[01.01] Introduction to Pathology_ Adaptation and Overview of Cell Injury & Death (Forms of Adaptation, Causes of Cell Injury, Reversible Injury, Necrosis) V2.1

Pathology

What field attempts to explain the whys and wherefores of patient signs and symptoms, providing a rational basis for clinical care and therapy?

Bridge between basic sciences and clinical medicine

How is pathology described in its role connecting foundational scientific knowledge to patient care?

General Pathology

What type of pathology is concerned with the common reactions of cells and tissues to injurious stimuli?

Systemic Pathology

What type of pathology examines alterations and underlying mechanisms in organ-specific diseases, dealing with different body systems?

Understanding general pathology concepts

According to Dr. Koa, what is crucial for students to have a good grasp of in order to understand systemic pathology?

Histology and anatomy

What two fields of understanding are critical in comprehending pathologies, such as identifying a fatty liver?

Etiology

What aspect of the disease process refers to its cause, which can be genetic or acquired?

Pathogenesis

What aspect of the disease process involves the biochemical and molecular mechanisms of its development?

Morphologic changes

What aspect of the disease process describes the structural alterations induced in the cells and organs of the body?

Clinical manifestations

What aspect of the disease process represents the functional consequences of the structural alterations?

Robbins and Cotran Pathologic Basis of Disease, 10th Edition

What is the main reference recommended by Dr. Koa for in-depth explanations of pathologies?

Homeostasis

What is the steady state that a cell maintains when handling physiologic demands?

Adaptations

What refers to reversible functional and structural responses to changes in physiologic states and some pathologic stimuli, allowing cells to survive and function in new, altered steady states?

Recovery to original state

What happens to a cell when stress is eliminated after adaptation, without harmful consequences?

Hypertrophy

What form of adaptation involves an increase in the size of cells and their functional activity?

Hyperplasia

What form of adaptation involves an increase in the number of cells?

Cells that enter the cell cycle

What type of cells can undergo hyperplasia?

Cardiac muscle cells

What is an example of a cell type that does not undergo hyperplasia?

Cardiac hypertrophy

What is the term for injury to cardiac muscle cells that do not undergo hyperplasia?

Atrophy

What form of adaptation involves a decrease in the size and metabolic activity of cells?

Metaplasia

What form of adaptation involves a change in the phenotype of cells?

Dysplasia

What is the fifth type of adaptation referred to by Dr. Koa, which is a form of neoplasia?

Neoplasia

What term, according to the National Cancer Institute, refers to uncontrolled, abnormal growth of cells or tissues in the body, which can be benign or malignant?

Cell Injury

What is the term for the sequence of events that follows when limits of adaptive responses are exceeded, or cells are exposed to injurious agents, stress, essential nutrient deprivation, or compromised by mutations?

Cell Death

What is the end result of progressive or persistent cell injury, which is irreversible?

Reduced blood flow to bodily tissue

What is ischemia defined as?

Embolisms, mechanical compression, atherosclerosis

What are three causes of ischemia?

Myocardial infarction (MI) or heart attack

What may occur in cases of total obstruction due to atherosclerosis?

Necrosis and Apoptosis

What are the two principal pathways of cell death?

Intracellular accumulations

What may be associated with metabolic derangements in cells and sublethal chronic injury, involving proteins, lipids, and carbohydrates?

Pathologic calcification

What is the term for calcium deposition seen at sites of cell injury and cell death?

Atrophy of cells

What characteristic morphological change accompanies aging, causing a decrease in the size of organs?

Increased production of cellular structural components

What is hypertrophy due to, such as structural proteins?

When the cell is able to enter the cell cycle

Under what condition may hypertrophy and hyperplasia coexist and contribute to increased organ size?

Neurons and cardiac muscle cells

What are two examples of permanent cells?

Increased functional demand or stimulation of hormones/growth factors

What causes physiologic hypertrophy?

Skeletal muscles

What type of muscle cells respond to increased metabolic demands by undergoing hypertrophy, often due to increased workload?

Uterus during pregnancy

What organ undergoes physiologic hypertrophy due to hormone-induced enlargement of its smooth muscle fibers?

Myometrium

What is the thickest, middle layer of the uterus composed of smooth muscle cells that undergoes enlargement during pregnancy?

Physiologic hypertrophy

What kind of hypertrophy is seen in a gravid uterus adapting to accommodate a growing fetus?

Increased width of smooth muscle cells

What histologic change is observed in a gravid uterus compared to a normal uterus?

Hypertrophic heart due to chronic hemodynamic overload

What is an example of pathologic hypertrophy, often resulting from hypertension or faulty cardiac valves?

Cardiomegaly, left ventricular hypertrophy

What condition might chronic hypertensive patients exhibit on chest x-rays?

1.5 cm

What is the normal thickness of the left ventricle (LV) free wall?

Aortic stenosis and mitral stenosis

What valvular defects can cause hypertrophic heart?

Concentrically larger

How does LV hypertrophy appear as seen in cross-section?

Increase in the diameter of individual cardiac muscle cells, enlargement of nucleus, box-car nucleus

What are three features of hypertrophy seen in cardiac myocytes?

Heart failure (arrhythmia) or sudden death

What can hypertrophy of the heart eventually lead to when it becomes maladaptive beyond a certain point?

Increased production of cellular constituents, such as proteins

What is the mechanism of hypertrophy?

Mechanical sensors, growth factors, and vasoactive agents

What constitutes the integrated actions in the molecular pathogenesis of cardiac hypertrophy?

PI3K/AKT (phosphoinositide 3-kinase)

What is the signaling pathway for physiologic exercise-induced muscle hypertrophy?

Downstream signaling of G-protein coupled receptors

What is the signaling pathway for pathologic hypertrophy?

Transcription factors

What components are activated by signaling pathways to increase the synthesis of muscle proteins responsible for hypertrophy?

α-isoform to β-isoform of myosin heavy chain

What change in contractile proteins is associated with hypertrophy to conserve energy and produce slower, more economical contractions?

Atrial natriuretic factor (ANF)

What peptide hormone gene, expressed in both atrium and ventricle in the embryonic heart, is reexpressed in hypertrophic cells to cause salt secretion and reduce hemodynamic load?

Lysis and loss of myofibrillar contractile element (actin and myosin)

What regressive changes can occur in myocardial fibers when the muscle mass can no longer cope with the increased burden?

Heart failure

What can myocyte death, in extreme cases of hypertrophy, lead to?

Hyperplasia

What is an increase in the number of cells in an organ or tissue in response to a stimulus?

Tissues with cells that are capable of dividing

In what types of tissues does hyperplasia take place?

Hormonal hyperplasia

What type of physiologic hyperplasia occurs when there is a need to increase the functional capacity of hormone-sensitive organs?

Proliferation of glandular epithelium of the female breast at puberty and during pregnancy/lactation

What is an example of hormonal hyperplasia that also demonstrates coexisting hypertrophy?

Compensatory hyperplasia

What type of physiologic hyperplasia happens when there is a need for compensatory increase after damage or resection?

Liver regeneration after partial hepatectomy

What is an example of compensatory hyperplasia related to organ damage?

Bone marrow undergoing rapid hyperplasia in response to a deficiency of terminally differentiated blood cells

What is an example of compensatory hyperplasia in response to acute blood loss?

Excessive or inappropriate actions of hormones or growth factors

What causes most forms of pathologic hyperplasia?

Endometrial Hyperplasia

What pathologic hyperplasia involves an increase in the number of cells lining the glands or stromal cells, leading to thickening of the endometrium?

Disturbance in the balance between estrogen and progesterone

What is the cause of endometrial hyperplasia?

Abnormal uterine bleeding

What is a common clinical manifestation of endometrial hyperplasia?

Cancer of the uterus

What can endometrial hyperplasia progress to become?

Endometrium

What is the inner lining of the uterus composed of glands and stroma?

Proliferative, secretory, and menstrual phase

What are the three phases the endometrial lining undergoes?

Grossly thickened with a nodular surface

How does the endometrium appear in endometrial hyperplasia, as seen grossly?

Increased number of glands, crowding, less intervening stroma, cystically dilated glands

What histologic features characterize non-atypical endometrial hyperplasia?

Endometrial carcinoma

What does atypical endometrial hyperplasia precede?

Benign Prostatic Hyperplasia (BPH)

What pathologic hyperplasia is induced by hormonal stimulation from androgens, specifically DHT?

Nodular prostatic hyperplasia

What is another name for BPH sometimes used in pathology due to its gross and histologic appearance?

Increased prostatic acini and proliferation of stroma

What histologic features characterize BPH?

Human Papillomavirus (HPV)

What viral infection is characterized by hyperplasia where viruses interfere with host proteins regulating cell proliferation?

Skin warts (verruca) and condyloma

What are two examples of benign hyperplastic lesions caused by HPV?

Cervical carcinoma or cancer

What malignant condition can HPV also cause?

Numerous papillae or finger-like projections with a broccoli/cauliflower appearance

What gross appearance do HPV-induced lesions often exhibit?

Increase in the thickness of epithelium due to the proliferation of stratified squamous epithelium cells

What histologic change is seen in HPV?

Growth factor-driven proliferation of mature cells and increased output of new cells from tissue stem cells

What is the mechanism of hyperplasia?

Reduction in size of an organ or tissue due to decreased cell size and number

What is atrophy?

Embryonic structures like the notochord and thyroglossal duct

What undergoes physiologic atrophy during normal fetal development?

Thyroglossal duct cyst

What can develop if the thyroglossal duct does not undergo atrophy during the embryonic period?

Uterus after parturition

What organ undergoes physiologic atrophy, reverting to normal size a few weeks after pregnancy?

Decreased workload (atrophy of disuse)

What cause of atrophy is seen in a fractured bone immobilized in a plaster cast, leading to reduced muscle size?

Reversible

What is the initial decrease in cell size due to disuse, once activity is resumed?

Apoptosis

What process causes skeletal muscle fibers to decrease in number with prolonged disuse?

Loss of innervation (denervation atrophy)

What cause of atrophy results from damage to nerves, leading to atrophy of muscle fibers due to lack of stimulation?

Diminished blood supply

What cause of atrophy involves a gradual decrease in blood supply (ischemia) due to slowly developing arterial occlusive disease, such as atherosclerosis?

Progressive atrophy of the brain

What can result from reduced blood supply to the brain due to atherosclerosis affecting cerebral arteries?

Senile atrophy

What term describes the decrease in brain size in the elderly due to accumulation of fat and cholesterol in arterial lumen?

Narrowed gyri, widened sulci

What are the gross morphologic features of an atrophic brain?

Inadequate nutrition

What cause of atrophy, such as profound protein-calorie malnutrition (marasmus), leads to the utilization of skeletal muscle proteins for energy?

Cachexia

What term describes marked muscle wasting encountered in patients with chronic inflammatory diseases and cancer due to inadequate nutrition?

Tumor Necrosis Factor (TNF)

What factor is responsible for appetite suppression, lipid depletion, and muscle atrophy?

Loss of endocrine stimulation

What cause of atrophy involves the loss of estrogen after menopause or oophorectomy, leading to atrophy of the endometrium, vaginal epithelium, and breast?

Atrophic endometrium or senile cystic endometrium

What are the terms for the thinner endometrial lining resulting from decreased estrogen stimulation, often showing cystically dilated glands?