Microbiology and Pathophysiology: Inflammation and Cell Injury
Terms in this set (145)
Hyperemia is an active process resulting from:
arteriolar dilation and increased blood inflow.
Pathologic conditions can alter endothelial function, increase vascular hydrostatic pressure, or decrease plasma protein content, all of which promote
a response of vascularized tissues to infections and tissue damage that brings cells and molecules of host defense from the circulation to the sites where they are needed, to eliminate the offending agents
Inflammation is actually a protective response that is essential for survival. Removes:
microbes, toxins, and necrotic cells and tissues
(In inflammation) The mediators of defense include:
phagocytic leukocytes, antibodies, and complement proteins
The process of inflammation delivers:
leukocytes and proteins to foreign invaders, such as microbes, and to damaged or necrotic tissues
the recruited cells and molecules, which then function to eliminate the harmful or unwanted substances
Without inflammation, infections would go:
unchecked, wounds would never heal, and injured tissues might remain permanent festering sores
inflammatory reaction series number 1
The offending agent, which is located in extravascular tissues, is recognized by host cells and molecules.
inflammatory reaction series #2
Leukocytes and plasma proteins are recruited from the circulation to the site where the offending agent is located.
inflammatory reaction series #3
The leukocytes and proteins are activated and work together to destroy and eliminate the offending substance.
inflammatory reaction series #4
The reaction is controlled and terminated.
inflammatory reaction series #5
The damaged tissue is repaired.
Fast: minutes or hours/ Mainly neutrophils increase/ Usually mild and self-limited cell and tissue injury/ Prominent local and systemic signs
Slow, days/ Monocytes/macrophages and lymphocytes increase/ May be severe and progressive tissue injury/ Minimal local and systemic signs
The external manifestations of inflammation, often called its cardinal signs, are:
heat (calor), redness (rubor), swelling (tumor), pain (dolor), and loss of function (functio laesa).
In contrast, there are many diseases in which the inflammatory reaction is:
misdirected (e.g., against self-tissues in autoimmune diseases), occurs against normally harmless environmental substances that evoke an immune response (e.g., in allergies).
Inflammatory reactions underlie common chronic diseases, such as:
rheumatoid arthritis, atherosclerosis, and lung fibrosis, as well as life-threatening hypersensitivity reactions to insect bites, drugs, and toxins.
Inflammation may be responsible for diseases like:
type 2 diabetes, Alzheimer disease, and cancer.
Complement system triggers inflammatory response:
from leukocytes/ phagocytic response/ formation of membrane attack complex (mac) causing lysis of microbes
a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue
Principal Mediators of Inflammation:
Histamine/ Prostaglandins/ Leukotrienes/ Cytokines (TNF-alpha, Interleukin1, 6/ Chemokines/ Platelet activating factor (PAF)/ Complement/ Kinins
Prostaglandins and Leukotrienes are produced from:
arachidonic acid present in membrane phospholipids, which trigger the inflammatory responses
Macrophages are professional phagocytes that act as:
filters for particulate matter, microbes, and senescent cells.
Macrophages also function as effector cells that:
eliminate microbes in cellular and humoral immune responses.
Play a major role in chronic inflammation:
Eosinophils Role in Chronic Inflammation
increased in immune reactions mediated by IgE and in parasitic infection
Mast cells role in chronic inflammation
widely distributed in connective tissues and participate in both acute and chronic inflammatory reactions. Associated with IgE.
Systemic Effects of Inflammation
Fever (IL-1, TNF-alpha) mediated:
Systemic Effects of Inflammation
Systemic Effects of Inflammation
C-reactive protein (CRP), fibrinogen, and serum amyloid A (SAA) protein.
In states of chronic inflammation can, in some cases, cause:
secondary amyloidosis. CRP is marker for increased risk of myocardial infarction in patients with coronary artery disease
Systemic Effects of Inflammation:
Other manifestations of the acute-phase response include:
increased heart rate and blood pressure, rigors (shivering), chills (search for warmth), anorexia, somnolence, and malaise, probably because of the actions of cytokines on brain cells.
Factors That Impair Tissue Repair-
Infection/ Diabetes/ Nutritional status/ Glucocorticoids (steroids)/ Pressure points (Sores)/ Poor perfusion/ Foreign bodies
Can result in chronic ulcers.
Excessive scarring can lead to:
hypertrophic scars and keloids.
Cell health depends on
adequate blood supply.
the accumulation of fluid in tissues resulting from a net movement of water into extravascular space.
Blood vessels can be damaged by
the process of blood clotting that prevents excessive bleeding after blood-vessel damage.
can compromise regional tissue perfusion and, if massive and rapid, may lead to hypotension, shock, and death.
Inappropriate clotting (thrombosis) or migration of clots (embolism) can obstruct blood vessels, potentially causing ischemic cell death (infarction). This process can lead to:
myocardial infarction, pulmonary embolism (PE), and cerebrovascular accident (stroke).
migration of clots
ischemic cell death
Hyperemic tissues are redder than normal because of
engorgement with oxygenated blood.
a passive process resulting from impaired outflow of venous blood from a tissue (examples- as in cardiac failure, or locally as a consequence of an isolated venous obstruction.)
Congested tissues have an abnormal blue-red color (cyanosis) that stems from:
the accumulation of deoxygenated hemoglobin in the affected area.
an accumulation of interstitial fluid within tissues
60% of lean body weight is water,
two-thirds of which is intracellular.
Most of the remaining water is found in extracellular compartments in the form of interstitial fluid; only __________ of the body's water is in blood plasma.
Fluid can also collect in body cavities and such accumulations are often referred to collectively as:
effusions. (Pleural cavity or pericardial cavity effusion, Abdominal (peritoneal cavity ascites).
Factors controlling fluid movement within body compartments:
Vascular hydrostatic pressure and the colloid Osmotic pressure produced by plasma proteins.
Microcirculation: Arterial end pressure is high- results in:
fluid leaving the capillary into the interstitial space
Microcirculation: This is balanced by inflow at the venular end owing to:
slightly elevated osmotic pressure.
Microcirculation: There is only a small net outflow of fluid into the interstitial space, which is:
drained by lymphatic vessels.
Improper drainage results in:
Impaired venous return of the blood to the heart.
Impaired venous return of the blood to the heart.
Reduced plasma albumin (reduces capillary osmotic pressure) results in:
edema/. (Nephrotic syndrome-glomerular leaking/ Liver failure-unable to synthesize albumin/ Gut malabsorption of proteins
Lymphatic obstruction- resulting in:
lymph edema (post mastectomy)
Clinical recognition of edema:
pitting in the legs, later swelling of legs/ more serious red flag- pulmonary edema (collection of fluid in lungs, pleura)
blood loss (blood escaping from vessels) or defective clotting (hemophilia), blood thinners use. Bleed may be external/ or be subcutaneous, or inside tissues resulting in hematoma.
Petechiae are minute (1 to 2 mm in diameter):
hemorrhages into skin, mucous membranes, (due to reduced platelet count, lack of Vitamin C).
slightly larger (3 to 5 mm) hemorrhages.
larger (1 to 2 cm) subcutaneous hematomas (bruises)
Rapid loss of up to 20% of the blood volume, or slow losses of even larger amounts, may have little impact in healthy adults.
Greater losses, however, can cause:
hemorrhagic (hypovolemic) shock.
Chronic, recurrent blood loss (menstrual, GI) can result in:
iron deficiency anemia
The clotting process (Hemostasis):
A precisely orchestrated process involving platelets, clotting factors, and endothelium that occurs at the site of vascular injury and culminates in the formation of a blood clot, limits the extent of bleeding.
The clotting process (Hemostasis): Step 1
Immediate arteriole constriction- stems the blood loss.
The clotting process (Hemostasis): Step 2
Primary hemostasis: the formation of the platelet plug.
The clotting process (Hemostasis): Step 3
Secondary hemostasis: deposition of fibrin.
The clotting process (Hemostasis): Step 4
Clot stabilization and resorption.
Excessive tendency to clot formation
Blood clotting acquired causes
1. Prolonged bed rest, immobilization (stasis)
2. Heart attack
3. Atrial fibrillation
5. Prosthetic cardiac valves
6. Pregnancy, Oral contraceptives (Estrogen)
Fate of the Thrombus:
from Veins to lungs (Pulmonary emboli)
Arterial (Systemic) embolus-
causes anoxia and gangrene (75% in legs/ 10% in CNS)
following crush injuries
A altered state of body caused by reduced cardiac output I.e. pump failure
decrease blood volume
Cardiogenic and Hypovolemic shock effect
The effect would be decreased tissue perfusion and hypoxia.
Severe systemic inflammatory response syndrome
systemic vasodilation and increased vascular permeability that is triggered by hypersensitivity reaction.
Stage of shock: An initial non-progressive stage -
reflex compensatory mechanisms try to maintain vital signs
Stage of shock: A progressive stage-
resulting in hypoperfusion, and acidosis
Stage of shock: An irreversible stage-
so severe that even if the hemodynamic defects are corrected, survival is not possible.
In hypovolemic and cardiogenic shock, patients exhibit:
hypotension, a weak rapid pulse, tachypnea, and cool, clammy, cyanotic skin.
In septic shock, the skin may be:
warm and flushed owing to peripheral vasodilation.
causes and modifying factors that are responsible for the initiation and progression of disease. Causes can be multifactorial
the mechanisms of development and progression of disease
Functions of a living cell-
Maintain homeostasis between itself (intracellular) and the environment (extracellular).
Responds to external signals via receptor activity.
Manufacture necessary proteins required by the body.
Utilize energy for this process and for expelling waste products.
Passive Membrane Diffusion-
fat soluble substances easily cross / small molecules (water, urea)
Barrier to glucose, electrolytes -
require carriers and channels (helps cell nutrition uptake and waste disposal)
create hydrophilic pores that, when open, permit rapid movement of small, charged solutes. Slow process.
can create drug resistance
Cells are 'hypertonic'
risk of over hydration-osmosis
prevents cells from becoming hypertonic
Regulate intracellular pH
enzymes like pH7.4; lysosomes like pH4.7
'balance' between synthesis/ degradation
Rough ER- translate mRNA to manufacture proteins, fold them properly (disulfide bonds) improper folding (misfolding) (mutation) : familial hypercholesterolemia/ cystic fibrosis
Misfolding 'overwhelms' ER-
causes ER stress response and leads to cell death
recycles, exports cell products (mucus, antibodies), modify toxins in the liver
Waste disposal: Lysosomes-
40 different acidic enzymes (pH4.7) proteases, nucleases, lipases, glycosidases, phosphatases, and sulfatases. Catabolic enzymes.
Cell debris is digested (___________________) Role in cell preservation or death (_________________________)
play an important role in degrading cytoplasmic proteins, controlling ½ life of proteins. Breaks them into smaller chains of amino acids and recycled.
Cells ability to respond to stress or injury determines the
outcome of the cell health
Role of Growth factors in health/ disease
Epidermal growth factor (EGF)
Transforming growth factor-α (TGF-α)/ (TGF-β)
Hepatocyte growth factor (HGF) (scatter factor)
Vascular endothelial growth factor (VEGF)
Platelet-derived growth factor (PDGF)
Fibroblast growth factors (FGFs), including acidic (FGF-1) and basic (FGF-2)
Keratinocyte growth factor (KGF) (i.e., FGF-7)
" Damage to cells is the basis of:
Work overload/ Lack of nourishment
a process to stay viable and be functional.
Inability to adapt results in: (Reversible? or Irreversible??)
If cell injury is irreversible, results in
cell death by necrosis or apoptosis.
Causes for cell injury/ death:
Hypoxia/ Ischemia/ Toxins/ Infectious agents
Immune responses; reactions/ Genetic defects
Nutritional causes/ Physical agents
'Accidental cell death'
'Cell signal death'-
Apoptosis (regulated by specific gene p53)/ Also a natural process used by healthy tissues to maintain cell balance. (Programmed cell death)
Cells lose function long before
cell death occurs. They may be salvaged by interventions and can be made viable.
Necrosis leads to:
inflammation, an enzymatic process to eliminate the cell debris, and this leads to repair process.
Distinct patterns of tissue necrosis may provide etiologic clues:
These terms are used by pathologists and clinicians in their report
The underlying tissue architecture is preserved for at least several days after death. the dead cells are ultimately digested by the action of lysosomal enzymes of the leukocytes.
This type of necrosis is characteristic of infarcts (areas of necrosis caused by ischemia) in all solid organs except the brain.
Seen in focal bacterial and, occasionally, fungal infections because microbes stimulate rapid accumulation of inflammatory cells, and the enzymes of leukocytes digest ("liquefy") the tissue and transforming the tissue into a viscous liquid that is eventually removed by phagocytes. "PUS"
This term commonly used in clinical practice. It usually refers to the condition of a limb hat has lost its blood supply and has undergone coagulative necrosis involving multiple tissue layers. Remains dry, but when infected by bacteria results in pus and is known as 'wet gangrene'.
Caseous means "cheese like," ('friable white-yellow appearance'). This is most often encountered in foci of tuberculous infection.
Focal areas of fat destruction, typically seen in cases of pancreatitis resulting in leakage of pancreatic enzymes digesting the peritoneal fat. The released fatty acids combine with calcium to produce grossly visible chalky white area.
It usually occurs in immune reactions in which complexes of antigens and antibodies are deposited in the walls of blood vessels. (Hypertension, Temporal arteritis)
Causes of Apoptosis:
Serves to eliminate potentially harmful cells and cells that have outlived their usefulness. Also, when the damage affects the cell's DNA or proteins; thus, the irreparably damaged cell is eliminated.
ensures unwanted cells are eliminated without eliciting potentially harmful inflammation. (Could cause autoimmune diseases if they were not purged.)
occurs after exposure to radiation and cytotoxic drugs. (Accumulation of misfolded proteins also triggers apoptotic death.)
Autophagy ("self-eating") refers to:
lysosomal digestion of the cell's own components. Frequently seen in ischemic situations. It is a survival mechanism in times of nutrient deprivation, so that the starved cell can live by eating its own contents and recycling these contents to provide nutrients and energy. An adaptation that helps cells survive lean times.
Oxidative process results in reactive oxygen species (ROS)-
'free radicals' (single unpaired electron) ( Seen in chemical and radiation injury, hypoxia, cellular aging, tissue injury caused by inflammatory cells, and ischemia-reperfusion injury.)
Glutathione is a powerful
Physiologic adaptations to stress-
the hormone-induced enlargement of the breast and uterus during pregnancy/ mechanical stress (in the case of bones and muscles).
Increase in the size of cells resulting in an increase in the size of the organ. (occurs when cells have a limited capacity to divide.)
Is an increase in cell number. (an adaptive response in cells capable of replication)
Is the cardiac enlargement that occurs with hypertension or aortic valve disease.
"Shrinkage in the size of cells by the loss of cell substance."
Cellular atrophy results from a combination of
decreased protein synthesis and increased protein degradation.
Cells may have diminished function, but they are not dead.
Examples of atrophy-
disuse atrophy of muscle/ lack of blood supply/ lack of nourishment/ menopause
"A change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type."
Examples of metaplasia:
Change that occurs in the respiratory epithelium of habitual cigarette smokers. (columnar epithelial cells of the trachea and bronchi often are replaced by stratified squamous epithelial cells)/ in chronic gastric reflux(GERD), the normal stratified squamous epithelium of the lower esophagus may undergo metaplastic transformation to gastric or intestinal-type columnar epithelium (Barrett's esophagus).
Metaplastic change in an epithelium, if persistent, may:
predispose to malignant transformation.
Causes for Cellular Aging:
• Cumulative DNA damage
• Reduced cellular replication (Telomerase dependent)
• Disrupted protein homeostasis
• Calorie excess (Calorie restriction slows down aging)
• Lack of exercise (Exercise slows down aging)
• Persistent inflammation
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