PATHO - Cell Growth and Adaptation

Cell Growth

The process of increase in cell size as a result of synthesis of specific tissue components (such as ground substances, extracellular matrix, and subcellular organelles).

Multiplicative

Increase in number of cells through the process of mitotic cell division. No increase in cell size. Present in all tissues during embryogenesis

Auxetic

Increase in the size of an individual cell. No increase in cell number

Accretionary

Increase in intercellular tissue components such as: Collagen, Extracellular component, Ground substance, Elastin. No increase in cell size and cell number, only an increase in the amount of space between cells. Typically found in growing and developing bones and cartilages

Combined pattern

Combination of multiplicative, auxetic, and accretionary growth

Cell Differentiation

Process where a cell develops a specialized function or morphology that distinguishes it from its parent cell. Process by which genes are expressed selectively and gene products act to produce a specialized or overt cell

Proliferation, Differentiation, Apoptosis

What are the potential fates of cells?

Labile Cells

Continuously divide throughout the post-natal life. Have a shorter life span due to rapid cell turnover. Continuously replenish

Stable Cells

Divide infrequently under normal conditions; Divide only when needed. When lost, their stem cells are easily stimulated to differentiate or divide

Permanent Cells

Do not divide throughout the post-natal life. Can no longer be replaced or regenerated if damaged

Growth Factors

Polypeptides necessary for cell proliferation. May have single or multiple cell targets. May promote cell survival, locomotion, contractility, differentiation, and angiogenesis

Epidermal Growth Factor (EGF)

Functions: Mitogenic for keratinocytes and fibroblasts. Mitogen = initiates mitosis. Stimulates keratinocyte migration and granulation tissue formation (growth of epithelium)

Transforming Growth Factor-a (TGF-a)

Functions: Similar to EGF. Stimulates replication of hepatocytes and most epithelial cells

Hepatocyte Growth Factor-a (HGF-a) (aka HGF/SF)

Functions: Enhancing proliferation of: Hepatocytes, Epithelial cells of kidneys, Lungs, Breast, Skin, Endothelial cells. Increases cell motility, keratinocyte replication

Platelet Derived Growth Factor (PDGF)

Functions: Causes migration and proliferation of fibroblasts, smooth muscle cells, and monocytes to the area of inflammation and healing skin wounds. Chemotactic for PMNs, macrophages, fibroblasts, and smooth muscle cells ;activates PMNs, macrophages, and fibroblasts. ● Mitogenic for fibroblasts, endothelial cells, and smooth muscle cell contraction. Stimulates production of MMPs, fibronectin, and HA; stimulates angiogenesis and wound contraction

Vascular Endothelial Growth Factor (VEGF)

Dimeric glycoprotein with multiple isoforms (VEGF-A, VEGF-B, VEGF-C, VEGF-D and PIGF). Functions: Promotes angiogenesis. Increases vascular permeability. Stimulates endothelial cell migration & proliferation. VEGF-C selectively induces hyperplasia of lymphatic vasculature. Upregulates endothelial expression of plasminogen activator, plasminogen activator inhibitor 1, and collagenase

Fibroblast Growth Factor

Has > 20 members but FGF-1 and FGF-2 are the best characterized. Functions: Wound repair. Angiogenesis. Hematopoiesis. Development of: Skeletal and cardiac muscles, Lung maturation, Specification of the liver from endodermal cells

Transforming Growth Factor-B (TGF-B)

Isoforms: TGF- β1, TGF- β2, TGF- β3. Functions: Chemotactic for PMNs, macrophages, lymphocytes, fibroblasts, and smooth muscle cells. Stimulates TIMP synthesis, angiogenesis, and fibroplasia. Inhibits production of MMPs and keratinocyte proliferation (blocks the cell cycle). Regulates integrin and cytokine expression - strong anti-inflammatory effect

Cytokines

Protein mediators of inflammation and immune response. Have growth-promoting activities for a variety of cells

Signaling Mechanisms

Receptor-mediated signal transduction. Binding of ligands to specific receptors. Receptor activation leads to expression of specific genes

Autocrine

Cells respond to signaling molecules they themselves secrete, hence, creating an autocrine loop

Paracrine

One cell produces the ligand which acts on the adjacent target cells that express the appropriate receptor. The adjacent cell is of different type from the cell expressing the ligand

Endocrine

An endocrine gland produces hormone targeting distant cells, usually carried out by blood

Cellular Adaptations

Reversible changes in size, number, phenotype, metabolic activity, or functions of cells in response to changes in their environment. Achieve a new but altered steady state to preserve the cell’s viability. Main goal is to achieve homeostasis,

Hypertrophy

Increase in size with resultant increase in the size of organ, mass and protein. Most important/common stimulus: increased workload

Increase in cell’s structural components and cellular proteins

What is the main mechanism in hypertrophy?

Physiologic Hypertrophy

Influenced by hormones and growth factors. Ex: skeletal muscles of body builders, smooth muscle cells of uterus during pregnancy

Pathologic Hypertrophy

A type of hypertrophy Influenced by existing medical condition/disease or a chronic hemodynamic overload

Myocardial Hypertrophy

Secondary to hypertension and defective heart valves. Constricted blood vessels require increased pressure to push blood through narrow lumen, causing hypertension

Selective Hypertrophy

Subcellular organelles develop hypertrophy. Ex: hypertrophy of smooth endoplasmic reticulum in the hepatocytes in patients treated with barbiturate. This increases cytochrome P450 to detoxify drugs via oxidation

Hyperplasia

Increase in number of cells in an organ or tissue. Usually results in an increased mass of the organ or tissue. Occurs in cells capable of dividing. May co-exist with hypertrophy triggered by the same external stimulus

Result of growth factor-driven proliferation of mature cells

What is the main mechanism of hyperplasia?

Hormonal Hyperplasia

Occurs when there is a need to increase the functional capacity of hormone-sensitive organs. Ex: Increase in number of glands during puberty and pregnancy. During pregnancy, female body prepares the breast for future breastfeeding by increasing the number of breast lobules for greater milk production

Compensatory Hyperplasia

Occurs after damage or partial resection. Ex: After a partial hepatectomy, the remaining hepatocytes increase in number and assume the normal appearance and size of the liver. Part resected is not replaced; liver is restored in appearance only. Ex: This also occurs in a partial nephrectomy

Pathologic Hyperplasia

Caused by excess of hormones or growth factors acting on target cells. Ex: endometrial hyperplasia, benign prostatic hyperplasia, viral infections of the skin

Endometrial Hyperplasia

Normally, endometrium is thinner for the elderly woman undergoing menopause caused by hormone withdrawal. However, some pathologies can cause hormonal production to continue, causing

Atrophy

Decrease in cell size of organ or tissue resulting from decrease in cell size, mass, and number. May be physiologic or pathologic atrophy

Decreased protein synthesis but increased protein degradation in cells

What is the main mechanism of atrophy?

Ubiquitin-Proteosome Pathway (UPP)

In atrophy, there is decreased protein synthesis but increased protein degradation in cells giving products of degradation. The degraded substances, especially protein, will be removed from the body via the?

Autophagy

Means self-eating

Autophagic vacuoles

Are membrane-bound vesicles or vacuoles containing fragments of cell components. Fuses with lysozymes so that the contents will be degraded through the action of the lysosomal enzyme but not 100% will be get rid of the products of degradation

Physiologic Atrophy

Tissues/structures present in embryo, fetus or childhood may undergo atrophy as growth and development progress. Ex: Webbing of the hands and feet, thymus. Ex: If the thyroglossal duct does not involute or atrophy, it will turn into a cyst

Pathologic Atrophy

Occurs as a result of disease or loss of trophic support. Can also be caused by: Decreased workload (atrophy of disuse), Denervation atrophy, Diminished blood supply, Inadequate nutrition, Loss of endocrine stimulation, Pressure from enlarging tumor

Brain atrophy

Characterized by narrow gyri and widened sulci. More prone to vascular tears due to spacious cranium, secondary to brain atrophy

Metaplasia

Differentiated cell is replaced by another cell type in response to an altered environment state (ex: chronic cellular injury and repair). Often associated with a greater risk of malignancy, especially when it is continuous

Reprogramming of stem cells existing in normal tissues

What is the main mechanism of metaplasia?

Squamous Metaplasia

Most common type of metaplasia. Columnar to squamous cells

Columnar Metaplasia

Squamous to columnar. Barrett’s esophagus: cells are stimulated by repeated gastric acid reflux

Connective tissue Metaplasia

Formation of mesenchymal tissues in tissues that do not usually contain those elements

Dysplasia

Abnormal organization of cells. Characterized by increased cell proliferation and atypical morphology. It may be reversible only in the early stages

Hypertension

C.K., 50 y.o., male, consulted an out-patient physician due to 2 months history of dizziness, headache, and intermittent chest heaviness. BP was noted to be 160/100 mmHg. Lipid profile shows increased LDL, cholesterol, triglyceride, and decreased HDL.

What is the offending stimulus?

Heart

C.K., 50 y.o., male, consulted an out-patient physician due to 2 months history of dizziness, headache, and intermittent chest heaviness. BP was noted to be 160/100 mmHg. Lipid profile shows increased LDL, cholesterol, triglyceride, and decreased HDL.

What is the primary organ affected?

Hypertrophy

C.K., 50 y.o., male, consulted an out-patient physician due to 2 months history of dizziness, headache, and intermittent chest heaviness. BP was noted to be 160/100 mmHg. Lipid profile shows increased LDL, cholesterol, triglyceride, and decreased HDL.

What is the expected cellular adaptation?

Increase in protein synthesis and structural proteins

C.K., 50 y.o., male, consulted an out-patient physician due to 2 months history of dizziness, headache, and intermittent chest heaviness. BP was noted to be 160/100 mmHg. Lipid profile shows increased LDL, cholesterol, triglyceride, and decreased HDL.

What is the mechanism of cellular adaptation?

Pathologic (Hypertension)

C.K., 50 y.o., male, consulted an out-patient physician due to 2 months history of dizziness, headache, and intermittent chest heaviness. BP was noted to be 160/100 mmHg. Lipid profile shows increased LDL, cholesterol, triglyceride, and decreased HDL.

Is it physiologic or pathologic?

Intramural myomatous mass

Y.S.L., 36 y.o., 40kg, underwent transvaginal ultrasound due to mild abdominal pain and enlargement. A 10cm intramural myomatous mass is seen. She underwent hysterectomy.

What is the offending stimulus?

Uterus

Y.S.L., 36 y.o., 40kg, underwent transvaginal ultrasound due to mild abdominal pain and enlargement. A 10cm intramural myomatous mass is seen. She underwent hysterectomy.

What is the primary organ affected?

Atrophy

Y.S.L., 36 y.o., 40kg, underwent transvaginal ultrasound due to mild abdominal pain and enlargement. A 10cm intramural myomatous mass is seen. She underwent hysterectomy.

What is the expected cellular adaptation?

Decreased protein synthesis and increased protein degradation

Y.S.L., 36 y.o., 40kg, underwent transvaginal ultrasound due to mild abdominal pain and enlargement. A 10cm intramural myomatous mass is seen. She underwent hysterectomy.

What is the mechanism of cellular adaptation?

Pathologic (myomatous mass)

Y.S.L., 36 y.o., 40kg, underwent transvaginal ultrasound due to mild abdominal pain and enlargement. A 10cm intramural myomatous mass is seen. She underwent hysterectomy.

Is it physiologic or pathologic?

Homeostasis

The ultimate goal of cellular adaptation is to achieve ________

Permanent

Based on the cell’s proliferative potential, neurons are considered __________ cells.

Paracrine

A cell sending signal to adjacent different cell type to proliferate is an example of _________ signaling mechanism.

Hypertrophy

What type of cellular adaptation is expected in the heart of a patient with long standing uncontrolled hypertension?

Squamous

What is the most common type of epithelial metaplasia?

Physiologic

A liver that assumes its original size after partial hepatectomy demonstrates what type of hyperplasia (physiologic or pathologic)?

Narrow; Widened

An atrophic brain has __________ gyri and ____________ sulci.

Labile

Based on the cell’s proliferative potential, red blood cells are considered __________ cells.

Endocrine

A cell sending signal to remote organs to proliferate is an example of _________ signaling mechanism.

Columnar Metaplasia

What type of cellular adaptation is expected in a patient with GERD?