Pathophysiology: Concepts Assessment 1

Inflammation can be either acute or chronic. The immune system is thought to play a role in chronic inflammation and may be one of the reasons chronic inflammation may persist for days to months to years. Why is the risk of scarring and deformity greater in chronic inflammation than it is in acute inflammation?

Fibroblasts instead of exudates proliferate in chronic inflammation.

Which are the main endogenous pyrogens that act on the hypothalamus?

IL-1 and TNF

Sylvia Lewis is a 62-year-old woman, who has smoked cigarettes most of her adult life. She notices that she is more prone to respiratory tract infections. What type of cellular changes occur in the pulmonary airways when the ciliated columnar epithelial cells that are exposed to the chronic irritation of cigarette smoke are replaced by stratified squamous epithelial cells?

Metaplasia

Jane Doe is a 45 y/o woman, who has been receiving radiation therapy for breast cancer. Check all true statements.

-Because the injurious effects of ionizing radiation vary with the dose, fractionated doses given at intervals reduce the exposed tissues to irreversible radiation injury. -Endothelial cells in blood vessels are particularly sensitive to irradiation, therefore, immediately after irradiation, the initial erythema of the skin results from vessel dilatation. -Ionizing radiation can immediately kill cells, interrupt cell replication, or cause genetic mutations. -Ionizing radiation is used in destruction of cancer cells causing ionization of molecules and atoms in cells by either directly hitting target molecules in the cell or by producing free radicals that interact with critical cell components.

Free radicals form in cells as a product of mitochondrial respirations as reactive oxygen species (ROS). What do you know about free radicals? Select all true statements.

-Free radicals are a reactive chemical species with an unpaired electron in the outer orbit of the molecule causing a chain reaction that creates new free radicals. -Free radicals react with proteins, lipids, and carbohydrates resulting in damage to the cell membrane, inactivation of enzymes, and damage to DNA. -Oxidative stress from free radicals results when the generation of ROS exceeds the ability of the body to eliminate and neutralize these reactive chemical species. -Antioxidants, occurring as endogenous enzymes or ingested from supplements or food sources, inhibit the reactions of ROS.

About 50% of males over age 60 develop benign prostatic hyperplasia as a result of the excessive release of androgens. The hyperplasia may increase to such an extent that the prostate, which encircles the urethra, can cause urethral narrowing resulting in a slow or weak urine stream, hesitancy in starting urine flow, and frequent urge to urinate. What are the characteristics of hyperplasia? Select all correct responses.

-Hyperplasia can only occur in cells capable of mitotic division. -Physiologic hyperplasia occurs in response to a stimulus and ends after the stimulus is removed; i.e., removal of the stimulating hormone. -Cellular hyperplasia is an increase in the number of cells in an organ or tissue. -Cellular hyperplasia occurs when there is activation of the genes controlling cell proliferation and the intracellular messengers that control cell replication and growth.

What are the causes of intracellular accumulations? Select all that apply.

-Inability of cell to metabolize an endogenous product due to blockage of a metabolic pathway. -Rate of cellular metabolism inadequate to remove excess of normal cell products. -Environmental agents that cannot be metabolized and removed from the cell.

Upon chest x-ray, it was noted that a 36-year-old woman, who was exposed to tuberculosis had several small lesions in her lung due to granulomatous inflammation. What are the characteristics of granulomas? Select all correct responses.

-Several conditions may cause granulomatous inflammation including splinters, sutures, silica, asbestos, syphilis, sarcoidosis, deep fungal infections, brucellosis, and TB. -Granulomas are 1-2 mm lesions resulting from the amassing of macrophages surrounded by lymphocytes. -Epithelioid cells clump forming a multinucleated giant cell by surrounding the foreign agent, which is then encapsulated by connective tissue; often termed foreign body giant cells.

Darrell Johnson is a 30 year-old man, who sustained a fracture of his left tibia 2 months ago. The cast has just been removed, and he is amazed at the degree to which the muscles in his leg have shrunk. What are the reasons for this muscle cell atrophy? Select all correct responses.

-The muscle cell atrophy is adaptive and reversible. -The muscle cell atrophy is a physiological response to due to disuse. -The muscle cell size is reduced due to a decrease in the usual workload demand.

During the inflammatory process, arachidonic acid metabolites ________ (select all that apply).

-activate the cyclooxygenase pathway, which induces inflammation and potentiates the effects of histamine and other inflammatory mediators. -activate the lipoxygenase pathway, which synthesizes leukotrienes and complements the action of histamine.

During the inflammatory process, cytokines and chemokines _______ (select all that apply).

-are activated by TNF-alpha and IL-1 when stimulated by bacterial toxins, immune cells, injury, and other inflammatory stimuli. -cause priming and aggregation of neutrophils. -cause endolithial cells to express adhesion molecules.

Oxidative stress resulting from exposure to high levels of ROS has been implicated as the causative agent in numerous disease states as well as the cause of physiological aging. Select all true responses that describe how oxidative stress affects cells.

-changes gene expression; e.g. mutations in the gene for SOD that is associated with ALS. -causes oxidation of cellular components resulting in cell injury and tissue damage. -causes endothelial dysfunction resulting in cardiovascular disease.

Injurious agents (e.g., heat, genetic-causing metabolic disturbances, or altered immune responses) exert negative effects on the cell. What are the mechanisms that can result in cell injury or death? Mark all that apply.

-hypoxia or ischemia -free radical formation -impaired calcium homeostasis

Select all systemic manifestations of inflammation in the acute-phase response.

-leukocytosis and, in severe infections, bone marrow production of immature neutrophils to keep up with the inflammatory response. -liver increases synthesis of protective and defense proteins - including fibrinogen, C-reactive protein, and serum amyloid A. -response results from a bacterial sepsis. -may progress to uncontrolled inflammatory response with production and release of inflammatory cytokines causing SIRS that can lead to circulatory shock.

Plasma-derived mediators include (select all that apply):

-proteins of the complement system that 1) cause vasodilation and increased vascular permeability; 2) promote leukocyte activation, adhesion, and chemotaxis; and 3) augment phagocytosis. -kinins that increase capillary permeability. -fibrinolysis system that contributes to the vascular phase and produces fibrin products during the final steps of clotting.

The cellular stage of acute inflammation is marked by changes in the endothelial cells. Number the sequence of events (1-4 with "1" being the first event) in which signaling between leukocytes and endothelial cells define the inflammatory event.

1. Capillary blood flow slows near the site of injury and cytokines trigger intercellular adhesion molecules to tether leukocytes to the endothelium. 2.Endothelial cells separate and leukocytes extend pseudopodia in order to travel through the capillary wall. 3.Leukocytes are guided by chemokines, bacterial and cellular debris, and complement fragments to the site. 4.Neutrophils, monocytes, and tissue macrophages engulf, degrade, and destroy bacteria and cellular debris.

Match the following examples of cell injury to the causative agent.

1. Infection with a virus: biological agent 2. Allergic reaction to penicillin: immunologic reaction 3. Frostbite: physical agents 4. disruption of intracellular bonds causing increased risk of skin cancer: radiation injury 5. Electric shock: physical agent 6.Adverse drug reaction: chemical agent 7. Congenital malformation due to chromosomal abnormality: genetic derangement 8. Protein-calorie starvation: nutritional imbalance

The cardinal signs of inflammation result from the physiologic process of the inflammatory cells and protein systems. Match the sign to its causative explanation.

1. increased permeability of blood vessels due to histamine and other long-term vasoactive mediators causing accumulation of blood in the extravascular space: swelling (tumor). 2. fluid accumulation into the tissues and the release of bradykinin, prostaglandins, and histamine stimulating the sensory nerve endings: pain (dolor). 3. increased blood flow due to histamine release causing dilation of small blood vessels in area: redness (rubor). 4. increased perfusion in peripheral tissues due to vasodilation at the wound site and flow of warm blood into the area: heat (calor).

Match the pathologic term to its correct descriptor.

1. occurs in normal tissues as the result of increased serum calcium levels: Metastatic Calcification. 2. oxygen-containing molecules that are highly reactive: Reactive Oxygen species (ROS). 3. Natural & synthetic molecules that inhibit the reactions of ROS with biological structures: Antioxidants. 4. Programmed cell death: Apoptosis. 5. Macroscopic deposition of calcium salts in injured tissue: Dystrophic Calcification. 6. Ice crystal formation in cytosol: Temperature-induced Injury. 7. Impaired oxygen delivery: Ischemia. 8. dead cells persist indefinitely as soft cheeselike debris: Caseous Necrosis. 9. causes injury by changes in electron stability: ionizing radiation. 10. Term applied when a considerable mass of tissue undergoes necrosis: gangrene.

There are several cell types involved in the inflammatory process. Match the cell type to its descriptor(s) - there may be more than one match per descriptor.

1. produce antiplatelet and antithrombotic agents to regulate vessel patency and blood flow: Endothelial cells. 2. small membrane-bound disks circulating in blood that release inflammatory mediators to increase vascular permeability and alter chemotactic, adhesive, and proteolytic properties of endothelial cells: Platelets. 3. provide selective permeability barrier to exogenous and endogenous inflammatory stimuli: Endothelial cells. 4. scavenger cells with cytoplasmic granules containing enzymes and other antibacterial substances (short life span of 24-48 hours): Neutrophils. 5. participate in allergic reactions by controlling release of chemical mediators; may also be present in chronic inflammation: Eosinophils.

There are several cell types involved in the inflammatory process. Match the cell type to its descriptor(s). There may be more than one match to a cell type.

1. produce cytokines to activate macrophages and increase antigen presentation and cytokine production: Lymphocytes & plasma. 2. contain cell family adhesion molecules; selectins, integrins, and the immunoglobulin superfamily that mediate leukocyte recruitment: Extracellular matrix. 3. provide vasoactive mediators that produce prostaglandins, leukotrienes, PAF, inflammatory cytokines and growth factor: Connective tissue cells- monocytes & macrophages. 4. granulocytes that bind IGE; release histamine and vasoactive agents from granules: Basophils/mast cell. 5. develop plasma cells and produce antibodies against persistent antigens at the inflammatory or altered tissue site: Lymphocytes & plasma.

Apoptosis regulates certain cells by balancing proliferation and cell death, selectively eliminating injured and aged cells, and controlling regeneration. There are 2 apoptotic pathways: extrinsic and intrinsic. Match the processes to the correct pathway.

Apoptosis extrinsic pathway: -extracellular signaling proteins, TNF and Fas ligand, trigger apoptosis. -death cell receptor dependent. -Fas ligand binds to its receptor forming the death-initiating complex by converting procaspase-8 to caspase-8 and activating endonucleases that cause DNA fragmentation. Apoptosis intrinsic pathway: -death cell receptor independent. -triggered by DNA damage with activation of p53 protein, ROS, hypoxia, decreased ATP, or cellular senescence. -Bc12 protein regulators insert into the mitochondrial membrane opening channels for protein release into the cytoplasm. -mitochondria releases cytochrome c into the cytoplasm resulting in binding to caspace-3 allowing for bridging of the pathways and activation of caspase-8.

Children >6 years of age that are exposed to lead in the environment may develop growth and intellectual retardation. Lead poisoning results from ______.

Exposure to lead over a period of time causing an abnormal accumulation of this exogenous substance in the body cells including nerve cells, which affects nerve transmission and brain development

Reversible or irreversible: A man has a heart attack with necrosis of a portion of the myocardium due to prolonged anoxia.

Irreversible Accumulation

Reversible or irreversible: An infant has a genetic disorder causing gangliosidosis - build up of glycolipids in the central nervous system neurons. There is progressive destruction of the neurons in the CNS.

Irreversible Accumulation

Reversible or irreversible: An infant with erythroblastosis fetalis develops kernicterus resulting in severe central nervous system injury.

Irreversible Accumulation

A woman develops a blockage of the common bile duct and she develops jaundice - noted first in the white of the eyes (sclera). The blockage is relieved with removal of the gallbladder and gallstones.

Reversbile Accumulation

Reversible or irreversible: A man has atherosclerosis with >1.5 mm blockage in a coronary artery. A stent is placed in the artery to relieve the blockage. He follows his doctor's instructions for a diet and exercise regimen and takes a cholesterol-lowering drug.

Reversible Accumulation

Reversible or irreversible: A woman is diagnosed with type 2 diabetes mellitus with fatty accumulations in the liver cells. She institutes the prescribed oral anti-diabetic drug and diet and exercise changes. At the most recent doctor visit, both her weight and blood sugar level are within normal ranges.

Reversible Accumulation

There are 2 stages in the acute inflammatory response that act to remove the injurious agent and limit the extent of tissue damage. Contrast these stages by matching the activities to the correct stage of the acute inflammatory process.

Vascular Stage: -extravasation of exudate, RBCs, leukocytes, platelets, and clotting factors into the extravascular spaces causing swelling, pain, and impaired function. -vasodilation of arterioles and capillary beds at the site of injury causing erythema and warmth. -response patterns include immediate-transient in minor injuries; immediate-sustained in severe injury; and delayed-hemodynamic in radiation injury. Cellular Stage: -chemotactic cytokines direct leukocytes to site of early inflammation/injury. -leukocytes slow migration, adhere to endothelium, and move along periphery of blood vessels. -neutrophils, monocytes, and tissue macrophages engulf and degrade bacteria and cellular debris. -endothelial cells separate, extend pseudopodia and cross through the vessel wall.