Alterations to Normal Cellular Function Flashcards
Cell Homeostasis
The normal cell is a restless pulsating structure, constantly modifying its organization and function in response to changing demands and stress. If the cell suffer from excessive stress it can undergo adaptation preserving health of the cell despite continued stress.
Cell Injury
If no adaptive response is possible or the cell’s adaptive capability is exceeded, cell injury develops. Cell injury is reversible up to the certain point, but in the case of persistent and severe stress the cell suffers irreversible injury and die.
Causes of Cell Injury
- Hypoxia
- Physical Agents
- Chemical Agents & Drugs
- Infectious Agents
- Immunologic Reactions
- Genetic Defects
- Nutritional Imbalances
- Hypoxia
Decreased availability of O2 needed in cells. Blood unable to deliver O2 where needed.
Causes of Hypoxia
A) Ischemia
B) Cardiopulmonary Failure
C) Loss of oxygen carrying capacity of the blood
A) Ischemia
Most common cause: Obstructed blood flow. Arterial flow or venous drainage obstructed by vascular diseases -> loss of blood supply to tissues. Distal areas suffer most because blood doesn’t get to peripheral parts.
B) Cardiopulmonary Failure
lack of oxygenation of blood. Lungs not doing their job. Blood can reach periphery but lacks O2
C) Loss of O2 carrying capacity of blood
EXAMPLES: Anemia or CO poisoning.
If not enough hemoglobin/RBCs = anemia.
OR Sickle cell - weird shape doesn’t allow for easy binding of O2 to hemoglobin.
-Hemoglobin = iron + protein. Lacking iron means can’t synthesize hemoglobin. OR if bone marrow not producing enough RBCs.
Lack of production of B12 = lacking intrinsic factor in gut. Leads to pernicious anemia and that causes hypoxia. Have to bypass gut with B12 - need to go directly into bloodstream. If too much blood is too thick and leads to ischemia.
Causes of Cell Injury
- Physical Agents (examples)
A) Mechanical trauma - any physical trauma
B) Extremes of heat or cold -
C) Sudden changes in atmospheric pressure - Nitrogen in blood can turn from gas into liquid form that can lead to obstructed blood flow (ischemia). Scuba diving - coming back up and not slow adjustment = the bends?
D) ionizing radiation - formation of OH radicals -
E) electric energy
Causes of Cell Injury
- Chemical Agents and Drugs
Virtually any chemical agent or drug, even a substance such as glucose may generate cell adaptation, injury or death. (water)
Act on vital cell functions - membrane permeability, osmotic homeostasis, or integrity of different enzymes or cofactors.
EXAMPLES: mercury, salts, trace amounts of agents (poisons), air pollutants, insecticides, herbicides, recreational and therapeutic drugs.
Causes of Cell Injury
- Infectious Agents (examples)
A) Viruses
B) Rickettsiae - bacteria often carried by small insects (ticks, fleas and lice) WHY ITS OWN CATEGORY?
C) Bacteria
D) Fungi - nearly untreatable.
E) Parasites.
Causes of Cell Injury
- Immunologic reactions (3 types)
Immune system overdoes it and attacks
A) Anaphylactic reaction to the foreign proteins - Shock = quick drop in blood pressure.
B) Deposition of immune complexes - to neutralize invader (antigen) by forming complex. Tissue recognizes complex as foreign body - attacks and causes inflammation. Tissue becomes less functional.
C) Autoimmune reactions - Body recognizes its own as enemy. Similar to B but doesn’t form complex (myasthinia gravis). Antibodies acting on own tissue and preventing it from acting normally. Examples: Psoriasis. Multiple Sclerosis.
Causes of Cell Injury
- Genetic Defects (2 types)
May result in gross defects or subtle alterations in protein structure
A) Congenital malformations
Monosomy / Trisomy
B) Chromosomal (DIPT)
-Deletions - Losing piece of lineup.
-Insertions - A piece of another chromosome inserted into another one.
-Point mutations - changing a single base nucleotide
-Translocations - arrangement of parts between nonhomologous chromosomes
Causes of Cell Injury
- Nutritional Imbalances (4 types)
-
Protein-calorie deficiencies - marasmus (lack of calories) and kwashiorkor (lack of protein but enough energy intake)
* hypoproteinemia → less protein in blood, more water → bulging stomach with skinny limbs
-
Protein-calorie deficiencies - marasmus (lack of calories) and kwashiorkor (lack of protein but enough energy intake)
- Dietary excesses - strongly implicated in atherosclerosis and obesity.
-
Vitamin deficiencies (avitaminoses)
* Pernicious anemia: A decrease in red blood cells when the body can’t absorb enough vitamin B12; doesn’t have enough intrinsic factors that stomach makes
-
Vitamin deficiencies (avitaminoses)
- Vitamin excesses (hypervitaminoses)
MECHANISMS OF CELL INJURY
If the stress is removed in time full cell integrity can be restored. Characteristics of acute cell injury are:
- cell swelling - first manifestation of cell injury.
- mitochondrial swelling
- plasma membrane alterations
- dilation of ER
- nuclear alterations
If stress removed in time - it will be restored (reversible)
MECHANISMS OF CELL INJURY
Steps to Cell Injury
Less oxygen -> Less ATP ->
A) More anaerobic glycolysis -> lactic acidosis -> lowering pH -> clumping of chromatin in nucleus
B) Na-K pump dysfunctions -> cell, ER swelling due to Na/water accumulation, loss of microvilli
C) Detachment of ribosome -> reduced amount of protein synthesis
MECHANISMS OF CELL INJURY
Cell Swelling
Mitochondrial oxidative phosphorylation stopped/slowed due to hypoxia = less ATP
Causes:
-Decrease in Na-K pump leading to accumulation of Na and Cl which leads to accumulation of water and acute cellular swelling.
MECHANISMS OF CELL INJURY
Characteristics of IRREVERSIBLE Acute Cell Injury
- Excessive damage of plasma membrane
- Vacuolization (formation of vacuoles) of mitochondria
- Swelling of lysosomes
- massive calcium influx into cell - extremely damaging.
- Release of oxygen free radicals - Missing one electron. Becomes unstable and wants to borrow electron. Destroys surrounding tissue.
MECHANISMS OF CELL INJURY
Calcium Influx into Cell and Its Effects
Damage to ER, mitochondria (first) and cell membrane (later) leads to increase in Ca++.
Causes:
1. Increased Mitochondria permeability (can lead to apoptosis due to release of cytochrome C)
2. Activating enzymes (4)- ATPase (ATP depletion), phopholipase (break down phospholipid membrane), protease (break down protein - cell membrane detaches from cell - succeptible to stretching and rupturing), endonuclease (DNA damage)
MECHANISMS OF CELL INJURY
3 Causes of Cell Membrane Damage
- progressive loss of membrane phospholipids (Ca++)
- cytoskeletal abnormalities (Ca++)
- toxic oxygen radicals
MECHANISMS OF CELL INJURY
- Toxic oxygen radicals
Radicals increased in ischemic tissues especially upon restoration of blood flow, and may be cause of reperfusion injury (tissue damage caused when blood returns after period of ischemia).
This cause of cell injury is emerging as a final common pathway of tissue damage in such processes as:
- chemical and radiation injury
- oxygen and other gaseous toxicity
- cellular aging
- microbial killing by phagocyte cells
- inflammatory damage
MECHANISMS OF CELL INJURY
How Oxygen Free Radicals damage cells initiate a number of autocatalytic reactions, but three are particularly relevant to cell injury:
- Lipid peroxidation - Results in loss of membrane integrity.
- Lesions in deoxyribonucleic acid (DNA) - Can cause cell death or malignant transformation.
- cross-linking of amino acids - Leads to eventual degradation of protein
2 Types of Cell Death
- Necrosis
- Apoptosis
- Apoptosis
Genetically pre-programmed cell death.
Apoptosis is probably responsible for a number of physiologic events like programmed destruction of cells during embryogenesis, hormone dependent involution of endometrium during menstrual cycle.
Can be triggered by pathologic stimuli such as irradiation and virus infections, like in viral hepatitis where apoptotic cell fragments, called Councilman bodies can be found in the liver.
