IgG & IgM Antibodies by B lymphocytes Antibodies by B lymphocytes Systemic: anaphylaxis (examples: allergies, asthma, bee sting, peanut allergy) React with antigens present on the cell surface, leading to destroying these Vascular shock, widespread edema, and difficulty breathing cells, triggering inflammation, or interfering with normal functions. Local - 2 phases Phagocytosis → Fc receptors 1. Immediate: vasodilation, vascular leak, MM spasm, or glandular Activating complement system secretions Recruits leukocytes 2. Late phase, 2-24 hrs post exposure, can last several days Examples: Autoimmune hemolytic anemia, Grave’s disease, transfusion Infiltration of tissue with eosinophils, neutrophils, reactions, Goodpasture syndrome (autoimmune disease that affects lungs & basophils, monocytes and CD4+ T-cells, plus tissue kidneys), Acute rheumatic fever, pernicious anemia destruction Type III (immune complex hypersensitivity): Type IV (Cell-mediated hypersensitivity): IgG & complement system Mediated by T cells Antigen-antibody complexes produces tissue damage mainly by eliciting Activates T lymphocytes → Release of cytokines, inflammation & macrophage inflammation at the sites of deposition activation → CD4+ T-cell mediated cytotoxicity Examples: SLE, glomerulonephritis, serum sickness, arthrus reaction (hard, Examples: contact dermatitis, multiple sclerosis, RA, DMI, TB, IBD, psoriasis, painful area post booster vaccination) contact sensitivity, PPD, posion ivy, drug reactions Possible etiologies: recent history of infection or persistent low-grade infection by microbial or viral agent, extrinsic environment (molds, plants, or animals), autoimmune process (autoantibodies attack self antigens) 5. Measles Measles (slide 75, p. 350) Measles - Acute viral infection affecting multiple organs and ranges from mild, self-limited infections to severe systemic manifestations. ○ Single-stranded RNA virus of the Paramyxoviridae family ○ Transmitted by the airborne route via aerosolized respiratory secretions. Initially multiplies within the respiratory tract and then spreads to local lymphoid tissues. ○ Antibody-mediated immunity to measles virus protects against re-infection. ○ The blotchy, reddish brown rash of measles virus infection on the face, trunk, and proximal extremities is produced by dilated skin vessels, edema, and a mononuclear perivascular infiltrate. ○ Ulcerated mucosal lesions in the oral cavity near the opening of the Stensen ducts (Koplik spots) 6. Abscess Abscesses are localized collections of pus The most frequent cause of purulent (also called suppurative) inflammation is infection with bacteria that cause liquefactive tissue necrosis, such as staphylococci; these pathogens are referred to as pyogenic (pus-producing) bacteria. A common example of an acute suppurative inflammation is acute appendicitis. Abscesses have a central liquefied region composed of necrotic leukocytes and tissue cells. There is usually a zone of preserved neutrophils around this necrotic focus, and outside this region there may be vascular dilation and parenchymal and fibroblastic proliferation, indicating chronic inflammation and repair. In time the abscess may become walled off and ultimately replaced by connective tissue. Staphylococcal infections (slide 78, p. 359) (adding this for the abscess reason) S. aureus causes a myriad of skin lesions (boils, carbuncles, impetigo, and scalded-skin syndrome) as well as abscesses, sepsis, osteomyelitis, pneumonia, endocarditis, food poisoning, and toxic shock syndrome S. aureus produces a multitude of virulence factors:  ○ Surface proteins involved in adherence and evasion of the host immune response ○ Secreted enzymes that degrade host structures ○ Secreted toxins that damage host cells ○ And proteins that cause antibiotic resistance. S. aureus produces multiple membrane-damaging (hemolytic) toxins. ○ Example: kid has microhemorrhages in the back of their throat S. aureus causes pyogenic inflammation that is distinctive for its local destruction of host tissue. Antibiotic resistance is a growing problem in the treatment of S.aureus infections. Methicillin-resistant S. aureus (MRSA) are resistant to nearly all penicillin and cephalosporin antibiotics. 7. SLE SLE (slide 49-52, p. 221) Systemic Lupus Erythematosus (SLE) - autoimmune disease involving multiple organs, characterized by a vast array of autoantibodies, particularly antinuclear antibodies (ANAs), in which injury is caused mainly by deposition of immune complexes and binding of antibodies to various cells and tissues. Immune Complex - Mediated (Type III) Hypersensitivity May be acute or insidious in its onset, and is typically a chronic, remitting, and relapsing, often febrile, illness. Hallmark of SLE is the production of autoantibodies, several of which (antibodies to double-stranded DNA and the so-called Smith [Sm] antigen) are diagnostic. ANAs: These are directed against nuclear antigens and can be grouped into four categories based on their specificity for: (1) DNA, (2) histones, (3) nonhistone proteins bound to RNA, and (4) nucleolar antigens. Clinical Features of SLE With appropriate therapy, the disease follows a relapsing Butterfly rash over the face and remitting course spanning a period of years or even Fever decades. Pain but no deformity in one or more peripheral joints (feet, The most common causes of death are renal failure and ankles, knees, hips, fingers, wrists, elbows, shoulders) concurrent infections. Pleuritic chest pain Photosensitivity Coronary artery disease is also becoming an important Pericarditis is the most predominant and common cardiovascular cause of death. manifestation Chronic Discoid Lupus Erythematosus - (discoid means shaped like a disk, think disk = plaques) Skin manifestations may mimic SLE, but systemic manifestations are rare. Presence of skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy surrounded by an elevated erythematous border. Subacute Cutaneous Lupus Erythematosus Appears to define a group of patients with features intermediate between SLE and chronic discoid lupus erythematosus. The skin rash tends to be widespread, superficial, and nonscarring (though exceptions occur). Secondly, most patients have mild systemic symptoms consistent with SLE. There is a strong association with antibodies to the SS-A antigen and with the HLA-DR3 genotype. Drug-Induced Lupus Erythematosus An SLE-like syndrome may develop in patients receiving a variety of drugs, including hydralazine, procainamide, isoniazid, and D-penicillamine, to name a few. There are serologic and genetic differences from classic SLE, as well. Antibodies specific for double-stranded DNA are rare, but there is an extremely high frequency of antibodies specific for histones. 8. Malaria Malaria (Slide 82, Page 388)symptom Malaria is a life-threatening disease caused by an intracellular parasite(Plasmodium - falciparum, vivax, ovale, nowlesi, and malariae) that is spread to humans by certain types of mosquitoes. P. falciparum infection - high levels of parasitemia that can lead to severe anemia, cerebral symptoms, renal failure, pulmonary edema, and death. Sporozoites are released in the bloodstream and attach to liver cells binding to hepatocyte receptors for the serum proteins thrombospondin and properdin.  In the liver cells, malarial parasites multiply and release merozoites when each infected hepatocyte ruptures. ○ Rupture occurs 8-12 weeks Symptoms: paroxysmal fever, chills, and rigor Red cell sequestration decreases tissue perfusion → ischemia → death (in children with malaria) Found in sub-Saharan Africa, Oceania, Central and South America, and Southeast Asia. EXAM 2 EENT 1. Cholesteatoma Non-neoplastic, cystic lesions associated with chronic otitis media Cysts are typically 1 to 4 cm in diameter, lined by keratinizing squamous or metaplastic mucus-secreting epithelium, and filled with amorphous, keratinous debris Cholesterol spicules may be present Pathogenesis is not clear​ ○ thought that chronic inflammation and perforation of the eardrum, with ingrowth of the squamous epithelium or metaplasia of the secretory epithelial lining of the middle ear, promote the formation of a squamous cell nest that becomes cystic Lesions, by progressive enlargement, can erode into the ossicles, labyrinth, adjacent bone, or surrounding soft tissue and sometimes produce visible neck masses. Cholesteatoma: Understand what cholesteatomas are, how they develop, and their clinical significance. 2. Pterygium a fleshy overgrowth of the conjunctiva, which is the thin clear membrane on the surface of the eye. A pinkish, triangular growth that starts on the cornea near the nose and extends onto the white of the eye. It can be slightly raised and contain visible blood vessels It can cause irritation, redness, a feeling of something in the eye, or decreased vision. If the growth grows onto the cornea, it can cause blurred or double vision The cause is unclear, but it's more common in people who spend a lot of time outdoors without eye protection. It's also more common in older adults and people who live near the equator Minor cases can be treated with eye drops or ointment to reduce inflammation. More serious cases may require surgery to remove the growth Pinguecula is a yellowish, raised growth on the conjunctiva. It's usually on the side of the eye near your nose, but can happen on the other side too. A pinguecula may contain deposits of protein, fat, or calcium. Pterygium is a growth of fleshy tissue (has blood vessels) that may start as a pinguecula. A pinguecula can become a pterygium, growing onto the cornea and blocking vision. Pterygium is also known as “surfer's eye” or “farmer's eye.” This is because people who spend long hours in the sun or in dusty, dry conditions are at risk for developing this growth.. 3. Macular Degeneration One of the most common causes of irreversible vision loss in patients over 65 years old; results in central vision loss due to damage to the macula Considered a multifactorial disease, with environmental and genetic elements as the main risk factors. ​ Dry AMD is characterized by a slowly progressive loss of visual function, owing to deterioration of the choriocapillaris, atrophic loss of the outer retina, and disruption and eventually death of the photoreceptor layer.​ ○ sometimes progresses to severe blindness. No treatment.​ Wet AMD involves the recruitment of immune cells to the damaged macula and secretion of proinflammatory and proangiogenic cytokines, particularly Vascular endothelial growth factor (VEGF). ​  ○ VEGF stimulates endothelial cell proliferation and migration and leads to angiogenesis and increased vascular permeability. The newly growing blood vessels leak fluid, disrupting and damaging the layer of photoreceptors and impairing vision.​ ○ affects only 10–15% of AMD patients, emerges abruptly, and rapidly progresses to blindness if left untreated AMD results from damage to the macula, which is required for central vision. It occurs in two forms, dry and wet, that are distinguished by the presence of neoangiogenesis in the wet form and its absence in the dry form. advancing age is a risk factor Aging of the eye is accompanied by the buildup of uncleared cellular debris that originates from the retinal pigment epithelium (RPE) and accumulates where the RPE interfaces with Bruch’s membrane and the neurosensory retina. ○ These deposits, known as drusen, typically are the first ophthalmoscopic sign of AMD, appearing before visual function is appreciably affected. Drusen deposition in Bruch’s membrane concomitant with other structural and biochemical changes associated with AMD pathogenesis (including persistent activation of the complement cascade and inflammation) lead to thickening and decreased permeability of the membrane. ○ This obstructs both nutrient transport to the retina and waste exchange to the choroid and is accompanied by thinning of the choroidal vasculature. These steps, combined with neurodegenerative changes within the photoreceptor-RPE complex, result in pigmentary abnormalities of the RPE, including hypo or hyperpigmentation, in early or intermediate stages of disease. This combination of factors results in impaired RPE and photoreceptor function 4. Allergic Rhinitis (Hay Fever) initiated by hypersensitivity to one of a large group of allergens, most commonly plant pollens, fungi, animal allergens, and dust mites​ affects 20% of the US population​ IgE-mediated immune reaction with an early- and late-phase response​ characterized by mucosal edema, erythema, and mucus secretion accompanied by eosinophil-rich leukocytic infiltrates 5. Blepharitis Anterior blepharitis, affecting the outside front of the eyelid where eyelashes are attached.​ ○ Lid, skin, eyelashes, and associated glands affected​ ○ May be ulcerative (staphylococci or seborrheic in association with seborrhea of the scalp, brows, and ears)​ Posterior blepharitis, linked to dysfunction of Meibomian glands within the eyelids that secrete oils to help lubricate the eye.​ Trichiasis –epithelial keratitis of the lower third of the cornea, corneal infiltrates and inferior corneal vascularization and thinning caused by Abnormal lid or lash positions 6. Otosclerosis abnormal bone deposition in the middle ear about the rim of the oval window into which the footplate of the stapes fits​ ○ Begins with bone resorption, followed by fibrosis and vascularization ​of the temporal bone in the immediate vicinity of the oval window. ​ ○ Over time the fibrosis is replaced by dense new bone anchoring the footplate of the stapes. ​ ○ process is slowly progressive over the span of decades and can eventually lead to marked hearing loss.​ Both ears are usually affected; the severity of the hearing loss reflects the degree of immobilization.​ Minimal degrees of otosclerosis is common in young to middle-aged adults, but fortunately more severe symptomatic disease is relatively rare​ ○ familial in most instances, with an autosomal dominant transmission and variable penetrance​ 7. Cataracts Clouding of the lens of the eye. Proteins in the lens break down and cause things to look blurry, hazy, or less colorful.​ Most cataracts develop slowly over time. Can be surgically removed procedure that restores vision in nearly everyone.​ may be congenital or acquired​ Age-related cataract typically results from opacification of the lens nucleus (nuclear sclerosis)​ Accumulation of urochrome pigment may render the lens nucleus brown, thus distorting the individual’s perception of the blue color Clinical Manifestations: ​ ○ Having blurry vision​ ○ Seeing double or a ghosted image out of the eye with cataract ​  ○ Being extra sensitive to light (especially with oncoming headlights at night); Halos​ ○ Having trouble seeing well at night, or needing more light when you read​ ○ Seeing bright colors as faded or yellow instead​ ​ Age-related cataracts. Most cataracts are related to aging.​ Congenital cataracts. Some babies are born with cataracts. Some children develop them in childhood, often in both eyes. Some congenital cataracts do not affect eyesight, but others do and need to be removed.​ Secondary cataracts. Secondary cataracts usually happen because of another disease in the body (such as diabetes). Secondary cataracts have also been linked to steroid use.​ Traumatic cataracts. An injury to one or both eyes may cause you to develop a traumatic cataract. This can happen either right after the accident or several years later. Genetics and Childhood disorders and Principles of Neoplasia 1. Turner Syndrome (Monosomy X) Monosomy X: 45X​ Occurs when the 2nd copy of the X chromosome is altered or missing, causing abnormal development.​ characterized by hypogonadism in phenotypic females. ​ Genitalia remains infantile, breast development is inadequate, and little pubic hair. ​ Approximately 57% are missing an entire X chromosome, resulting in a 45,X karyotype​ Mosaic patients have a 45,X cell population along with one or more karyotypically normal or abnormal cell types.​ At puberty there is a failure to develop normal secondary sex characteristics. ​ The mental status varies by degree of genetic dysfunction. Neck webbing-most severely affected patients generally present during infancy with edema of the dorsum of the hand and foot due to lymph stasis and sometimes swelling of the nape of the neck. Turner syndrome is the single most important cause of primary amenorrhea, accounting for approximately one-third of the cases. For reasons that are not clear, approximately 50% of patients develop autoantibodies that react with the thyroid gland, and up to half of these develop clinically manifest hypothyroidism. Equally mysterious is the presence of glucose intolerance, obesity, nonalcoholic fatty liver disease, and insulin resistance in a subset of patients. Some have full-fledged metabolic syndrome. The occurrence of insulin resistance is significant because therapy with growth hormone, commonly used in these patients, worsens insulin resistance. 2. Neonatal Respiratory Distress (hyaline membrane disease​) Etiology: Deposition of a layer of hyaline proteinaceous material in the peripheral airspaces of infants who succumb to this condition​​ Pathogenesis: fundamental defect in RDS is pulmonary immaturity and deficiency of surfactant​ Surfactant production by type II alveolar cells is accelerated after the 35th week of gestation in the fetus.​ a deficiency of surfactant, the lungs collapse with each successive breath, so infants must work as hard with each successive breath ​ Progressive atelectasis and reduced lung compliance then lead to a chain of events, resulting in protein-rich, fibrin-rich exudation into the alveolar spaces with the formation of hyaline membranes. The fibrin-hyaline membranes are barriers to gas exchange, leading to carbon dioxide retention and hypoxemia.​ often within 30 minutes, breathing becomes more difficult, and within a few hours cyanosis becomes evident in the untreated infant. ○ Fine rales can then be heard over both lung fields. ○ A chest x-ray usually reveals uniform minute reticulogranular densities, producing a ground-glass picture. ○ cyanosis increases If therapy staves off death for the first 3 or 4 days, the infant has an excellent chance of recovery. Complications of RDS ○ Retinopathy of Prematurity: Vision impairment caused by abnormal retinal development. ○ Bronchopulmonary Dysplasia: Chronic lung disease due to prolonged mechanical ventilation. ○ Patent Ductus Arteriosus, Intraventricular Hemorrhage, Necrotizing Enterocolitis. 3. PKU (Phenylketonuria) Patho: inborn error of metabolism, which affects 1 in 10,000 live-born Caucasian infants​  autosomal recessive disorder caused by a severe deficiency of the enzyme phenylalanine hydroxylase (PAH) leading to hyperphenylalaninemia​ Usually by 6 months of life, severe intellectual disability becomes evident​ The biochemical abnormality in PKU is an inability to convert phenylalanine into tyrosine.​ Risk: Mutations in both PAH alleles are required to develop the disease S/S: About one-third of these children are never able to walk​, two-thirds cannot talk​, Seizures, other neurologic abnormalities​, decreased pigmentation of hair and skin​, a characteristic musty odor​, eczema Hyperphenylalaninemia and the resultant intellectual disability can be avoided by restricting phenylalanine intake early in life. Hence, all states in the United States have adopted screening procedures to detect PKU in the immediate postnatal period. Many female PKU patients, if treated with dietary restriction early in life, reach childbearing age and are clinically asymptomatic. Most of them have marked hyperphenylalaninemia, because dietary treatment is discontinued after they reach adulthood. Between 75% and 90% of children born to such women have intellectual disability and are microcephalic, and 15% have congenital heart disease, even though the infants themselves are heterozygotes. This syndrome, termed maternal PKU, results from the teratogenic effects of phenylalanine or its metabolites that cross the placenta and affect specific fetal organs during development. The presence and severity of the fetal anomalies directly correlate with the maternal phenylalanine level, so it is imperative that maternal dietary restriction of phenylalanine be initiated before conception and continued throughout pregnancy. 4. Familial Hypercholesterolemia Familial Hypercholesterolemia Patho: characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) that leads to atherosclerotic plaque deposition in the coronary arteries and proximal aorta at an early age and increases the risk of premature cardiovascular events such as angina and myocardial infarction​ ○ Mutation of the gene encoding the receptor for LDL results in inadequate removal of plasma LDL by the liver.​ Caused by mutations in LDLR (85%), APOB (5-10%), or PCSK9 (1-2%).​ Heterozygotes (1 in 200 individuals) have 2-3x elevated cholesterol levels​ Homozygotes, having a double dose of the mutant gene, are much more severely affected and may have 5-6x elevations in plasma cholesterol levels. ​ ○ Myocardial infarction may occur before age 20 years. Mutations in LDLR gene. Heterozygotes with FH due to mutation in the LDLR gene possess only 50% of the normal number of high-affinity LDL receptors because they have only one normal gene. As a result of this defect in transport, the catabolism of LDL by the receptor-dependent pathways is impaired, and the plasma level of LDL increases two- to three-fold. Homozygotes have virtually no normal LDL receptors in their cells and have much higher levels of circulating LDL. In addition to defective LDL clearance, both the homozygotes and the heterozygotes have increased synthesis of LDL. The increased synthesis that contributes to hypercholesterolemia also results from a lack of LDL receptors (see Fig. 5.6). As mentioned above, IDL, the immediate precursor of plasma LDL, also uses hepatic LDL receptors (apoB/E receptors) for its transport into the liver. Mutations in gene encoding ApoB. Since ApoB on the surface of LDL particles is the ligand for LDL receptors, mutant ApoB reduces the binding of LDL molecules with LDL receptors. This compromise in the binding of LDL particles to its receptors increases serum LDL cholesterol. Activating mutation in the PCSK9 gene. This mutation greatly reduces the number of LDL receptors on the cell surface because of their increased degradation during the recycling process. 5. Klinefelter Occurs when males have an extra copy of the X chromosome (47,XXY) due to meiotic nondisjunction, causing reduced testosterone production and abnormal sexual development.​ The clinical features of Klinefelter syndrome can be attributed to two major factors:​ ○ (1) aneuploidy and the impact of increased gene dosage by the supernumerary X ​ ○ (2) the presence of hypogonadism.​ Rarely diagnosed before puberty, particularly because manifestations of hypogonadism do not develop before early puberty.​ an important genetic cause of reduced spermatogenesis and male infertility.  one of the most frequent forms of genetic diseases involving the sex chromosomes as well as one of the most common causes of hypogonadism in males. The incidence of this condition is reported to be approximately 1 in 660 live male births Most patients have a distinctive body habitus with an increase in length between the soles and the pubic bone, which creates the appearance of an elongated body. ○ Also characteristic are eunuchoid body habitus with abnormally long legs; small atrophic testes often associated with a small penis; and lack of such secondary male characteristics as deep voice, beard, and male distribution of pubic hair. ○ Gynecomastia may be present. The cognitive abilities range from average to below average with modest deficit in verbal skills particularly those that are used in reading and language comprehension. ○ Patients with Klinefelter syndrome develop several comorbid conditions. There is increased incidence of type 2 diabetes and the metabolic syndrome that gives rise to insulin resistance. ○ Patients are at a higher risk for congenital heart disease, particularly mitral valve prolapse, which is seen in about 50% of adults. In addition there is a higher prevalence of atrial and ventricular septal defects. There is also an increased incidence of osteoporosis and fractures due to sex hormonal imbalance. Patients with Klinefelter syndrome have a 20- to 30-fold higher risk of developing extragonadal germ cell tumors, mostly mediastinal teratomas. In addition, breast cancer and autoimmune diseases such as systemic lupus erythematosus occur more frequently. Advanced maternal age (>40 years) is a risk factor. EXAM 3 Diseases of the skin 1. Molluscum Molluscum Patho: Poxyvirus infection that is spread via close contact Exam: Multiple lesions may occur on the skin and mucous membranes, with specifically the trunk and anogenital (adults d/t sexual transmission) areas. Lesions are firm, often pruritic, pink to skin-colored umbilicated papules (main differentiating appearance). A curd-like material can be expressed from the central umbilication. Etiology: poxyvirus exposure Complications: None noted in book or slide Age: All ages children more likely due to close contact and day cares/ schools 2. Tinea Tinea infections Patho: Superficial fungal infection caused by Trichophyton Rubum. Dermatophytes invade, infect, and persist in the stratum corneum. Rarely penetrate below the surface of the epidermis. Different tinea names note the location in which the infection exists. “Tinea” Capitis (scalp), faciei (face), corporis (trunk), manus (hand), cruris (groin), onychomycosis (nail beds. No “tinea” precursor), barbae (beard) Exam: Manifest as erythematous macules or plaques with peripheral scaling and central clearing. Etiology: These organism grow in the soil and are on animals and are endemic in certain areas more than others. Complications: - Corporis- common superficial fungal infection of skin that affects persons of all ages, but particularly children. Predisposing factors include excessive heat and humidity , exposure to infected animals, and chronic dermatophytosis of the feet or nails. Most common type of tinea corporis is an expanding, round, slightly erythematous plaque with an elevated scaling border. - Cruris- Occurs most frequently in the inguinal areas of obese men during warm weather. Heat, friction, and maceration all predispose to its development. Infection usually first appears on the upper inner thighs as moist, red patches with raised scaly borders. - Capitis- usually occurs in children and is only rarely seen in infants and adults. dermatophytosis of the scalp characterized by asymptomatic, patchy skin lesions associated with mild erythema, crust formation, scaling, and frequent hair loss. - Pedis- Affects 30-40% of the population. diffuse erythema and scaling, often initially localized to the web spaces. Most of the inflammatory reaction is a result of bacterial superinfection and is not directly related to the primary dermatophytosis. Spread to (or primary infection of the nails) is referred to as onychomycosis. This produces discoloration, thickening, and deformity of the nail plate. - Versicolor- usually occurs on the upper trunk and is highly distinctive in appearance. Caused by Malassezia furfur (a yeast, not a dermatophyte)!!! The lesions consist of groups of macules of varied size and color with a fine peripheral scale. Age: depends on which manifestation. 3. Acne Acne vulgaris Patho: Multifactoral (1) keratin plug that blocks outflow of sebum to the skin surface (2) hypertrophy of sebaceous glands during puberty under the influence of androgens (3) lipase-synthesizing bacteria (Propionibacterium acnes. [P. acnes]) colonizing the upper and mid-portion of the hair follicle, converting lipids within sebum to proinflammatory fatty acids (4) secondary inflammation of the involved follicle Exam: Open comdomes (central black keratin plug due to oxidation of keratin melanocyte not dirt) and closed comdomes (No visible plug, since the plug is trapped beneath the surface these are sources of follicular rupture and inflammation) Etiology: Could be drug induced (corticosteroids, adrenocorticotopic hormone, testosterone, gonadotropin, contraceptives, trimethadone, ioddides and bromides), occupational exousre (cutting oils, coal tar) heavy clothing, make up, tropical climates and hormonal changes. Complications: Males have a preponderance for more severe version. Scarring anf physical appearance Age: any but mainly pubescent and preganancy (high hormone changes) 4. Vitiligo Vitiligo. Patho: pigment disappears from patches of skin, leading to depigmented areas. Sudden onset of the condition Pathogenic theories: Autoimmune involvement, viral cases, decreased melanocyte survival, genetic defects affecting melanocyte structure, neurochemical destruction of melanocytes. Exam: looking for depigmented patches of skin, which may be localized or generalized Using a Wood’s lamp - clearer view of depigmentation. Etiology: Exact cause is unknown. Complications: Psychosocial effects due to change in appearance, increased risk of sunburn, potential association with other autoimmune diseases. Age: Occur at any age, often starts between ages 10-30. Affects both children and adults. 5. Atopic Dermatitis Eczematous Dermatitis (atopic) vs contact dermatitis Patho Exam Etiology Complications Age Results from external Red papulovesicular Exposure to As long as the allergen Contact application of an antigen crusted lesions in a allergens remains on the skin it Dermatitis (e.g., poison ivy) or a reaction sometimes linear can be spread to non to an internal circulating fashion that is persistent 5 types exposed areas (rolling antigen (which may be can develop acanthosis 1. Atopic around in bed without derived from ingested food and hyperkeratosis and 2.Allergic showering) or a drug). T-cell mediated appear as raised scaling contact Hypersensitivity (IV) plaques 3. Drug related Rhus Dermatitis is most 4. common Photoeczematou s 5. Primary irritant Eczematous Genetic defects in the Lesions pruritic, oozing, Genetic atopy Aesthetic Most Dermatitis epidermal barrier protein crusting, coalescent consideration common in (atopic) filaggrin have been cited as a papule; thickening of the children but major cause. The stratum skin or lichenification improves corneum layers with this occurs with age mutation (loss-of-function of filaggrin) have lower levels of natural moisturizing factor and are also deficient in extracellular lipids including ceramides. 6. Impetigo Impetigo Patho: Common superficial skin bacterial infection (S. Aureus) that is highly contagious and frequently seen in healthy children. The bacteria in the epidermis evoke an innate immune response that causes epidermal injury with serous exudate and formation of scale crusts (scabs). Exam: Starts as an erythematous macule that rapidly progresses to multiple small pustules that eventually rupture. Two differing types that are seen. Formation of vesicles, pustules and yellow honey-colored crusts - Impetigo contagiosa: smaller pustules - Impetigo bullosa: larger pustules Etiology: S. aureus exposure and exposure to those infected and with open sores Complications: Can also present in adults that are immunocompromised. If the crusts are not removed more erythema forms around the periphery of the crusts. Age: Often affects young children 7. Psoriasis Psoriasis Patho: Psoriasis is a chronic, inflammatory, autoimmune disorder influenced by both genetic and environmental factors. Involves HLA gene variants, which sensitized CD4+ T-cells. These cells infiltrate the skin, triggering the overexpression of cytokines, including TNF-ɑ and various interleukins. The cytokine release stimulates keratinocyte proliferation, leading to the characteris thickened, scaly skin lesions. This causes a cycle of exaggeration and remission. Exam: Common areas are the elbows, kees, scalp, lumbosacral region, intergluteal cleft, and glans penis Typical lesion: well-demarcated, pink to salmon-colored plaques covered by loosely silver-while scales. Auspitz sign: Removal of the scale from the plaque reveals small bleeding points due to proximity of vessels to the overlying skin. Nails - yellow-brown discoloration (resembling an oil slick), pitting, dimpling, thickening, and separation of the nail plate from the nail bed (onycholysis) Etiology: Combination of genetic predisposition and immune system dysfunction. Triggered by environmental factors such as stress, infections, trauma, and certain medications. Complications: psoriatic arthritis (causes joint pain and inflammation), erythroderma (erythema and scaling), nail changes, increased risk of CV disease, metabolic syndrome, and depression Age: Early onset (ages 15-35) and late onset (ages 50-60) Diseases of the Hematologic System 1. Von Willebrand Von Willebrand - *** I have a note that says platelet adhesion *** Most common inherited bleeding disorder of humans, affecting about 1% of adults in the United States Patho - a common, inherited, genetically and clinically heterogeneous hemorrhagic disorder caused by a deficiency or dysfunction of the protein termed von Willebrand factor (vWF). In vWD, defective vWF interaction between platelets and the vessel wall impairs primary hemostasis. Because a deficiency of vWF decreases the stability of factor VIII, type 1 and type 3 von Willebrand disease are associated with a prolonged PTT. Type 1 and type 3 von Willebrand disease are associated with quantitative defects in vWF. Type 2 von Willebrand disease is characterized by qualitative defects in vWF Exam - The most common presenting symptoms are spontaneous bleeding from mucous membranes (e.g., epistaxis), excessive bleeding from wounds, or menorrhagia. It is usually transmitted as an autosomal dominant disorder, but rare autosomal recessive variants also exist Etiology - usually caused by an inherited gene abnormality Complications - bleeding, anemia, swelling and pain, menstrual problems, joint pain, nose bleed Age - any age but median is 33-42, 76% of men with VWD are diagnosed by age 10, but 50% of women are not diagnosed until after age 12 2. Pernicious Anemia Pernicious anemia Patho: Pernicious anemia is a specific form of megaloblastic anemia caused by autoimmune gastritis, which impairs the production of intrinsic factor (IF). IF is essential for absorption of vitamin B12 from the gut. About 75% of patients have type 1 antibodies that block vitamin B12 from binding IF. Type II antibodies prevent the binding to vitamin B12. Autoreactive T-cell response triggers gastric mucosal injury and the formation of autoantibodies. This leads to the destruction of IF-secreting cells, causing vitamin B12 deficiency.  Demylination of the dorsal and lateral spinal tracts can lead to CNS lesions, spastic, paraparesis, sensory ataxia, and severe paresthesia of the lower limbs. Exam: Moderate to severe megaloblastic anemia, leukopenia with hypersegmented granulocytes, and low serum vitamin B12. Elevated homocysteine and methylmalonic acid levels. Serum antibodies Shiny,glazed,”beefy” red tongue (atrophic glossitis) and CNS lesion. Diagnosis confirmed by an outpouring of reticulocytes and a rise of hematocrit levels after parenteral vitamin B12 administration. Etiology: Autoimmune response leading to gastric atrophy and destruction of intrinsic factor-secretion parietal cells. Strict vegetarians - plants no cobalamin (vitamin B12) Complications: Demyelination, gastric atrophy, and metaplastic changes. Age: Disease of older adults, median age at diagnosis at 60 years; rare under 30 years of age. 3. Thrombocytopenia Thrombocytopenia a condition that occurs when the platelet count in your blood is too low Patho - a low number of platelets in the blood, which increases the risk of bleeding. Thrombocytopenia occurs when the bone marrow makes too few platelets or when too many platelets are destroyed or accumulate within an enlarged spleen. Bleeding in the skin and bruising occur. Though many types of hereditary thrombocytopenia exist, MYH9-related disease is the most common. A count less than 150,000 platelets/µL is generally considered to constitute thrombocytopenia Exam - Easy or excessive bruising (purpura) Superficial bleeding into the skin that appears as a rash of pinpoint-sized reddish-purple spots (petechiae), usually on the lower legs. Prolonged bleeding from cuts Etiology - Common causes include infections, medications, an autoimmune disease, inherited or acquired bleeding disorders, an enlarged spleen for any reason, liver disease, or an inherited immune deficiency or disorder. Thrombocytopenia is often caused by medical conditions or certain medications Complications - Thrombocythemia and thrombocytosis may cause blood clots which can block blood flow to your organs. This can lead to the following serious complications: Venous thromboembolism. Stroke and transient ischemic attacks. Gastrointestinal bleeding, heavy menstruation or brain hemorrhages (bleeding within the brain) Age - any age from 3 months to over 100 years of age. About 40% of all patients diagnosed with ITP are children younger than 10 years of age 4. Sickle Cell Sickle cell - ***I have a note that says no fava beans*** an inherited blood disorder, a change in the gene that tells the body to make hemoglobin. In sickle cell disease, abnormal hemoglobin causes red blood cells to become sickle (or crescent) shaped and rigid Patho - an inherited genetic condition that involves defects in the shape and function of hemoglobin in the blood. Sickle cell disease is caused by a missense mutation in the β-globin gene that leads to the replacement of a charged glutamate residue with a hydrophobic valine residue. Howell-Jolly bodies (small nuclear remnants) also are present in red cells due to asplenia. The bone marrow is hyperplastic as a result of a compensatory erythroid hyperplasia Exam - Fatigue, shortness of breath, dizziness, and irregular heartbeat Etiology - is inherited when a child receives two genes—one from each parent—that code for abnormal hemoglobin Complications - Acute chest syndrome, anemia, death of bone tissue, blood clots, fever, infection, kidney problems, leg ulcers, liver problems, organ damage, pain, pulmonary HTN, sleep apnea, stroke Age - 5 or 6 months old 5. G6PD G6PD - when the body is missing or doesn't have enough of an enzyme called G6PD (glucose-6-phosphate dehydrogenase) Patho - G6PD deficiency renders RBCs susceptible to oxidative stress, which shortens RBC survival. Abnormalities in glutathione metabolism (glycolytic pathway) resulting from deficient or impaired enzyme function reducing the ability of red cells to protect themselves against oxidative injuries and leads to hemolysis Exam - pallor, jaundice, fatigue, splenomegaly, and dark urine Etiology - from one or both of the parents. Recessive X-linked trait, placing males at much higher risk for symptomatic disease Complications - enlarged spleen, fatigue, jaundice, dark urine, SHOB, paleness, tachycardia, fever, yellow skin/eyes, hemolytic anemia Age - 17–94 years, in both men and women 6. Anemia of Chronic Disease Complications of CKD and ESRD  HTN & CVD: HYPERVOLEMIA, ESCALATED ATHEROSCLEROTIC PROCESS, HEIGHTENED RAAS AND SNS ACTIVITY Uremic Syndrome: Retention of metabolic wastes, impaired healing, pruritus, dermatitis, uremic frost. Metabolic Acidosis: Retention of acidic waste products; hyperkalemia, kidneys lose ability to secrete H+ ions and bicarb. Electrolyte imbalances: Retained K+, phosphorus and magnesium Bone and mineral disorders: Elevated phosphorus and PTH causes altered bone/mineral metabolism, kidneys unable to reabsorb calcium. Malnutrition: Decreased intake from uremic syndrome depression, dietary limitations, changes in taste, protein-energy wasting. Anemia: Lack of erythropoietin, uremia shortens RBC’s life, combination of CKD, anemia and heart failure (cardiorenal anemia syndrome) Pain: Multiple reasons-disease process, tx, comorbidities. Depression: Comorbid conditions, disease process, disruption of social interactions and relationships 7. Antiphospholipid syndrome Antiphospholipid syndrome (APS) Patho: APS is an autoimmune disorder characterized by the presence of antiphospholipid (aPL) autoantibodies. Can be primary or secondary to other autoimmune diseases (e.g., SLE) Pathogenesis is complex and not fully understood, but aPL antibodies target anionic phospholipids or phospholipid-associated proteins (e.g., cardiolipin, β2-glycoprotein I). ○ β2-glycoprotein I binds to phospholipids on endothelial cells, monocytes, platelets, and thromboplasts, and is believed to play a major role in APS by activating these cells. APS leads to a prothrombotic state due to complement activation, inhibition of fibrinolysis, and endothelial dysfunction. Exam: Recurrent venous or arterial thrombosis (e.g., DVT, PE); Obstetric complications (recurrent miscarriages, fetal death, or premature birth); Cardiac valve vegetations and thrombocytopenia; Pulmonary HTN, CVA, bowel infarction , or renovascular HTN. Etiology Primary APS: Occurs in patients without a known autoimmune disorder (accounts for ~50% of APS cases). Secondary APS: Associated with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE). The production of aPL antibodies (including anti-β2-glycoprotein I antibodies) is central to the pathogenesis. Complications: see exam Age: Adults of reproductive age; primary seen in younger adults; secondary seen in those with pre-existing autoimmune condition, like SLE. EXAM 4 Diseases of the CV and Hemodynamic Disorders 1. RAAS System Renin-Angiotensin-Aldosterone System (RAAS) Renin: Secreted by kidneys in response to low blood pressure, low sodium, or elevated catecholamines. ○ Converts angiotensinogen to angiotensin I, which is converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II: ○ Increases BP by inducing vascular contraction, stimulating aldosterone secretion, and enhancing tubular sodium resorption. Aldosterone: ○ Increases sodium and water resorption in the distal convoluted tubules, elevating blood volume and BP. ○ Vascular Relaxing Substances: Kidneys also produce substances (e.g., prostaglandins, nitric oxide) to counterbalance vasopressor effects. 2. Atherosclerosis Atherosclerosis/CAD *** I have a note that says LDL oxidation *** Primary Patho: (watch some videos, this is a lot) ○ Formation of atherosclerotic plaque is initiated by injury to coronary artery endothelium. Causing permeability and leukocytes recruitment. LDL accumulation occurs with oxidation by endothelial cells and macrophages. Oxidized lipids are damaging to endothelial and smooth muscle cells, and  stimulate recruitment of macrophages into the vessel. Macrophages engulf the lipids.Causing foam cells. Foam cells rupture and release their contents and those are engulfed by more causing increased plaque growth. Excess lipid and debris accumulate forming the lipid core within the vessel wall. Vulnerable plaque are likely due to large lipid core, thin cap and high shear stress increasing rupture likelihood. ○ Lesions called atheromas (atheromatous or atherosclerotic plaques)that protrude into vessel lumens. ○ Atheromatous plaque typically consists of a raised lesion with a soft core of lipid (SEE PIC). They mechanically obstruct blood flow but can also rupture and lead to vascular thrombosis. Due to creating distance between the lumin and media, can cause weakening of the vascular wall and aneurysm formation. ○ Endothelial injury and dysfunction- causes increased vascular permeability, leukocyte adhesion, and thrombosis. EC (endothelial cell) injury is the cornerstone of the “response-to-injury” hypothesis. ○ Early lesions begin at sites of intact endothelium that exhibit features of endothelial dysfunction which are increased permeability, enhanced leukocyte adhesion, and altered gene expression. ○ Causes of EC dysfunction include toxins from cigarette smoke, homocysteine, and the local production of inflammatory cytokines. Three most important causes of endothelial dysfunction are hemodynamic disturbances, hypercholesterolemia, and inflammation. Risk Factors: ○ Family history is the most important independent risk factor. ○ (Nonmodifiable) genetic abnormalities (familial hypercholesterolemia), family history, increasing age, male gender, ○ (Modifiable) Hyperlipidemia, increased LDL, HTN. smoking, DM, inflammation. ○ Hyperhomocysteinemia associated with risk prediction. ○ Lipoprotein a [Lp(a)] is an altered form of LDL that contains the apolipoprotein B-100 portion of LDL linked to apolipoprotein A (apo A); Lp(a) levels are associated with coronary and cerebrovascular disease risk, independent of total cholesterol or LDL levels. Hallmark s/s: ○ stenosis, ischemic injury, chest pain with exertion due to 70-7% decrease in luminal cross-sectional area. Thrombus formation. Diagnostics: ○ CRP is an acute phase reactant synthesized primarily by the liver. Now being used for dx risk. LDL levels, Lp(a) levels, genetic testing. Complications/Secondary Conditions: ○ Increases risk of MI 5 fold (ages 40-60). CVA, Aortic aneurysm, PVD. See pics for plaque progression and outcomes. Hypercholesterolemia: (not a subsection but directly related to CAD/athero so adding it separately) ○ Patho: Lipids are transported in the bloodstream through specific apoproteins. Dyslipoproteinemias are lipoprotein abnormalities in the general population. i. Increased LDL, decreased HDL, increased levels of abnormal Lp(a) ○ Risk factors: resulting from mutations in apoproteins or lipoprotein receptors due to nephrotic syndromes, alcoholism, hypothyroidism or DM. ○ Hallmark:  ○ Dx: ○ Complications: leads to atherosclerosis, the dominant lipids in plaque is cholesterol and cholesterol esters. 3. Types and stages of shock Types of shock excluding anaphylactic *** I have a note that says Low CO with high preload with cardiogenic shock highlighted**** 4. Types of Heart Block Differentiate types of arrhythmias and the mechanisms behind their development Sick sinus syndrome. If the SA node is damaged, other fibers or even the AV node can take over pacemaker function, albeit at a much slower intrinsic rate (causing bradycardia).​ Atrial fibrillation. If the atrial myocytes become “irritable” and depolarize independently and sporadically (as occurs with atrial dilation), the signals are variably transmitted through the AV node, leading to the random “irregularly irregular” heart rate.​ Heart block. If the AV node is dysfunctional, varying degrees of heart block occur, ranging from simple prolongation of the P-R interval on electrocardiogram (first-degree heart block), to intermittent transmission of the signal (second-degree heart block), to complete failure (third-degree heart block).​ Genetic and heritable conditions play a role in disease development in some patients​ *** I have a note that says SVT override SA node *** 5. Myocarditis Myocarditis Primary Patho: Inflammatory disorder of the heart muscle characterized by necrosis and degeneration of myocytes Risk Factors: Hallmark s/s: fatigue, dyspnea, palpitations, precordial discomfort, and fever. The clinical features of myocarditis can mimic those of acute MI Diagnostics: Myocarditis, or inflammation of the heart muscle, can be difficult to diagnose because of its nonspecific symptoms. EKG, ECHO, chest x-ray, MRI Complications/Secondary Conditions: Myocarditis can interfere with heart function, and the heart muscle can be permanently damaged. Scar tissue may form as a result of the inflammation and interfere with heart function, plus increase the risk for abnormal heart rhythms. However, myocarditis doesn't always cause permanent damage to the heart 6. Thrombosis Formation Thrombus formation Primary Patho: ○ Stasis or turbulence: i. Promote endothelial activation, enhancing procoagulant activity and leukocyte adhesion, in part through flow-induced changes in the expression of adhesion molecules and pro-inflammatory factors  ii. Disrupt laminar flow and bring platelets into contact with the endothelium iii. Prevent washout and dilution of activated clotting factors by fresh flowing blood and the inflow of clotting factor inhibitors ○ Hypercoagulability: i. Either primary (e.g., factor V Leiden, increased prothrombin synthesis, antithrombin III deficiency) or secondary (e.g., bed rest, tissue damage, malignancy, or development of aPL antibodies [antiphospholipid antibody syndrome]) or antibodies against PF4/heparin complexes [heparin-induced thrombocytopenia]) ii. Thrombi may propagate, resolve, become organized, or embolize. iii. Thrombosis causes tissue injury by local vascular occlusion or by distal embolization. Risk Factors: ○ Primary abnormalities that lead to thrombosis are the so-called Virchow triad: i. (1) endothelial injury: by toxins, hypertension, inflammation, or metabolic products and is associated with endothelial activation and changes in endothelial gene expression that favor coagulation which leads to platelet activation. ii. (2) stasis or turbulent blood flow: Underling thrombus formation in the heart and the arterial circulation, where the high rate of blood flow impedes clot formation. iii. (3) hypercoagulability of the blood: Cardiac and arterial clots are typically rich in platelets, and it is believed that platelet adherence and activation is a prerequisite for thrombus formation under high shear stress, such as exists in arteries ○ Decreased blood flow in the setting of prolonged immobilization is the most common cause of lower extremity deep venous thrombosis (DVT); account for more than 90% of cases Hallmark s/s: ○ Depending on location of thrombus. Migratory thrombophlebitis (Trousseau syndrome) appears in one location then disappears to another. ○ local manifestations including vein dilation, edema, cyanosis, heat, erythema, or pain may be entirely absent, especially in bedridden patients ○ pain can be elicited by pressure over affected veins, squeezing the calf muscles, or forced dorsiflexion of the foot (Homan sign); Diagnostics: ○ US of lower extremities Complications/Secondary Conditions: ○ Pulmonary Emboli, CVA, MI 7. Aneurysm Aneurysm *** I just have a drawing around the true aneurysm bulging out bilaterally *** Patho: ○ Aneurysm: A localized abnormal dilation of a blood vessel or the heart, either congenital or acquired. ○ True aneurysm: Involves all the layers of an intact but weakened arterial or ventricular wall (e.g., atherosclerotic, congenital vascular aneurysms, or those post-myocardial infarction). ○ False aneurysm (pseudoaneurysm): A defect in the vessel wall leads to a hematoma that communicates with the intravascular space. ○ Dissection: Blood enters the vessel wall, separating its layers, and can result from a tear or rupture of the vasa vasorum. Risk Factors: ○ Atherosclerosis,Congenital conditions, Transmural myocardial infarctions (for ventricular aneurysms) Hallmark s/s:  ○ Saccular aneurysms: Spherical outpouching of a portion of the vessel wall; commonly 2 to 20 mm in intracranial vessels and 5 to 10 cm in the aorta. ○ Fusiform aneurysms: Diffuse, circumferential dilation of a long segment of a vessel, often 5 to 10 cm in the aorta and involving the aortic arch, abdominal aorta, or iliac arteries. Diagnostics: Complications/Secondary Conditions: Rupture of true or false aneurysms or dissections, often with catastrophic outcomes. Thrombosis in aneurysms, particularly in fusiform types. 8. Secondary HTN Patho: ○ Hypertension can occasionally be caused by single-gene disorders or can be secondary to diseases of the kidney, adrenal glands, or other endocrine organs. ○ Sustained hypertension requires the participation of the kidney, which normally responds by eliminating salt and water. ○ In established hypertension, both Secondary Hypertension increased blood volume and increased peripheral resistance contribute to the elevated blood pressure. Renovascular hypertension: Renal artery stenosis decreases ○ Histologically, hypertension causes glomerular flow and pressure, leading to increased BP. thickening of arterial walls due to hyaline deposits and, in severe cases, by the proliferation of Primary hyperaldosteronism: Common cause of secondary endothelial cells (ECs) or smooth muscle cells hypertension, either idiopathic or caused by aldosterone-secreting (SMCs) and basement membrane replication. adrenal adenomas. Risk Factors: single-gene disorders and secondary conditions affecting the kidney and Single-gene disorders: Rare, severe forms of hypertension due to gene endocrine system defects affecting aldosterone metabolism or sodium reabsorption (e.g., Hallmark s/s: Liddle syndrome). ○ ​Hypertension is typically asymptomatic until late in its course. Pheochromocytoma: ○ Malignant hypertension (5% of cases): Rapidly rising blood pressure (SBP > 200 mm Hg, Tumors of chromaffin cells that release catecholamines (and DBP > 120 mm Hg), often leading to renal failure, sometimes peptide hormones), causing hypertension. retinal hemorrhages, exudates, and possibly 90% of patients exhibit hypertension; two-thirds have papilledema. paroxysmal episodes with abrupt BP spikes, tachycardia, ○ Hypertensive emergency: A sudden, palpitations, headaches, sweating, and tremor. severe increase in BP with end-organ damage (e.g., Triggers for episodes: stress, exercise, posture changes, renal failure, retinal changes, cardiovascular events). tumor palpation, micturition (urinary bladder ○ Hypertensive urgency: Similar BP paragangliomas). elevation but without end-organ damage. Can lead to cardiac complications like congestive heart Diagnostics: failure, pulmonary edema, myocardial infarction, and ○ Monitor for severe pressure elevations ventricular arrhythmias due to catecholamine toxicity. and assess for signs of end-organ damage (renal Lab diagnosis: Increased urinary excretion of failure, retinal hemorrhages, cardiovascular catecholamines and metabolites (e.g., vanillylmandelic acid, complications). metanephrines). ○ Parenteral antihypertensive agents are Treatment: Surgical excision with adrenergic-blocking used in hypertensive emergencies, requiring ICU agents; multifocal lesions require long-term medication for monitoring. hypertension. ○ In hypertensive urgency, oral medications are used to reduce BP over 24-48 hours. Complications/Secondary Conditions: end organ damage ○ Renal failure, stroke, and heart disease. ○ Cardiovascular disease from atherosclerosis ○ Heart failure due to increased myocardial workload. ○ Kidney failure from glomerular damage. ○ Affects the microcirculation of the eyes, possibly causing retinal hemorrhages and exudates. ○ Increased pressure in cerebral vasculature can lead to hemorrhage. 9. Hypertrophic Cardiomyopathy Hypertrophic Clinical heterogeneous, genetic disorder characterized by myocardial hypertrophy, Cardiomyopathy poorly, compliant left ventricle myocardium leading to abnormal diastolic filling, and (in about ⅓ of cases) intermittent ventricular outflow obstruction. Reduced stroke volume because of a reduced chamber size and the reduced compliance of the massively hypertrophied left ventricle, Most commonly caused by mutations in any one of several genes that encode sarcomeric proteins Clinical Manifestations Exertional dyspnea Harsh systolic ejection murmur causes by the ventricular outflow obstruction High left ventricular chamber pressure, and frequently thick-walled Cardiomyopathy Primary cardiomyopathies involve predominantly the heart. They may be genetic or acquired (e.g., viral myocarditis, anthracycline cardiotoxic).​ Secondary cardiomyopathies have myocardial involvement as a component of a systemic or multiorgan disorder​ ​ Classified by cause or functional impairment​ ​ Functional classifications ​ Dilated​ Hypertrophic​ Restrictive *** I have highlighted Hypertrophic cardiomyopathy ***  Diseases of the Respiratory System 1. Hypersensitivity Pneumonitis Hypersensitivity pneumonitis (Extrinsic Allergic Alveolitis) Patho: a. Immunologically mediated interstitial lung disorder due to prolonged exposure to inhaled organic antigens. b. Pathological changes primarily affect the alveolar walls. Risk Factors: c. Farmer's lung: Exposure to dust from humid, warm, newly harvested hay permits the rapid proliferation of the spores of thermophilic actinomycetes. d. Pigeon breeder's lung (bird fancier's disease): Exposure to proteins from birds' serum, excreta, or feathers. e. Humidifier or air-conditioner lung: Caused by thermophilic bacteria in heated water reservoirs. f. Pet birds and moldy basements may also contribute. Hallmark s/s: g. Acute Phase: Fever, dyspnea, cough, and leukocytosis; symptoms appear 4-6 hours post-exposure and can last 12 hours to several days. h. Chronic Phase: Progressive fibrosis, dyspnea, and cyanosis; similar symptoms to other chronic interstitial diseases. Diagnostics: i. Chest X-ray: May show micronodular interstitial infiltrates. j. Pulmonary Function Tests (PFTs): Indicate an acute restrictive disorder. k. Histological Findings: Lymphocytic infiltration, non-necrotizing granulomas, interstitial fibrosis, and obliterative bronchiolitis in chronic cases. Complications/Secondary Conditions: l. Risk of progression to serious chronic fibrotic lung disease if exposure continues. m. Long-term complications may include respiratory failure and severe interstitial lung disease. 2. Atopic Asthma Differentiate the types of asthma *** I cannot remember what the right answer was about this question about the exercise induced or drug induced asthma and prostaglandin *** ATOPIC WAS THE ONLY SPECIFIED ONE NON-ATOPIC ASTHMA EXERCISE-INDUCED DRUG-INDUCED OCCUPATIONAL ATOPIC ASTHMA ASTHMA ASTHMA ASTHMA Resp infections due to viruses Common in children and Aspirin-sensitive Triggered by: fumes IgE-mediated (Type I) (e.g., rhinovirus, parainfluenza adolescents asthma is an (epoxy resins, plastics) hypersensitivity reaction virus, and RSV) are common uncommon type Bronchospasm often occurs Organic and chemical Usually begins in childhood and is triggers in non-atopic asthma. dusts (wood, cotton, within 3 minutes after the end Occurs in individuals triggered by environmental Inhaled air pollutants such as of exercise; usually resolves in with recurrent rhinitis platinum) allergens, such as dusts, pollens, tobacco smoke, sulfur dioxide, 60 minutes and nasal polyps. cockroach or animal dander, and ozone, and nitrogen dioxide may Typical symptoms include Exquisitely sensitive to Gases (toluene) foods also contribute to the chronic dyspnea, wheezing, cough, aspirin and NSAIDs Other chemicals PATHOGENESIS airway inflammation and chest tightness, excessive Triggers asthmatic (formaldehyde, hyperreactivity in some cases. mucus production Caused by a Th2-mediated IgE attacks and urticaria. penicillin products) response to environmental In some instance's attacks may Heat loss, water loss, and Trigger asthma by Often have positive skin allergens in genetically be triggered by seemingly increased osmolarity of the inhibiting the test reactions to protein predisposed individuals innocuous events, such as lower respiratory mucosa cyclooxygenase pathway allergens in the work exposure to cold and even stimulate mediator release Airway inflammation causes airway of arachidonic acid environment exercise. from basophils and tissue dysfunction through the release of metabolism, leading to mast cells causing smooth Tends to have potent inflammatory mediators and a rapid decrease in muscle contraction progressively more partly through remodeling of the prostaglandin E2 severe attacks with airway wall. Running, jogging, and tennis subsequent exposures are the most common As the disease becomes more stimulators Trigger Type I severe, there is increased local hypersensitivity secretion of growth factors, which reactions induce mucous gland enlargement, smooth muscle proliferation, Sensitization is angiogenesis, and fibrosis. ineffective treatment 3. Atelectasis Atelectasis- Differentiate types -Atelectasis is a condition where part or all of a lung collapses due to a blockage in the air passages or pressure on the lung. - Primary Patho: is caused by increased external pressure on the lung - Resorption atelectasis - occurs when oxygen and carbon dioxide in the alveoli move into the bloodstream, causing the alveoli to collapse. - Intrathoracic tumors, mucous plugs, and foreign bodies can partially or completely block airways. Children are particularly susceptible due to their less-developed collateral ventilation pathways. Conversely, adults with chronic obstructive pulmonary disease (COPD), who have extensive collateral airways, are less likely to develop obstructive atelectasis - Compression atelectasis - is caused by increased external pressure on the lung - Pleural effusions, pneumothorax, abdominal distension, or tumors may cause compression at