Final Exam Flashcards
What is the definition of “pathophysiology”?
Pathophysiology is defined as not only the cellular and organ changes that occur with disease, but also the effects that these changes have on total body function.
Name the 5 etiologic factors and give an example if listed.
Biologic agents (bacteria, viruses), physical forces (trauma, burns, radiation), chemical agents (poisons, alcohol), one’s genetic inheritance, and nutritional excesses or deficiencies.
What are the 2 types of risk factors?
Risk factors can be categorized as congenital conditions (present at birth) or acquired defects (occurring after birth).
What is the difference between morphology and histology?
Morphology is defined as the fundamental structure or form of cells or tissues. Histology is the study of the cells and extracellular matrix of body tissues.
Describe the difference between signs and symptoms and give an example of each.
A symptom is a subjective complaint, for example pain, trouble breathing, or dizziness. A sign is an objective manifestation, for example an elevated temperature, a swollen extremity, or changes in pupil size.
What are 3 important processes when coming to a diagnosis?
The diagnostic process requires a careful history, physical examination (PE), and sometimes diagnostic tests.
Explain validity, reliability, sensitivity, and specificity.
Validity is how a tool measures what it is intended to measure. Reliability is how likely the same result will occur if repeated. Sensitivity is the proportion of people with a disease who are positive for that disease. Specificity are people without the disease who are negative on a given test.
Define epidemiology and name some things that it tracks.
Epidemiology is the study of disease occurrence in human populations. It tracks age, race, dietary habits, lifestyle, or geographic location.
What is the difference between incidence and prevalence?
Incidence is the number of new cases in a population at risk during a specified time. Prevalence is the number of people with the disease in a population in a given time.
Define mortality and morbidity.
Morbidity is the effect of an illness on one’s life. Mortality statistics deal with the cause of death in a population.
Define primary, secondary, and tertiary prevention and give an example of each.
Primary prevention is to remove risk factors to prevent disease from occurring- taking folic acid while pregnant to prevent neural tube defects, vaccinating children to prevent communicable disease, eating healthy and exercising to prevent heart disease, and wearing seatbelts or helmets. Secondary prevention aims to detect and treat disease early, usually while the disease is asymptomatic and curable- annual Pap smears to detect early cervical cancer, encouraging smoking cessation, checking blood pressure and cholesterol, and colonoscopy screening. Tertiary prevention occurs after a disease has been diagnosed and clinical intervention is needed to reduce complications or deterioration- certain medications one must take after a heart attack to help reduce the risk of a future event or death.
Why is evidence-based practice important?
Evidence-based practice is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. This is to counteract “the way things have always been done,” and to practice based on clinical research.
What are the 3 primary structures of the cell?
All eukaryotic cells have three primary structures that are considered the functional components of the cell. These are the nucleus, the cytoplasm, and the plasma membrane.
What is the function of the nucleus?
The nucleus is the control center for the cell and contains most of the hereditary material, DNA and RNA.
Name 3 structures within the nucleus.
Chromatin, nucleolus, and nuclear envelope
What organelles are located in the cytoplasm?
The organelles in the cytoplasm include the ribosomes, ER, Golgi complex, mitochondria, and lysosomes.
What are the roles of the ribosomes, rough ER, and smooth ER?
The ribosomes are the site of protein synthesis in the cell. The Rough ER has ribosomes and functions to synthesize lysosomal enzymes. The smooth ER does not have ribosomes and is the site for lipid, lipoprotein, and steroid hormone synthesis.
What is the function of the lysosomes, peroxisomes, and mitochondria?
Lysosomes are the digestive system of the cell. Peroxisomes are smaller than lysosomes and function in the control of free radicals. The mitochondria are aptly termed the “power plants” of the cell, as they transform organic compounds (energy in food) into cellular energy for the cell.
What is contained in the cytoskeleton and what is its function?
The cytoskeleton contains a network of microtubules, microfilaments, intermediate filaments, and thick filaments. They control cell shape and movement.
Give examples of where cilia and flagella are found in the human body.
Cilia can be found on many epithelial linings, including the nasal sinuses and bronchi in the upper respiratory system. In the human body, only spermatozoa contain flagella.
What are the 4 functions of the cell membrane?
The cell membrane controls the transport of materials from the outside fluids to within, binds hormone receptors, helps with the conduction of electrical currents in nerve and muscle cells, and aids in the regulation of cell growth and proliferation.
Why do cells need to communicate with one another?
In complex organisms, cells develop special functions, contribute to growth, and adapt to changes. Cells must have the ability to communicate with one another, transport substances in and out, and respond to these changes.
Name the 4 types of cell signaling.
Endocrine signaling - hormones carried in the bloodstream to act on cells throughout the body.
Paracrine signaling - enzymes metabolize chemical mediators, producing a change in neighboring cells.
Autocrine signaling - a cell releases a chemical into the extracellular fluid that affects its own activity.
Synaptic signaling - occurs in the nervous system as neurotransmitters act on adjacent nerve cells through synapses.
Know the process of up and down regulation.
Every cell has a distinct set of surface receptors that allow it to respond to signaling molecules in a specific way. These proteins can increase or decrease in number according to the needs of the cell. When there are too many chemical messengers present, the number of active receptors decreases in a process called down-regulation. When the messengers are lacking, the number of active receptors increases through up-regulation.
Explain diffusion, facilitated diffusion, and active transport.
Diffusion is the process by which electrolytes move from an area of higher concentration on one side of the membrane to an area of lower concentration on the other side. Facilitated diffusion uses a transport protein to help lipid insoluble or large molecules pass through the membrane, that otherwise would not be able to get through. Active transport is used when cells use energy to move ions against an electrical or chemical gradient.
What is the most important active transport system and why is it important?
The most studied active transport system is the sodium-potassium (Na+/K+)-ATPase pump. The pump moves sodium from inside the cell to the extracellular region and returns potassium to the inside of the cell. If this process didn’t occur, sodium would remain in the cell and water would follow, causing the cell to swell.
Define endocytosis and the 2 processes it encompasses.
Endocytosis is when a molecule outside of a cell is enclosed in an invagination of the cell membrane, forming a vesicle inside the cell. Pinocytosis (“cell drinking”) engulfs small solid or fluid particles like proteins and electrolytes. Phagocytosis (“cell eating”) is when the membrane engulfs and then kills microorganisms or other particulate matter. When the particle is enclosed, a phagosome is formed which is moved into the cytoplasm, where it joins with a lysosome to be destroyed.
Why are ion channels necessary?
Because small ions like sodium and potassium have an electrical charge, they are unable to get through the lipid layer of the cell membrane. Their way across is by facilitated diffusion through selective ion channels.
Understand the different types of transport systems.
n primary active transport, ATP is used directly to transport the substance. In secondary active transport, energy is derived from the primary active transport of one substance, usually sodium, for the cotransport of a second substance. When sodium leaves the cell by primary active transport, a concentration gradient develops. This results in storage of energy because sodium is wanting to diffuse back into the cell. Two groups of secondary active transport are available. Cotransport or symport systems consist of sodium ions and the solute being transported in the same direction. Counter-transport or antiport systems has sodium ions and the solute being transported in the opposite direction. An example of cotransport occurs in the intestine in which the absorption of glucose and amino acids is paired with sodium transport.
What are membrane potentials?
Electrical potentials that exist in the cell membrane are called membrane potentials. Membrane potentials in nerve and muscle cells are needed to generate nerve impulses and muscle contractions. In other cells, changes in the membrane potential can cause hormone secretion.
Be familiar with the 4 different types of tissue and characteristics of each.
Epithelial tissue covers the body’s outer surface, lines the inner surfaces, and forms glandular tissue. The basal surface is attached to an underlying basement membrane, it is avascular and draws oxygen and nutrients from the capillaries of the connective tissue on which it rests. Epithelial tissues can be squamous, cuboidal, and columnar. They can be arranged in simple, stratified, and pseudostratified layers.
Connective tissues produce extracellular matrix that supports and holds tissues together. Connective tissue proper include loose (areolar), adipose, reticular, and dense connective tissue. Specialized connective tissue includes cartilage, bone, and blood cells.
Muscle tissues move the skeletal structures, pump blood through the heart, and contract the blood vessels and visceral organs. THe fibers that produce muscle tissue contraction are thin filaments called actin and thick filaments called myosin. Muscle tissue can be skeletal, cardiac, or smooth.
Nervous tissue is used for communication between peripheral tissues and the central nervous system. It provides the means for controlling body function and for sensing and moving about the environment in response to internal and external stimuli. The two types of nervous tissue cells are neurons (communication) and glial cells (support the neurons).
What is atrophy and what causes it?
Atrophy is a decrease in the size of an organ or tissue resulting from a decrease in the mass of pre-existing cells. It’s typically a result from disuse, nutritional or oxygen deprivation, diminished endocrine stimulation, aging, and denervation (lack of nerve stimulation in peripheral muscles caused by injury to motor nerves).
Know the difference between hypertrophy and hyperplasia.
Hypertrophy is the increase in the size of an organ or tissue due to the increase in the size of the cells that comprise it, often related to workload.
Hyperplasia is the increase in the size of an organ or tissue caused by an increase in the number of cells making up that organ or tissue.
What is the advantage and disadvantage of metaplasia?
Metaplasia usually occurs in response to chronic irritation and inflammation and allows for substitution of cells that are better able to survive under those circumstances. Under persistent stress, it can progress to dysplasia.
Define dysplasia. Is it reversible? What can it lead to?
Dysplasia is disordered cellular growth and can result in cells that vary in size, shape, and organization. Dysplasia is reversible, in theory, with alleviation of inciting stress. If stress persists, dysplasia progresses to carcinoma (irreversible).
List the 5 categories in which cells can be damaged and give an example of each.
Cells can be damaged by the following: (1) Injury from physical agents (mechanical forces [fractures], extremes of temperature [burns], and electrical forces); (2) Radiation injury (ionizing [cancer treatment], ultraviolet [sunburn], or nonionizing [thermal burns] radiation.); (3) Chemical injury (drugs [alcohol, Rx/OTC drugs, street drugs], carbon tetrachloride, lead toxicity, and mercury toxicity.); (4) Injury from biologic agents (viruses, parasites, and bacteria); and (5) Injury from nutritional imbalances (excess or a deficiency).
What is apoptosis?
Apoptosis is programmed cell death that eliminates cells that are worn out, have been produced in excess, developed improperly, or are genetically damaged.
Know the different types of necrosis.
Coagulative necrosis is often from a sudden cutoff of blood supply to an organ. Liquefactive necrosis occurs when some of the cells die but their catalytic enzymes are not destroyed. Caseous necrosis is part of granulomatous inflammation and often associated with tuberculosis. Gangrenous necrosis is when a significant amount of tissue undergoes necrosis and can be characterized as either dry or moist.
What are the three types of cell injury?
Free radical formation - free radicals are highly reaction making them unstable, enabling them to disrupt and damage cells and tissues.
Hypoxia - hypoxic cell injury is due to low oxygen delivery to the tissues. Decreased oxygen impairs oxidative metabolism, resulting in the decreased production of ATP (energy), which leads to cellular injury as necessary metabolic processes cannot be efficiently carried out.
Disruption of intracellular calcium homeostasis - calcium functions as a second messenger for many cell reactions. Usually intracellular calcium levels are lower than extracellular levels, thus a rise in intracellular calcium can inappropriately activate enzymes leading to potentially damaging effects.
During pregnancy, uterine enlargement is caused by what?
Hypertrophy and hyperplasia.
Persistent dysplasia eventually results in….
cancer.
Is endometrial hyperplasia a normal physiologic occurrence?
No
A patient complains of chest pain and an elevated blood pressure. What are these examples of?
Signs & symptoms
Explain apoptosis and why it is necessary:
Apoptosis is programmed cell death. This process eliminates cells that are worn out, have been produced in excess, have developed improperly, or have genetic damage. Apoptosis is also responsible for several normal physiologic processes, like replacing cell in the intestinal villi and removing aging red blood cells.
Explain what necrosis is and give an example and description of one type of necrosis.
Necrosis refers to cell death in an organ or tissues that is still part of a living person. It often interferes with cell replacement and tissue regeneration. Coagulative necrosis results most often from a sudden cutoff of blood supply to an organ (ischemia), particularly the heart and kidney. Liquefactive necrosis occurs when some of the cells die but their catalytic enzymes are not destroyed. It is commonly seen with brain infarcts or abscesses. Caseous necrosis occurs as part of granulomatous inflammation and is most often associated with tuberculosis.
Gangrenous necrosis most often affects the lower extremities or bowel and is secondary to vascular occlusion. The term gangrene is applied when a considerable mass of tissue undergoes necrosis. In dry gangrene the affected tissue becomes dry and shrinks, the skin wrinkles, and its color changes to dark brown or black. The spread of dry gangrene is slow. It results from a cut off in arterial blood supply and is a form of coagulation necrosis. In wet gangrene, the affected area is cold, swollen, and pulseless. The skin is moist, black, and under tension. Blebs form on the surface, liquefaction occurs, and a foul odor is caused by bacterial action. The spread of tissue damage is rapid.
List the 4 types of tissue found in the body. Pick 2 and give a description and example of each.
Epithelial tissue covers the body’s outer surface, lines the inner surfaces, and forms glandular tissue. Epithelial tissue has three distinct surfaces and the basal surface is attached to an underlying basement membrane. It is avascular, meaning without blood vessels. It receives oxygen and nutrients from the capillaries of the connective tissue on which it rests.
Connective or supportive tissue is the most abundant tissue in the body. It connects and binds or supports the various tissues. Its cells produce the extracellular matrix that support and hold tissues together. Connective tissue is divided into two types: connective tissue proper and specialized connective tissue (cartilage, bone, and blood cells). The four types of connective tissue proper are loose (areolar), adipose, reticular, and dense connective tissue.
The function of muscle tissue is to move the skeletal structures, pump blood through the heart, and contract the blood vessels and visceral organs. Muscle tissue can accomplish this by contraction. The two types of fibers that contract are called thin and thick filaments. Thin filaments are called actin, and the thick filaments are myosin. The three types of muscles tissue are skeletal, cardiac, and smooth.
Nervous tissue is distributed throughout the body for communication. It provides the means for controlling body function and for sensing and moving about the environment. The two types of cells are neuron and glial cells. Neurons function is communication. Glial (meaning glue) cells support the neurons.
What is the most studied active transport system in the human body?
The most studied active transport system in the human body is the sodium-potassium-ATPase active transport system that moves sodium out of the cell and potassium into the cell to prevent cells from swelling too much from water.
What term means “cell drinking,” and engulfs small solid or fluid particles, as seen with proteins and electrolytes?
Pinocytosis.
Give one function of a membrane potential:
Generate nerve impulse, muscle contractions, or cause hormone secretion
What is the term that best describes the following process?
A transport protein aiding a lipid insoluble or large molecule across the cell membrane that would otherwise not be able to pass through on its own.
facilitated diffusion
Define neoplasia and neoplasm:
Neoplasia is the process of unregulated growth of abnormal cells with patterns of altered cell differentiation and growth. A neoplasm is the new growth itself.
Define proliferation and differentiation:
Proliferation, a process of cell division, is an adaptive process for new cell growth to replace old cells or when additional cells are needed. Differentiation is the process in which cells become more specialized with each mitotic division.
What are the 3 main groups of cells that proliferate?
(1) well-differentiated neurons and cells of skeletal and cardiac muscles that rarely divide and reproduce; (2) progenitor or parent cells that continue to divide and reproduce, like blood, skin, and liver cells; (3) undifferentiated stem cells that can enter the cell cycle and produce large number of progenitor cells if needed.
What are progenitor cells?
The more specialized cells are unable to divide, so these cell populations rely on progenitor or parent cells of the same lineage that have not yet differentiated to the extent that they have lost their ability to divide. They have enough differentiation so the daughter cells are limited to the same cell line, but not quite differentiated enough to prohibit active proliferation.
What are the benefits of the stem cell?
Stem cells remain incompletely differentiated and dormant until they are needed. When they divide they produce other stem cells, but also cells capable of carrying out the functions of the needed differentiated cell (i.e. progenitor cells) until they reach a state of terminal differentiation.
Stem cells possess self-renewal, meaning they can undergo numerous mitotic divisions while maintaining an undifferentiated state, and they have different levels of potency - they can differentiate into different states.
What is a polyp?
A polyp is a growth that projects from a mucosal surface, such as the intestine. A polyp can be benign or malignant.
Explain metastasis and how it occurs:
Metastasis is when a secondary tumor develops in a distant location from the primary tumor. It occurs via the lymph channels and blood vessels. The cancer cell is shed from the primary tumor, it invades the surrounding extracellular matrix where it gains access to a blood vessel. If the cells survive the bloodstream, it has to invade tissue elsewhere, grow, and establish a blood supply as well as growth factors.
What are the two broad categories of malignant neoplasms?
Solid tumors and hematologic cancers
Explain what carcinoma in situ is?
Carcinoma in situ is a localized preinvasive lesion. These can typically be surgically removed or treated, and recurrence is less likely.
What is seeding?
Seeding is the process of how shed tumor cells enter circulation and move into similar or different body cavities. It often happens in the peritoneal cavity. It usually causes fluid accumulation.
What is important about the sentinel node?
The sentinel node is the first lymph node to which the primary tumor drains. Through lymphatic mapping and sentinel lymph node biopsy, the extent of the disease can be determined.
What is angiogenesis?
When the tumor reaches the distant site, it must establish blood vessels and growth factors to continue to grow. The development of new blood vessels within the tumor is termed angiogenesis.
What are the 2 broad etiologic causes of cancer?
The genetic and molecular mechanisms that transform normal cells into cancer cells.
The external factors such as age, heredity, and environmental agents.
What are the 2 cancer associated genes?
Proto-onocogenes which are normal genes that become cancer causing oncogenes if mutated. They are associated with gene overactivity.
Tumor suppressor genes slow down cell division, repair DNA mistakes, or tell cells when to die. They are associated with gene underactivity.
What are the 3 genetic events that lead to oncogene formation and activation?
Point mutation - there is a single nucleotide base change due to an insertion, deletion, or substitution.
Chromosomal translocation - the unusual movement or rearrangement of a segment of chromosomal DNA.
Gene amplification - the unusual increase in the number of copies of a certain gene. This leads to an unwanted over-expression of the gene. As the amount of proteins encoded by the gene drastically increases, the result is often an increase in cell proliferation.
What the 6 molecular and cellular mechanisms that are known to facilitate the development of cancer?
Genes that increase susceptibility to cancer include defects in DNA repair mechanisms, defects in growth factor signaling pathways, evasion of apoptosis, avoidance of cellular senescence, development of sustained angiogenesis, and metastasis and invasion.
What are the 7 risk factors that can lead to the development of cancer?
Risk factors linked to cancer include heredity, hormonal factors, obesity, immunologic mechanisms, environmental agents such as chemicals, radiation, and cancer-causing viruses.
Give an example of a hereditary cancer:
Breast cancer has been linked with BRCA1 and 2.
What organs do hormones and the development of cancer target?
Breast, ovary, endometrium, prostate
List some lifestyle factors that contribute to the development of cancer?
Smoking, alcohol consumption, eating red meat and meats that have been cooked over charcoal, low consumption of plants.
What are the 4 oncogenic viruses that can induce cancer?
Human Papilloma Virus (HPV) –> cervical cancer
EBV –> Burkitt lymphoma, nasopharyngeal cancer, B Cell lymphomas, and Hodgkin lymphoma
HHV-8 –> Kaposi Sarcoma
HBV –> liver cancer
List some common symptoms people with cancer have:
Bleeding, pleural/peritoneal fluid, anorexia, weight loss, wasting of body fat and muscle tissue, weakness, fatigue, sleep disturbances, anemia.
Why is anemia common in people with cancer?
Anemia is common because of the effects of the treatment or because of blood loss, hemolysis, or impaired red blood cell production.
What are paraneoplastic syndromes? Give an example.
Cancer can also produce symptoms in sites not directly affected by the disease. These manifestations are termed paraneoplastic syndromes. Examples are syndrome of inappropriate ADH secretion, Cushing syndrome due to ectopic ACTH production, and hypercalcemia.
What body parts do we screen through observation? Palpation? Laboratory tests and procedures?
Observation (skin, mouth, external genitalia), palpation (breast, thyroid, rectum and anus, prostate, lymph nodes), and laboratory tests and procedures (Pap smear, colonoscopy, mammography)
What are tumor markers helpful for?
Establishing prognosis, monitoring treatment, and detecting recurrent disease.
What is the most important procedure in diagnosing the correct cancer and histology?
Tissue biopsy
Define grading and staging and be familiar with table 2.5.
Grading is based on the cellular characteristics of the tumor and the degree of abnormalities present; it involves the microscopic examination of cancer cells to determine their level of differentiation.
Staging is the assessment of the clinical spread of the disease.
What is the purpose of grading and staging a tumor?
Both methods are used to determine the course of the disease and aid in selecting an appropriate treatment or management plan.
What are the 3 possible goals of cancer treatment?
Curative, control, and palliative
When is surgery appropriate in the treatment of cancer?
Surgery is appropriate to remove cancer, for diagnosing, staging, and palliation. This is determined by the extent of the disease, location, structures involved, tumor growth rate, and quality of life for the patient post-surgery.
If the tumor is small with well-defined margins; to treat oncologic emergencies; prophylactically
How does radiation kill cancer cells?
Radiation uses high energy particles or waves to destroy or damage cancer cells. It leads to the creation of free radicals which damage cell structures. It can interrupt the cell cycle process, kill cells, or damage DNA in the cells. It impacts all proliferating cells, but normal tissue is usually able to recover from the damage more readily than cancerous tissue.
List some side effects of chemotherapy drugs.
Neutropenia (risk for infections), anemia (Causing fatigue), thrombocytopenia (risk for bleeding)m anorexia, nausea, vomiting, alopecia.
List the 5 possible treatments for cancer:
Surgery, radiation therapy, chemotherapy, hormonal therapy, biotherapy.
Describe the cell cycle
The cell cycle is the process by which a cell duplicates its genetic information and divides between two genetically identical daugher cells. In Gap 1 - DNA synthesis stops while the cell enlarges and RNA and protein synthesis begins. S phase - DNA synthesis occurs, producing two separate sets of chromosomes, one for each daughter cell. Gap 2 - DNA synthesis stops again and RNA/protein synthesis continues. G1, S, G2 - interphase.
Between each phase are cell cycle checkpoints to ensure the cell is ready to proceed to the next phase, and if not, the cycle is halted and allowed to complete its replication or repair DNA damage if detected, ensuring all genetic information is passed on correctly. M Phase - mitosis (dividing the DNA) and cytoplasmic division.
Continually dividing cells (squamous epithelium) cycle from one mitotic division to the next, while some cells go into a resting state G0 if nutrients or growth factors are unavailable or highly specialized cells first leave the cell cycle. Cells in G0 may re-entre the cell cycle when nutrients become available. Highly specialized or terminally differentiated cells like neurons may stay permanently in G0.
What is the difference between benign and malignant tumors (table 2.2)
Benign cells are differentiated and similar to existing tissue; the growth rate is slow - it can stop growing or regress; the cells are non-invasive and usually encapsulated; they do not metastasize; and, they have a low mortality rate.
Malignant tumor cells are undifferentiated with atypical structure; the growth rate is variable - increased undifferentiation leads to more rapid growth rate; the cell growth is invasive and infiltrates surrounding tissues; the tumors are metastatic and use blood and lymphatic vessels to travel to distant sites; and they are associated with a high mortality.
Describe cancer cell characteristics (table 2.3)
Anaplasia - loss of cell differentiation in cancerous tissue. Highly anaplastic cells resemble undifferentiated or embryonic cells, rather than the tissue of origin.
Genetic instability - under normal conditions, cells are protected from genetic errors because of the many cellular mechanisms in place to prevent them. The dysregulated nature of cancer leads to a high frequency of genetic errors and therefore genetic instability -.
Growth factor independence - cancer cells can proliferate deven in the absence of growth factors
Cell density-dependent inhibition - the cessation of growth after cells reach a certain density is lost in cancer cells.
Cell cohesiveness and adhesion - cells do not stick together which permits surface cells of the tumor to shed into the surrounding body fluids or secretions.
Anchorage dependence - cancer cells can remain viable and multiply without being anchored to neighboring cells or the underlying extracellular matrix.
Cell to cell communication - diminished in cancer cells which interferes with intercellular connections and the responsiveness to membrane-derived signals.
Unlimited lifespan - Cancer cells can divide an infinite number of times. Telomeres, the protective ‘end caps’ on chromosomes, typically shorten with each cell division. Most cancer cells keep high levels of telomerase - an enzyme that prevents telomere shortening. Older and more error prone cells continue to replicate giving rise to cell populations of increasing levels of dysfunction.
Antigen expression - cancer cells contain several antigens that are immunologically different from its normal tissue counterpart (useful as identification markers)
Production of enzymes, hormones, etc - unlike tissues of origin. Can secrete hormones or enzymes that promote metastasis.
Cytoskeletal changes or abnormalities - abnormal intermediate filament types or changes in actin filaments and microtubules to enhance their ability for invasion and meatstasis.
Explain the TNM system
The TNM system is an advancement of the Staging system to determine the spread of cancer in a patient. It looks at the stages of advancement in the tumors, lymph notes, and metastasis in a patient. It looks to describe if tumors have spread, if the cancer is in more than one lymph node, and the degree of metastasis. It’s a more specific and holisitc staging system. It does use a slightly different numbering system than the normal stages of I through IV. For example, tumors (T) can be rated at Tx, T0, T1, T2, etc.
When would surgery be appropriate in the treatment of cancer?
Surgery is often the first treatment for solid tumors. If the tumor is small with well-defined margins, it can be removed completely. It is also used for oncologic emergencies and prophylactic surgery in high risk patients.
Most chemotherapeutic drugs cause pancytopenia due to bone marrow suppression. What are the 3 possible adverse outcomes of this?
Neutropenia- risk for infections
Anemia- causing fatigue
Thrombocytopenia- risk for bleeding
How do cancer cells achieve immortality?
Cancer cells keep high levels of telomerase, an enzyme that prevents telomere shortening. This gives the ability of the chromosomes to continue to replicate forever.
What is a tumor suppressor gene? Give one example.
A tumor suppressor gene encodes proteins to slow the growth of cells and trigger apoptosis when necessary. When the tumor suppressor gene is suppressed as a result of neoplasia, it can allow cancerous cells to proliferate at a faster rate. BRCA1 or 2, TP53
A 40-year-old woman has experienced heavy menstrual bleeding. She was told she has a uterine tumor called a leiomyoma. She is worried she has cancer. What do you tell her? Explain at least 2 differences between a benign and malignant tumor.
Leiomyoma is a benign tumor. (Leiomyosarcoma is malignant) Student can add any of the following: Benign tumors are well-differentiated cells, resemble the cells of tissues of origin, and have a slow, progressive rate of growth. They grow by expansion and remain localized to their site of origin, not capable of metastasizing. They develop a rim of connective tissue around the tumor called a fibrous capsule, which aids in surgical removal. Benign tumors are less of a threat unless they interfere with vital functions
Malignant neoplasms invade and destroy tissue. They grow rapidly, spread to other parts of the body, and lack well-defined margins. They can compress blood vessels and outgrow their blood supply, causing ischemia and tissue injury. Surgery can be more difficult if it has spread.
A 50-year-old woman was diagnosed with breast cancer from tissue biopsy following her diagnostic mammography. They are determining if it has spread to the lymph nodes. (1) Explain what the sentinel node is. (2) How will they determine if it has spread to the lymph system? (3) Would a detailed family history of disease be important to obtain?
The sentinel node is the first lymph node to which the primary tumor drains. The extent of disease may be determined through lymphatic mapping and sentinel lymph node biopsy. A radioactive tracer and/or blue dye is injected into the tumor to determine the first lymph node. This lymph node is examined for the presence of cancer cells. Yes, heredity can be a strong risk factor for cancer in some families.
What is innate immunity
Innate (natural) immunity is the first line of defense in the body’s immune system. There are physical barriers that are part of the innate immunity to prevent foreign microorganisms to enter the body - this can include skin which has closely packed cells in multiple layers as well as a layer of Keratin that creates a salty, acidic environment inhospitable to microbes. The skin also has antimicrobial proteins and lysozymes that inhibit microorganisms and help to destroy them. Additionally the epithelial cells that line and protect the GI, respiratory, and urogenital tract.
In addition to they physical, innate immunity includes cellular defenses in the forms of neutrophils, macrophages, dendritic cells, natural killer cells, and intraepithelial lymphocytes - and they respond to foreign particles.
How does the skin act as a physical barrier?
The skin’s design makes it a strong physical barrier. It has closely packed cells in multiple layers that are continuously being shed. Keratin covers the skin, which creates a salty, acidic environment inhospitable to microbes. It also contains antimicrobial proteins and lysozymes that inhibit microorganisms and help to destroy them.
What cells are involved in innate immunity?
They are divided into two categories: granulocytes (contain granules - neutrophils, eosinophils, and basophils) and agranulocytes (do not contain granules - monocytes, macrophages, lymphocytes).
Neutrophils (most abundant in the body, 55% of white blood cells) are early responders in innate immunity and use phagocytosis to kill microbes.
Eosinophils (1-4%) are active in parasitic infections and allergic responses.
Basophils (<1%) release histamine and proteolytic enzymes.
Monocytes (3-7%) are the largest in size of the leukocytes. They are released from bone marrow and mature into macrophages and dendritic cells where they engage in the inflammatory response and phagocytize foreign substances and cellular debris.
Macrophages have a longer life span, reside in the tissues, and are the first phagocyte that organisms encounter. Neutrophils and macrophages work together on behalf of the host’s initial defense system.
Natural Killer Cells and Intraepithelial cells are both involved in the innate immune response. Natural killer cells can spontaneously kill target organisms, some types of tumors and infected cells without previous exposure to surface antigens. They can also limit the spread of infection and assist in the development of adaptive immune responses through cytokine production. NK cells help with dendritic cell maturation and innate immune control of viral infections.
Dendritic cells are immature cells in lymphoid tissue where they capture foreign agents and transport them to peripheral lymphoid organs. Once they are activated, they mature and migrate to regional lymph nodes. They are key antigen-presenting cells capable of initiating adaptive immunity.
Describe each type of leukocyte and explain their function:
Neutrophils are the most abundant in the body and are an early responder in innate immunity and use phagocytosis to kill microbes. Eosinophils are active in parasitic infections and allergic responses. Basophils release histamine and proteolytic enzymes. Monocytes are the largest in size and are released from the bone marrow and mature into macrophages and dendritic cells where they engage in the inflammatory response and phagocytize foreign substances and cellular debris. Macrophages have a long life span, reside in the tissues, and are the first phagocyte that organisms encounter. Neutrophils and macrophages work together on behalf of the host’s initial defense system.
Describe adaptive immunity:
Adaptive immunity, also called acquired immunity, is the second line of defense and includes both humoral and cellular mechanisms that respond to cell-specific substances known as antigens. Adaptive immunity is acquired through previous exposure to infections and other foreign agents. It can not only distinguish self from nonself but can recognize and destroy specific foreign agents based on their different antigenic properties. This response takes more time but is extremely effective.
What are antigens?
Antigens are foreign substances that elicit an adaptive immune response in the body. Adaptive immunity serves to distinguish self from nonself and to destroy specific foreign agents based on their different antigenic properties.
What are the primary cells of adaptive immunity?
The primary cells of the adaptive immune system are the lymphocytes, APCs (antigen presenting cells), and effector cells.
Describe B & T lymphocytes and discuss their role in immunity:
B lymphocytes produce the antibodies (humoral immunity) and T lymphocytes provide the cell-mediated immunity. B and T lymphocytes have the unique function as the only cells to recognize specific antigens present on the surface of pathogens and to remember them in the future.
What are the differences between innate and adaptive immunity (table 3.1)
Innate - immediate response; general patterns on microbe recognition; similar with each exposure; defense is the epithelium (skin, mucous membranes), phagocytes, inflammation, fever; includes phagocytes (monocytes/macrophages, neutrophils), NK cells, DCs; molecular components include cytokines, complement proteins, acute-phase proteins, soluble mediators.
Adaptive - dependent on exposure; large diversity and specific for each unique antigen; immunologic memory and more rapid and efficient with subsequent exposure; defenses include cell killing via tagging of antigen by antibody for removal; cellular components include T & B lymphocytes, macrophages, DCs, NK cells; molecular components include antibodies, cytokines, complement system.
What is the function of cellular immunity?
T lymphocytes make up the cellular immunity and function to activate other T and B cells, control intracellular viral infections, reject foreign tissue grafts, activate autoimmune processes, and activate delayed hypersensitivity reactions.
Cellular immunity involves activation of specific T-lymphocytes which defend the body against intracellular microbes, like viruses.
CD4+ Helper T Cells are activated and secrete cytokines, these activate many inflammatory cells (macrophages, basophils, neutrophils) which further propagates processes for pathogen destruction.
What are the 5 classes of immunoglobulins
IgG - 75%; antiviral, antibacterial, antitoxin. Crosses placenta to give immunity to fetus.
IgA - saliva, tears, colostrum, bronchial, GI, prostatic, and vaginal secretions. Local immunity on mucosal surfaces. Prevents attachment of viruses and bacteria onto epithelial cells.
IgM - lysis of microorganisms. 1st antibody produced by the fetus and immature B lymphocytes and first Ig to be produced in response to an infection. Monitoring IgM levels is helpful clinically, as increased levels indicate an active infection.
IgD - low levels; unknown functions.
IgE - least common, responsible in inflammation and allergic reactions as well as combating parasitic infections.
Describe the differences between active and passive immunity?
Active immunity is acquired from an immune response either via vaccination or from environmental exposure. Active immunity is long lasting but takes days to weeks after the first exposure to fully develop a response.
Passive immunity is immunity transferred from another source. The most common example is from mother to fetus, where the IgG antibodies are passed on either via the placenta or breast milk or colostrum. Passive immunity is short-term protection lasting only weeks to months.
What are type I hypersensitivity reactions?
Type I hypersensitivity reactions are IgE mediated reactions that develop quickly upon exposure to an antigen. Allergies fall into this category.
What cells are involved in type I reactions? (Know their roles.)
Mast cells, basophils, and eosinophils.
Mast cells and basophils release histamine, a vasodilator that relaxes vascular smooth muscle, increases permeability of capillaries and venules, and causes smooth muscle contraction and bronchial constriction.
Eosinophils are drawn in by cytokines to the site of allergen exposure
What are type II hypersensitivity reactions?
Type II hypersensitivity reactions (cytotoxic) are antibody-mediated reactions where IgG or IgM antibodies are directed against target antigens on specific host cell surfaces or tissues. The antigens may be intrinsic or extrinsic. Type II reactions occur in 4 ways:
1) Complement activated cell destruction: lysis of the cell and activation of macrophages, which then further destroys the target cells by phagocytosis.
2) Antibody dependent cell cytotoxicity: components of the innate and adaptive immune responses destroy target cells. Antibody binding on the target cell surface causes the release of chemotactic substances and teh destruction of the target cell.
4) Complement and antibody mediated inflammation - can occur rather than phagocytosis or cell lysis, when antibodies are deposited on extracellular tissue components. The activated leukocytes release injurious substances that cause inflammation and tissue damage.
5) Antibody mediated cellular dysfunction - antibody binding to specific target cell receptors does not lead to death, but rather to unwanted changes in cell function.
What are autoimmune disorders?
Autoimmune diseases occur when the body’s immune system fails to differentiate self-antigens from nonself antigens and mounts an immunologic response against host tissues.
What are the different types of type I hypersensitivity reactions (allergic rhinitis, anaphylaxis) and what are their appropriate treatments
Type I hypersensitivity reactions are IgE-mediated reactions that develop quickly upon exposure to an antigen. As this is the classic allergic response, the antigens are known as allergens. Common allergens include pollen proteins, foods, house dust mites, animal dander, household chemicals, and even pharmaceutical agents, like penicillin. Exposure can be through inhalation, ingestion, injection, or skin contact and can cause a localized or systemic reaction. Type I reactions include seasonal rhinitis, asthma, and in severe cases, anaphylaxis.
Antihistamines and intranasal corticosteroids. Allegra, Zyrtec, Benadryl. Flonase, Nasacort. Epipen.
What is autoreactivity?
If a self reactive cell is not eliminated, it can recognize the body’s own tissues and create an immune response against the self antigen. It results in the destruction of cells and tissues in the immune system.
What is anergy?
When the loss of lymphocyte response to an antigen occurs and causes a lack of cellular and/or humoral immunologic response, this is called anergy. Anergy is the state of immunologic tolerance to specific antigens.
What are autoantibodies?
Autoantibodies are produced when the immune system loses its ability to recognize self, and they act against the host’s tissues.
What are positive and negative selection?
Positive selection takes place in the thymus during maturation when T cells encounter self-peptides bound to MHC molecules. The T cells taht display no reactivity to the host’s MHC antigens are allowed to mature (positive selection).
The T cells that have a high affinity to self antigens are sorted out and undergo apoptosis (negative selection),
What are the 2 general causes of autoimmune diseases?
Genetic and environmental factors. There are susceptibility genes that combine with a trigger event.
How do you diagnose an autoimmune disease?
Diagnosis is made by history, physical, and serological findings. The following criteria must be met: evidence of an autoimmune reaction, the immunologic findings are not secondary to another condition, and no other identifiable causes are found.
What is Graves’ disease?
Graves disease is an autoimmune disorder characterized by abnormal stimulation of the thyroid gland by thyroid stimulating hormone receptor antibodies that act through the normal receptors. It is a state of hyperthyroidism, goiter, and ophthalmopathy.
What is SLE?
SLE is systemic lupus erythematosus, a chronic inflammatory disease that can affect almost any organ system. It is characterized by the presence of autoantibodies and non-self antigens.
What is HIV?
HIV is a retrovirus that selectively attacks the CD4+ T lymphocytes, the immune cells responsible for coordinating the immune response to infection. Because of this, people with HIV infection are more susceptible to severe infections with ordinarily harmless organisms.
How is HIV spread?
HIV is transmitted from one person to another through sexual contact, blood-to-blood contact, or from mother to child during pregnancy, birth, or breastfeeding. HIV is not spread via saliva or causal contact.
What is seroconversion?
Seroconversion is the term when an infected person’s blood converts from being negative for HIV antibodies to being positive.
What is the window period?
The window period is the time from infection to seroconversion, usually 1-3 months.
What is the latent and last phase of HIV infection?
The latent phase is characterized by no signs or symptoms of illness. The last phase, or AIDS illness, occurs when the CD4+ cell count falls to less than 200 cells/µL or exhibits an AIDS-defining illness.
What are opportunistic infections?
Opportunistic infections are those common organisms that do not produce infection without impaired immune function.
Describe the different diagnostic methods for HIV.
The best diagnostic method to detect HIV is the HIV antibody test, known as the enzyme immunoassay (EIA), or ELISA. If positive, it is followed by the confirmatory test, the Western blot assay. The EIA detects antibodies produced in response to HIV infection. The polymerase chain reaction (PCR) test is a nucleic acid test that can detect HIV DNA. It tests for the presence of the virus, rather than the antibody, which is helpful in diagnosing HIV infection in infants born to infected mothers. These infants would have their mother’s antibodies whether or not they have been infected.
What are the signs and symptoms of acute (primary phase) HIV infection (chart 3.3
Fever, fatigue, rash, headache, lymphadenopathy, pharyngitis, athralgia, myalgia, night sweats, GI problems, aseptic meningitis, oral or genital ulcers
What are the 2 phases of acute inflammation?
Acute inflammation can be divided into the vascular stage and the cellular stage. The vascular phase begins with temporary vasoconstriction, followed by vasodilation as a result of histamine and nitric oxide. Heat and redness appear. This leads to increased vascular permeability and exudate moves into the extravascular space, which causes an interstitial osmotic pressure increase so an increase in fluid. This leads to swelling, pain, and impaired function. As fluid movement slows, blood clotting occurs due to increased red cells, leukocytes, platelets, and clotting facto, and it helps to contain the spread of infectious microorganisms.
The cellular stage delivers leukocytes, predominantly neutrophils, to the site of injury to initiate their immune response.
What are the steps in the cellular phase?
Adhesion and margination, transmigration, and chemotaxes
Describe the process of chronic inflammation and discuss how it often develops.
Chronic inflammation may result from recurrent or progressive acute inflammatory processes. It involves macrophages and lymphocytes instead of neutrophils.
Nonspecific chronic inflammation includes an accumulation of macrophages and lymphocytes at the site of injury - they accumulate due to ongoing chemotaxis and this leads to fibroblast proliferation and scar formation.
Granulomatous lesion consists of macrophages encompassed by lymphocytes and is often associated with foreign bodies such as splinters, asbestos, sutures, and silica.
What are the 3 stages of wound repair?
There are three general stages of wound healing: (1) the inflammatory phase, (2) the proliferative phase, and (3) the wound contraction and remodeling phase.
What factors can inhibit wound repair?
Factors that affect wound healing negatively include malnutrition, decreased blood flow and oxygen delivery, impaired inflammatory and immune responses, infection, wound separation, foreign bodies, and age.
Explain the challenges of diagnosing autoimmune disorders.
There are over 80 identified, many with overlapping presentations. Many manifestations are nonspecific and are seen in other non-autoimmune diseases. Blood testing isn’t perfect either, as some tests are more generic and can be elevated in the presence of other diseases.
Explain the challenges of diagnosing autoimmune disorders.
There are over 80 identified, many with overlapping presentations. Many manifestations are nonspecific and are seen in other non-autoimmune diseases. Blood testing isn’t perfect either, as some tests are more generic and can be elevated in the presence of other diseases.
What allows the lymphocyte to differentiate between self and foreign moelcules
Major histocompatibility complex (MHC) molecule
Which immunoglobulin passes immune factors from the mother to the fetus
IgG
A 12-year-old female presents with itchy eyes, nasal congestion and drainage, and sneezing every spring when the pollen count is high. (1) Explain the immunologic mechanisms that are responsible for her symptoms. (2) What type(s) of treatment might be used to relieve her symptoms?
The 12 year old is experiencing a type I hypersensitivity. When allergens like pollen are detected in the body, IgE is activated and triggers an immunoresponse, including the release of histamine in the body. This is because pollen, and other allergens, are antigens and known to the body as “non-self.”
Two treatments that could help relieve her sypmtoms include an antihistamine and/or corticosteroid. A second generation drug such as Claritin or Zyrect, combined with a nasal spray like Flonase should help relieve her symptoms.
(1) Mast cells, basophils, and eosinophils play an important role in the development of type I reactions because they contain the chemical mediator histamine. A primary or initial-phase response is vasodilation, vascular leakage, and smooth muscle contraction. A secondary or late-phase response is characterized by more intense infiltration of tissues with eosinophils and other acute and chronic inflammatory cells, as well as tissue damage. (2) Antihistamines and intranasal corticosteroids are the mainstay of treatment.
Can an antibiotic alone heal an abscess?
Antibiotics are unable to breakthrough the protective layer of fibers formed around the abscess. In order to heal the abscess it must be lanced and drained.
An appendectomy is performed on a 16-year-old boy who is hospitalized for right lower quadrant abdominal pain of 18 hours’ duration. The surgical specimen is edematous and erythematous. An infiltrate of which cells would be most characteristic of the process occurring here?
Neutrophils
Which hypersensitivity reactions can be treated with the administration of epinephrine?
Type I
A 32-year-old woman presents to the clinic for her initial obstetrics visit, about 10 weeks into her pregnancy. She is in a monogamous relationship. (1) Should an HIV test be part of her initial blood work? Why?
Yes. Transmission from mother to infant is the most common way that children become infected. The CDC recommends all people between ages 13 and 64 be routinely screened for HIV. Earlier detection and treatment lead to better outcomes.
An infant is born, and its initial antibody test is positive for HIV. (2) Does this mean the infant is infected? What would be the more appropriate test to detect HIV in this infant?
No. The polymerase chain reaction (PCR) test is a nucleic acid test that can detect HIV DNA. It tests for the presence of the virus, rather than the antibody, which is helpful in diagnosing HIV infection in infants born to infected mothers. These infants would have their mother’s antibodies whether or not they have been infected.
The cells primarily responsible for the tissue building that occurs during the proliferative phase of wound healing are known as what?
Fibroblasts
What cell mediator is the primary cause of vasodilation seen in acute inflammation?
Histamine
Which lab value will typically be increased in a viral infection?
Lymphocytes
Which lab value will typically be increased in a viral infection?
Lymphocytes
What is the function of blood?
The function of blood is to transport gases, nutrients, wastes, and hormones. It helps to regulate temperature, pH, and fluid volume.
What are the three stages of hemostasis?
Hemostasis is divided into vascular constriction, formation of the platelet plug, and blood coagulation in order to stop the flow of blood.
What is vitamin K needed to synthesize?
Vitamin K is needed to synthesize protein coagulation factors II, IX, and X, prothrombin, and protein C. A deficiency of vitamin K or liver failure will result in abnormal bleeding as prothrombin will not be made.
Discuss the intrinsic and extrinsic pathways:
The intrinsic and extrinsic pathways both form prothrombin activator. The intrinsic pathway begins with activation of factor XII and can cause clotting in 1 to 6 minutes, considered the slower process. The extrinsic pathway can cause clotting in 15 seconds and begins with the release of tissue thromboplastin from the subendothelial cells. Both pathways converge to activate factor X, the conversion of prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin, the material needed to stabilize a clot. Both methods are needed for successful hemostasis.
What are the natural and drug therapy anticoagulants?
The natural anticoagulants found in the body are antithrombin III, protein C, and protein S. The drug therapy anticoagulants are Warfarin (inhibits coagulation factors dependent on vitamin K for synthesis), Heparain (stops the formation of fibrin), Dabigatran (oral anticoagulant).
What is peripheral vascular resistance?
Peripheral vascular resistance is the collective resistance of all the vessels in the peripheral circulation. Resistance is the opposition to flow caused by friction between the moving blood and the stationary vessel wall.
Hemodynamics or blood flow is affected by what factors?
Hemodynamics are affected by blood pressure, vessel resistance, and blood flow. Resistance is described above. Blood flow is affected by the blood vessel radius and blood viscosity.
What is cardiac output?
Cardiac output is the volume of blood the heart pumps per minute. It can be calculated by multiplying the heart rate by the stroke volume, which is the blood pumped out by the ventricle with each beat. CO = SV x HR.
What is preload?
Preload is the end-diastolic pressure when the ventricle has been filled and represents the volume work of the heart. It’s called preload because it is the work on the heart before the contraction begins. It is mainly the result of venous return of blood to the heart and the stretch of the cardiac muscle fibers. In short, it is the volume of blood in the ventricles the heart has to eject.
What is afterload?
Afterload is the pressure the heart exerts to overcome the pressure in the heart vessels to be able to eject the blood from the heart.
What is cardiac contractility?
Cardiac contractility is the ability of the heart to change its force of contraction without changing its resting (diastolic) length. This is strongly influenced by the number of calcium ions available to participate int he contractile process. Contractility increases cardiac output independent of preload or afterload.
What is an inotrope?
An inotrope is an effect that increases or decreases the contractile force. Positive inotropic effects (increasing contractile force) include the sympathetic nervous system, afterload, catecholamines, heart rate, drugs, intracellular calcium levels. Negative inotropic effects (decrease contractile force) include the parasympathetic nervous system, heart failure, hypoxia, and drugs.
What is mean arterial pressure?
Mean arterial pressure is the average pressure in the arterial pressure in the arterial system during a cardiac cycle and is a good indicator of tissue perfusion. The mean arterial pressure is the product of the cardiac output (SVHR) and the peripheral vascular resistance (MPA = COPVR)
Understand the renin-angiotensin-aldosterone system
In the RAAS, kidneys secrete renin, which gets converted eventually into angiotensin II, that forms ADH and aldosterone to reabsorb sodium and water. It increases fluid retention and vasoconstriction. This worsens both pre and afterload. RAAS plays a vital role in blood pressure regulation. If there are changes in extracellular fluid, extracellular sodium levels, a drop in blood pressure, or increased sympathetic activity, the kidney will release renin. In the bloodstream, renin converts angiotensinogen into angiotensin I. Angiotensin I is converted to angiotensin II in the lungs by ACE (angiotensin-converting enzyme). Angiotensin II is a vasoconstrictor, mainly of the arterioles. Arteriole constriction will increase the PVR, regulating blood pressure for a short period of time. Aldosterone will increase salt and water retention by the kidney contributing to the long-term regulation of blood pressure.
Be familiar with hypercoagulability states
Hypercoagulability is the accelerated activity of the clotting system. There are conditions that create increased platelet activity and conditions that cause increased activity of the coagulation pathways. Arterial thrombi are often a result of conditions characterized by an increase in platelet numbers or restricted blood flow with platelet adhesion. Venous thrombi are associated with conditions, genetic in nature or acquired, that decrease the amount of anticoagulation factors or produce a stasis of blood, which in turn increases the number of pro-coagulation factors.
What is thrombocytosis?
Thrombocytosis is defined as a platelet count greater than 450,000/microL. The overall platelet count is regulated by a negative feedback loop. If the platelet count falls below normal limits, hormonal thrombopoietin levels will rise to increase the number of platelets, and when the count reaches normal limits, thrombopoietin levels will decrease. Primary thrombocytosis is due to a disorder of the hematopoietic stem cells within the bone marrow resulting in abnormally high levels of thrombopoietin, which leads to an overproduction of platelets. Secondary thrombocytosis is is also an abnormal thrombopoietin production which overproduces platelet production, but is due to a disease state (tissue damage from surgery, infection, cancer, and chronic inflammatory conditions).
What are the most common causes of inherited disorders of hypercoagulability?
Inherited disorders of hypercoagulability are most commonly caused by a mutation of the factor V gene or prothrombin gene. The mutant factor V cannot be inactivated by protein C which helps to regulate anticoagulation. As a result, a factor V mutation will lead to an increased risk fro developing deep vein thrombosis.
What are acquired or secondary factors of hypercoagulability that lead to venous stasis?
Secondary hypercoagulability that leads to venous stasis can be caused by bed rest, use of oral contraceptives, smoking, pregnancy and postpartum, sepsis, heart failure, cancer.
What is thrombocytopenia?
Thrombocytopenia is a reduction in platelets which increase a risk of bleeding.
Be familiar with hemophilia A and DIC pathology, clinical presentation, diagnosis, and treatment.
Hemophilia A is a recessive genetic disorder that causes an insufficient production in factor VIII which promotes clotting and adhesion of platelets to the vessel wall, bleeding in the soft tissues, GI tract, and joints. Trauma prevention is very important, Factor VIII replacement therapy is the current treatment. Disseminated intravascular coagulation (DIC) is characterized by widespread coagulation and bleeding. DIC begins with the activation of the extrinsic or intrinsic coagulation cascade, the result of unregulated generation of thrombin, resulting in systemic formation of fibrin. All the major anticoagulant levels are decreased. Microthrombi are formed causing vessel occlusion and tissue ischemia. As all availability coagulation proteins and platelets are being used to form clots, severe hemorrhage ensues. Treatment is focused on managing the primary disease, replacing clotting components, and preventing further activation of clotting mechanisms.
Be familiar with hemophilia A and DIC pathology, clinical presentation, diagnosis, and treatment.
Hemophilia A is a recessive genetic disorder that causes an insufficient production in factor VIII which promotes clotting and adhesion of platelets to the vessel wall, bleeding in the soft tissues, GI tract, and joints. Trauma prevention is very important, Factor VIII replacement therapy is the current treatment. Disseminated intravascular coagulation (DIC) is characterized by widespread coagulation and bleeding. DIC begins with the activation of the extrinsic or intrinsic coagulation cascade, the result of unregulated generation of thrombin, resulting in systemic formation of fibrin. All the major anticoagulant levels are decreased. Microthrombi are formed causing vessel occlusion and tissue ischemia. As all availability coagulation proteins and platelets are being used to form clots, severe hemorrhage ensues. Treatment is focused on managing the primary disease, replacing clotting components, and preventing further activation of clotting mechanisms.
How can anemias be classified according to size and color?
Anemia can be characterized as normochromic (normal color) or hypochromic (decreased color). Red cells can be classified as normocytic (normal size), microcytic (small cells), and macrocytic (large cells).
Be familiar with sickle cell disease, thalassemia, iron deficiency anemia, vitamin B12 and folate deficiency anemia – pathology, clinical presentation, diagnosis, and treatment.
Sickle cell disease is a genetic disorder characterized by chronic hemolytic anemia, pain, and organ failure caused by abnormal hemoglobin S. Sickle cell disease is a single mutation in the hemoglobin molecule. In conditions of decreased oxygen levels, the cell becomes sickled as the abnormal hemoglobin sticks together. With proper oxygenation, the cells may return to normal shape; with, the cell will remain permanently sickled. This may lead to hemolysis or occlusion. Clinical presentation can include leg ulcers, damage to many organs, acute chest syndrome, asplenia. Diagnosis is confirmed by screening at birth, hemoglobin electrophoresis. Treatment is focused on preventing sickling episodes like infections, cold exposure, severe physical exertion, acidosis, and dehydration.
Iron Deficiency Anemia is the loss of iron through bleeding or increased demands. Iron is a component of heme and decreased levels lead to impaired oxygen delivery. Clinical presentation includes fatigue, dyspnea, angina, and tachycardia, pica. IDA presents with low hemoglobin and hematocrit, decreased iron stores, low serum iron and ferritin levels. Prevention is key - eating a diet rich in iron containing foods, taking iron fortified vitamins, and treating any underlying chronic blood loss.
Thalassemia is a genetic disease with defective hemoglobin synthesis and hemolysis. It is a hypochromic, microcytic anemia due to decreased synthesis of the affected chain coupled with continued production and accumulation of the unaffected globin chain. People with Thalassemia major must undergo blood transfusions in life or risk severe growth retardation. The ineffective hematopoiesis and hemolysis leads to increased erythropoietin secretion and hyperplasia in the bone marrow which impairs bone growth and leads to osteoporosis or osteopenia.
Vitamin B12 Deficiency Anemia is caused by impaired DNA synthesis that results in enlarged red blood cells. B12 is necessary for DNA synthesis and development of the cel nuclei. The clinical presentation includes moderate to severe anemia and mild jaundice. The the MCV is elevated due to large cells and the MCHC is normal. There can be neurologic changes as well caused by meylin breakdown. Diagnosed by low B12 serum level. Treatment includes lifelong intramuscular injections or high oral doses.
Folic Acid Deficiency is similar to B12 deficiency, as it is required for DNA synthesis and red blood cell maturation. Most common causes are malnutrition. Supplementation should support people with this condition.
What is neutropenia and what are people who have it at risk for?
Neutropenia is the abnormal decrease in the circulating neutrophils, thus weakening the immune system. It is the result of decreased production, increased destruction, or relocation to tissue from the bloodstream. For some it is congenital, for others it can be caused by lupus, rheumatoid arthritis, HIV, and hematologic cancers.
What are the five types of lipoproteins? Which one is the good and bad cholesterol?
High Density Lipoprotein is the good cholesterol. Low density lipoprotein is the bad cholesterol. There is also very low density lipoprotein, intermediate density lipoprotein, and chylomicrons.
Where does lipoprotein synthesis take place?
Lipoprotein synthesis takes place in the liver and the small intestine.
What are xanthomas?
Xanthomas are cholesterol deposits that will develop along the tendons with hypercholesterolemia. This can lead to atherosclerosis.
Be familiar with hyperlipidemia pathology, clinical presentation, diagnosis, and treatment.
Hyperlipidemia is the the excess of lipids in the blood. Nutrition, genetics, medications, comorbid conditions, and metabolic disease can all raise blood lipid levels. Treatment focuses on dietary and therapeutic lifestyle changes like increasing physical activity, weight reduction, and smoking cessation. If those don’t work, hyperlipidemia drugs can work.
What is atherosclerosis and what is it a major risk factor of?
Atherosclerosis is the hardening of the arteries and it is a major risk for ischemic heart disease, stroke, and peripheral vascular disease. Hyperlipidemia.
Be familiar with atherosclerosis pathology and clinical presentation.
The etiology is the “response to injury theory” in which injury of a blood vessel (due to inflammation, immune mechanisms, high cholesterol, hypertension, smoking) results in macrophages scavenging the excess cholesterol. They oxidize the LDL and become foam cells which decrease cholesterol from circulation but will release factors that will injure the endothelial cells and the blood vessel. Foam cells will keep collecting and form a lesion on the blood vessel wall, the macrophages will secrete growth factors that secrete cell proliferation. The macrophages will die and leave behind their necrotic debris and then we start to accumulate lipids and this will generate our plaque. The lesion will be covered by smooth muscle, extracellular matrix, and will inhibit flow and increase blood pressure and resistance. If the lesion ruptures, it can cause hemorrhage or a thrombosis. This can present as angina, impotence, wounds that wont heal.
What causes coronary artery disease (CAD)?
Coronary artery disease (CAD) is impaired coronary blood flow that causes heart disease. CAD leads to myocardial ischemia and angina, myocardial infarction (heart attack), cardiac arrhythmias, abnormalities in conduction, heart failure, and even death.
What are the major risk factors of CAD?
The major risk factors of CAD are smoking, chronic high blood pressure, increased LDL, decreased HDL, diabetes, age, abdominal obesity, and decreased physical activity.
Be familiar with the methods used to assess coronary blood flow and myocardial perfusion (electrocardiography, exercise stress testing, echocardiography, Doppler ultrasonographic imaging, cardiac MRI and CT, and cardiac catherization and angiography).
Electrocardiography - records electrical potential differences during the cardiac cycle. It is most frequently used cardiovascular procedure that can diagnose and identify ventricular conduction defects, arrhythmias, electrolyte imbalances, drug effects, and genetically mediated electrical or structural abnormalities.
Exercise stress test - observes cardiac function under stress (running on a treadmill). Used for adults with suspected ischemic heart disease, but also physiologic response preoperatively, post MI or revascularization, or the severity of arrhythmias.
Echocardiography - best method to check for structure and function of the heart.
Doppler Ultrasonographic imaging
Cardiac MRI and CT
Cardiac Catheterization - a catheter is inserted into the great vessels and chambers of the heart to inject radiographic contrast.
Angiography
Be familiar with the disease states in acute coronary syndrome.
Acute coronary syndrome (ACS) represents a range of acute ischemic heart diseases ranging from unstable angina to myocardial infarction. It results from disruption of an atherosclerotic plaque.
What are the 2 different ways heart failure can be defined?
Heart failure can be described in terms of systolic dysfunction (the ejection of blood during systole is impaired) or diastolic dysfunction (impaired filling capability of the heart during diastole).
Be familiar with heart failure pathology, clinical presentation, diagnosis, and treatment.
Clinical manifestations of heart failure include shortness of breath, fatigue, weakness, fluid retention. Diagnosis depends on history, physical exam, lab studies, electrocardiography, etc. Treatment is aimed at stabilizing and correcting the cause of the cardiac dysfunction to receive symptoms, improve quality of life, and reduce risk factors. Diuretics, ACE inhibitors or angiotensin II receptor blockers, beta blockers, digoxin, and vasodilators can be used.
Be familiar with the different types of cardiomyopathies.
Cardiomyopathy is a disease of the heart muscle that causes it to be enlarged, thick, or rigid. Hypertrophic cardiomyopathy is the thickening of the heart wall, especially in the left ventricle. It makes the chamber smaller which causes an abnormal ventricular filling and decreased stroke volume. Dilated cardiomyopathy causes the left ventricle to be enlarged and cannot contract properly to conduct the blood. Restrictive myopathy causes the heart to lose elasticity so it does not expand well to fill with blood.
Be familiar with the different types of arrhythmias
Cardiac arrhythmias are electrical impulses in the cardiac conduction system that fail to coordinate causing the heart rate to increase, decrease, or have an irregular rhythm. There are Tachyarrhythmias in which the heart rate is above 100 beats/min which decreases the fill time of the heart and decreases the CO. Bradyarrhthmias slow the heart rate to less than 60 beats/min and can decrease profusion of our organs.
What are the current stages of hypertension?
Currently, normal blood pressure is defined as less than 120/80. Elevated blood pressure is < 130/80; hypertension stage 1 is < 140/90; and hypertension stage 2 is > 140/90.
Be familiar with hypertension pathology, clinical presentation, diagnosis, and treatment.
There are both non-modifiable risk factors (age, family history, gender, race) and modifiable (salt, excessive calorie, alcohol intake). Hypertension can promote and accelerate plaque formation and rupture, it is also a risk factor for CAD, peripheral artery disease, stroke, and heart failure. Prolonged elevation of blood pressure places an increased workload on the left ventricle as it increases the pressure the heart must pump against as it ejects blood into the systemic circulation. Over time, the left ventricle hypertrophies as it compensates for the increased pressure. Left ventricular hypertrophy is a major risk factor for heart disease and even death. Hypertension is diagnosed with repeated blood pressure measurement. Treatment is usually lifestyle changes as well as medication like diuretics, ACE inhibitors, calcium channel receptor blockers.
What is cardiogenic shock?
Cardiogenic Shock is occurs when the heart fails to pump blood sufficiently to meet the body’s needs.
What causes cardiogenic shock?
The most common cause is extensive damage to the left ventricle from a myocardial infarction where there is decreased stroke volume and cardiac output which causes low oxygen and perfusion.
Myocardial infarction, myocardial contusion, sustained arrhythmias, or cardiac surgery
What is the most specific test for diagnosing iron deficiency anemia
Ferritin
What can increase the change of clotting?
Protein C deficiency
What are two natural anticoagulants
Proteins C and S
Hemolytic anemias are characterized by
premature destruction of red blood cells, decrease in erythropoiesis, and sickle cell disease and thalassemias are included.
Three ways to treat or prevent a sickling crisis in sickle cell disease:
hydroxyurea, immunizations, treating infections
The spleen of a patient with sickle cell anemia would be expected to be:
shrunken
What do fatty streaks of atherosclerotic lesions consist of?
Macrophages and smooth muscle cells
What is the description and use of the various cardiac procedures: cardiac catheterization, exercise stress testing, electrocardiography, echocardiography
Cardiac catheterization:
A catheter is inserted into the great vessels and chambers of the heart and it is best to assess need for coronary artery bypass graft and and stenting.
Exercise stress testing:
Observes cardiac function under stress and is best to assess suspected ischemic heart disease.
Electrocardiography:
Records electrical potential differences during the cardiac cycle and is best to assess for arrhythmias and myocardial infarction.
Echocardiography:
Checks for structure and function of the heart and is best to assess ventricular function and heart failure.
What is the description and use of the various cardiac procedures: cardiac catheterization, exercise stress testing, electrocardiography, echocardiography
Cardiac catheterization:
A catheter is inserted into the great vessels and chambers of the heart and it is best to assess need for coronary artery bypass graft and and stenting.
Exercise stress testing:
Observes cardiac function under stress and is best to assess suspected ischemic heart disease.
Electrocardiography:
Records electrical potential differences during the cardiac cycle and is best to assess for arrhythmias and myocardial infarction.
Echocardiography:
Checks for structure and function of the heart and is best to assess ventricular function and heart failure.
Explain the differences in the pathophysiology, symptoms, and whether nitroglycerin and/or rest will relieve symptoms in stable angina, unstable angina, and myocardial infarction.
With atherosclerotic disease, the coronary vessel lumens are narrowed and blood supply to the heart is diminished. With exertion, the vessels cannot adequately vasodilate. This can manifest as chest pain or tightness and/or shortness of breath. Stable angina is experienced as a pain that radiates from the arm up to the neck and chest during moments of exertion. This takes place in atherosclerosis with the narrowing of the blood vessels that doesn’t allow for appropriate cardiac output even though the heart is working to compensate for the narrowed vessels. The result of the lack of needed oxygen and the heart muscle contractions is a build up of lactic acid and results in an acidic state, hence the pain. Nitroglycerin and rest should relieve some of the symptoms.
Stable angina- The heart is stable at rest but cannot keep up with the demand of exertion. Stable angina typically has a >70% stenosis of the coronary arteries. It is relieved by rest or nitroglycerin (vasodilator).
Unstable angina- With increasing occlusion of the coronary vessel(s), the demands of the resting heart may become too great. When the patient experiences angina without exertion, or when the level of exertion necessary to cause anginal symptoms decreases, this is called unstable angina. It can be relieved by nitroglycerin, but not rest. Unstable angina means one or more coronary vessels is nearly totally occluded.
Myocardial infarction- If a plaque ruptures, coronary thrombosis can cause complete occlusion. If collateral flow is inadequate, the tissue supplied becomes ischemic. Without oxygen, a portion of the muscle can die. MI can present as chest pain unrelieved by rest, sometimes radiating down the left ram or into the jaw or neck, dyspnea, nausea/vomiting, sweating, and/or other signs of distress. Other symptoms include a crushing pain or like “something is sitting on my chest.” Women may present with weakness, fatigue, shortness of breath, or GI complaints. Symptoms are not relieved by nitroglycerin.
