Patho chapter 2

chapter 2

Injury to cells and the ECM leads to what

Tissue and organ injury.

Cellular adaptation is what?

AN adaptation is an alteration that enables the cell to maintain a steady state despite adverse conditions

What are the significant adaptive changes for cells?

Atrophy, hypertrophy, hyperplasia, and metaplasia. Dysplasia is not a true cellular adaption

What is Atrophy?

A decrease in cellular size which can affect any organ but is most common in skeletal muscle, the heart, sex organs, and the brain. It is caused by disuse, poor blood supply, decreased amino acid uptake, or insufficient neural stimulation

Physiologic (normal) atrophy occurs when?

With early development. The thymus gland involutes for example.

What atrophies due to aging?

brain cells and endocrine-dependent organs like glands

What is Hypertrophy?

An increase in cell size caused by increased work load or hormonal stimulation. It can cause increased protein in the plasma membrane, endoplasmic reticulum, microfilaments, or mitochondria.

Hyperplasia is what?

An increase in cell number caused by increased rate of cellular division. The mechanism for this cause is the production of hormones or growth factors. types of hyperplasia include compensatory, which allows certain organs to regenerate, or hormonal hyperplasia which occurs chiefly in estrogen-dependent organs to replace lost tissue or support new growth such as in pregnancy.

Pathologic hyperplasia is what?

Abnormal proliferation of normal cells in response to excessive hormonal stimulation or the effects of growth factors on target cells

Dysplasia (atypical hyperplasia) is what?

An abnormal change in the size, shape, and organization of mature tissue cells. NOT CANCER. Dysplastic tissues that do not involve the entire thickness of the epithelium may be reversed.

Metaplasia is what?

the reversable replacement of one mature cell type with another. Common in cases of tissue damage, repair, and regeneration. It reprograms local tissue stem cells or causes colonization by different adjacent cell populations.

What can be causes of cell damage?

hypoxia, free radicals, caustic or toxic chemicals, infectious agents, direct injury, inflammatory or immune response, genetic factors, malnourishment.

What are the different types of cell injury? (classifications)

Acute or chronic, reversible or irreversible. May involve necrosis, apoptosis, autophagy, accumulation, or pathologic calcification.

What are the four biochemical themes important to cell injury?

1. Depletion of ATP

2. Hypoxia or increase in oxygen-derived free radicals

3. increase in concentration of intracellular calcium

4. defects in membrane permeability

What is the common sequence of events leading to cell death?

1. decreased ATP

2. failure of active transport mechanisms

3. cellular swelling

4. detachment of ribosomes

5. cessation of protein synthesis

6. mitochondrial swelling from calcium accumulation

7. vacuolation (formation of vacuoles in or near cell)

8. Leakage of digestive enzymes from lysosomes

9. autodigestion of internal cell structures

10. lysis of the plasma membrane

the initial insult in hypoxic injury is usually what?

Ischemia, which is the cessation of blood flow into vessels that supply the cell. Hypoxia, by this mechanism, causes inflammation which can form hypoxic lesions.

What is reperfusion?

The restoration of oxygen supply following ischemic injury. This can result in reperfusion injuries caused by the highly reactive oxygen intermediates or radicals which further increase inflammatory neutrophil adhesion to the endothelium

what are ROS?

Reactive oxygen species. they form from aerobic metabolism and play a key role in normal biology, like cell communication, and various disease processes.

What is the role of reduction-oxidation (REDOX) dependent regulation and ROS?

normal physiologic and pathologic functions including proliferation, differentiation, immune function, stem-cell renewal, tumor progression, autoimmunity, stem-cell exhaustion, senescence, and logevity.

What conditions cause damage by free radicals, including ROS?

chemical and radiation injury, ischemia-reperfusion injury, aging

What is oxidative stress and how does it damage the membrane?

oxidative stress is an imbalance between ROS and antioxidants in the body. IT activates several intracellular signaling pathways due to ROS modulating enzymes and transcription. free radicals, related to ROS, cause chain reactions.

What are key sources of “oxidants”?

Cellular organelles like mitochondria, endoplasmic reticulum, and the peroxisomes. Additionally NADPH oxidases and other enzymes are key sources.

What is the mechanism by which free radicals damage cells?

Lipid peroxidation, or destruction of unsaturated fatty acids, alterations of proteins and protein loss and protein misfolding, mutations to DNA

What is mtDNA?

mtDNA is mitochondria DNA responsible for encoding proteins involved in energy production, enzymes involved in oxidative phosphorylation.

What areas are most hurt by damage to mtDNA?

Organs dependent on oxidative phosphorylation like the CNS, skeletal muscle, cardiac muscle, liver and kidneys.

What are the pathways that toxicity, damaging toxins, affects health?

the pathways include oxidative stress, heat shock response, DNA damage response, hypoxia, ER stress, mental stress, inflammation, and osmotic stress

What is the initial insult, damage done by chemical and toxic injury?

Damage to the plasma membrane. This happens through direct toxicity or conversion into toxic intermediates or metabolites.

How many snake bites occur in the world and united states annually?

4.5 to 5.5 million people get bit annually, with most bites in the United States being from pit vipers. The rattle snake is the most common pit viper bite in the United states.

What is the single largest enviroment health risk in the world?

air pollution. it is the fourth leading risk factor for premature death

What are the six pollutants as criteria for air pollutants?

carbon monoxide, lead, nitrogen oxides, photochemical oxidants, ground-level ozone particle, sulfur oxides. levels higher than PM2.5 pose the greatest risk

How do heavy metals affect cellular function?

impair DNA repair, tumor suppression, and signal transduction pathways

how do genetic disorders injure cells?

altering the nucleus and the plasma membranes structure, shape, receptors, or transport mechanisms

How does malnurishment affect cells?

By altering cellular structure and function. Particularly the transport mechanisms, chromosomes, the nucleus, and DNA

What are manifestations of celular injury

accumulation of water, lipids, carbs, glycogen, proteins, pigments, hemosiderin, bilirubin, calcium, and urate. These hurt the cell by crowding the organelles and causing excessive metabolites to be produced.

What is cellular swelling?

The accumulation of excessive water in the cell, caused by the failure of transport mechanisms

What causes the accumulation of organic substances?

lipids, carbs, glycogen, proteins, and pigments accumulate when cellular update exceeds the cells ability to digest them or cellular anabolism exceeds the cells needs

How do calcium salts accumulate in cells (Dystrophic calcification)?

hypercalcemia. this leads to calcium hardening thus interfering with normal cellular structure and function by activation of protein kinases, phospholipases, and membrane damage.

What is gout?

The accumulation of urate , in the form of sodium urate crystals, in the tissue

What are SYSTEMIC manifestations of cellular injury?

Fever, leukocytosis, tachycardia, pain, and elevated serum enzymes and plasma.

What are the two types of cell death?

accidental cell death (ACD), or regulated cell death (RCD. Traditionally classified as necrosis and apoptosis

What is ACD or necrosis?

unintentional cell death. characterized by rapid loss of the plasma membrane, organelle swelling, mitochondrial dysfunction

What is RCD or apoptosis?

intentional cell death. characterized by dropping off of cell segments, called apoptotic bodies. can be caused by oxidative stress.

what are the five types of necrosis?

1. coagulative

2. liquefactive

3. caseous

4. fat

5. fibrinoid

What is gangrenous necrosis?

tissue necrosis caused by hypoxia and subsequent bacterial invasion

What is autophagy?

a recycling factory, self-destructive process, and survival mechanism. It degrades the cytoplasmic components and organelles using lysosomes then salvages key nutrients

What is againg?

a time dependent decline. the hallmarks are genomic instability, telomere attrition, epigenetic alterations, and loss of protein homeostasis, deregulated nutrient sensing, mitochondrial dysfunction, stem cell exhaustion, and altered cell communication

What is senescence?

the process of permanent proliferative arrest.

What is the inherent max life for humans?

80 to 100 years

What is somatic death?

death of an entire organism. postmortem change is diffuse and does not involve the inflammator response

What is the sequence of somatic (organism death)?

1. pallor mortis

2. algor mortis

3. rigor mortis

4. livor mortis

5. putrefaction

6. decomposition

7. skeletonization

What is the rare eight stage of somatic death (organism death)?

fossilization, depends on the environment of the organism