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Definition
it is a causative agent that can be genetic or acquired.
there may be an overlap since there are genetic predisposition's to certain acquired diseases and environmental factors that affect certain genetic diseases. |
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Definition
The sequence of biochemical, morphological and immunological responses to an etiological agent.
The progression of the disease. |
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Term
| What is the expression of pathology? |
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Definition
| The biomechanical, morphological and functional expressions that lead to the clinical manifestations of a pathology. |
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Definition
An increase in cell size.
These cells are typically amitotic and thus respond to increased demand by increasing the number of myofibrils, glycolytic and/or oxidative enzyme stores and inclusions such as ATP and glycogen |
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| Discuss Physiological Hypertrophy in regards to Mechanical and hormonal triggers. |
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Definition
Mechanical Triggers:
-Induced by a functional stress such as increased work load
-Mechanism of Cardiac Hypertrophy
-Mechanical triggers such as chronic hemodynamic overload are transduced by the cell leading to transcription of contractile proteins within the myocyte
Hormonal Triggers:
-Induced by tropic stimulation of a target tissue that leads to increased synthesis of cellular structures.
-Mechanism of gravid uterine hypertrophy
-Increases in smooth muscle cell size is stimulated by estrogenic hormones |
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Definition
Induced by conditions of disease
-can be either compensatory or adaptive |
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| Define Compensatory Hypertrophy and give examples |
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Definition
The increased function or enlargement or an organ to compensate for the loss of a paired organ or similar tissue.
-Post-polio syndrome: fibers innervated by somatic anterior horn cells underwent compensatory hypertrophy after initial exposure and damage leading to fatigue years later
-Nephrons: if a nephron is damaged they will not regenerate by instead remaining nephrons will hypertrophy |
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| Define Adaptive Hypertrophy and give examples |
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Definition
Organ or tissue increases in response to an increased functional demand
-Myocardial: an increase in ventricular mass in response to CHF or hypertension |
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Definition
A decrease in cell size related to reduction of structural components
-typically related to decreased stimulation or decreased nutrients
-correlates a decrease in metabolic demand or availability of nutrients
-The cell decreases size to ensure survival
-they have a diminished function but are still viable
-can rectify itself if the condition that signaled adaptation is rectified OR may progress to cell death in the case of progressive ischemic atrophy |
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Term
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Definition
Proteasome degradation of cytosolic proteins
Many cytosolic and nuclear proteins are degraded via the ubiquitin-proteasome pathway
-protien is first conjugated to ubquitin
-Protien is degraded by the proteasome
-Resulting peptide fragments are further degraded into AA's or can join with MHC-1 in the golgli aparatus for membrane presentation |
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Term
| Lysosomal digestion of Autosomes |
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Definition
controlled intracellular digestion of autophagic vacules containing fragments of organelles (ER, Mitochondria)
-Lysosomes can degrade both exogenous and endogenous proteins |
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Definition
| Common during fetal development and occurs to the uterus postpartum |
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Definition
| Pathologic can be local or generalized and have numerous causes |
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Definition
Occurs with diminishing workload
-skeletal muscle will undergo disuse atrophy with decreased demand
-cells will contain fewer myofibrils and mitochondria
-reduced amount of ER
-occurs first and most significantly in the slow twitch fibers
-reversible condition that will rectify with increased demand
-if demand is not reintroduced atrophy may progress to death
-loss of muscle which leads to increased osteoclastic activity |
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Definition
| Seen in association with destruction of pyramidal cells, somatic motor units, or axonal transection |
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Definition
| Deficient tissue perfusion can result in a decrease in cell size and thus allowing for decreased oxidative demands |
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Definition
A decrease in cell size decreases its metabolic demands and helps to ensure its survival
-Skeletal muscles cells will atrophy to allow the catabolism and use of contractile proteins to be used in gluconeogenesis |
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Definition
| state of ill health, malnutrition and wasting that may occur in chronic disease |
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| What is Tumor Necrosis Factor |
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Definition
It is synthesized and released during inflammatory responses can increase proteolysis by stimulating proteosomes to degrade proteins
-seen in muscle wasting that occurs in chronic inflammation |
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| There are many conditions which can lead to Brain Atrophy what are they? |
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Definition
Huntington's: genetic disease wherein a mutant protein is produced that decreases the viability of neurons
MS: An autoimmune disease in which T cells target oligodendrocytes for destruction
Alzheimer's: gross atrophy through brain
-initial signs involve memory loss
-HISTOLOGICALLY: insoluble protein aggregates called AMYLOID PLAQUE develop around the neurons in the ECM
-Neurofibrillary tangles are aggregates of proteins that form within the neuron
Pick's: Affects Frontal Lobe
-initial signs involve personality changes
-HISTOLOGICALLY: large protein aggregates termed Picks bodies from within the neuron which are different than neurofibrillary tangles (which is lacking in Pick's patients) |
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Term
| Stress related Proteolysis |
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Definition
Glucocorticoids can increase proteasome degradation of cytosolic proteins
Mechanisms: ACTH is released in response to stress and in response to CRH. This targets the adrenal cortex to release
-Adolsterone and Cortisol |
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Definition
| a mineralocorticoid, which targets kidneys to increase Na+ (& H2O) reabsorption and decrease K+ levels, increased BV and BP |
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Term
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Definition
A glucocorticoid, which has a primary effect (glucongenesis)
-Synthesized inside the cells of the Zona Fasiciculata from cholesterol which is needed for steroidogensis is retrieved from LDL. Once released 90-95% of cortisol is transported bound to protein carriers, only 5-10% of cortisol circulated freely
-made on demand & not stored within cell
-influences the metabolism of most body cells
-as unbound cortisol circulates through tissue it is available for uptake which releases more bound cortisol from the plasma protein carriers |
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| Effects of Cortisol on Target Cell |
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Definition
Unbound cortisol diffuses passively through
the cell membrane and binds to glucocorticoid receptors
-it is then transported to the cell necleus where it binds to steroid regulated genes
-Activation of genes alter the rate of transcription |
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| What are the Effects of Cortisol? |
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Definition
The overall effect of cortisol is to enhance the production of glucose and decrease and metabolic activity not associated with that process
At target cell cortisol moves from its carrier protein:
-cortisol alters the gene expression, transcription and translation in a host of tissues
-usually not evident for about 60-90 minutes |
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| Effect on Carbohydrate Metabolism |
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Definition
-Cortisol increases the # of enzymes necessary to convert AA's into glucose
-7 to 10 fold increase in the rate of hepatic gluconeogensis
-inhibits the effects of insulin which maintains or increases blood glucose levels
-decreases glycogenesis and glucose utilization by body cell
-depresses the oxidation of NADH to NAD+ |
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| Explain the effects of Protein Metabolism |
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Definition
Has a catabolic effect
Proteolytic enzyme break down proteins in tissues
-released proteins are available for gluconeogensis
-occurs in skeletal muscle
Inhibits protein synthesis is most body cells, except the hepatocytes which actually increase the synthesis and release of plasma proteins |
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Definition
Enhances the activation of cellular lipases, promoting the breakdown of lipids
Has the effect of decreasing peripheral adipose mass but maintaining/expanding abdominal adipose mass and fat around the head & neck "Moon Face" and "Buffalo Hump"
Abdominal stria can result from both the stretching of overlying skin and the break down of protein in the overlying skin |
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| What is the effect of Cortisol on Bone and the Immune System |
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Definition
Bone: catabolic effect resulting in the breakdown of calcified bone matrix
Immune: inhibits production and action of inflammatory cytokines |
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| What is the Inactivation of Cortisol? |
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Definition
| Body tissue contain 11-BHSD which converts cortisol to cortisone, an inactive metabolite of corisol. It is useful for its potent anti-inflammatory effects |
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Definition
Cushings: High Level of Cortisone
-Hyperglycemia as cortisol suppresses the action of insulin
-increases blood glucose levels
-H2O retention
-Moon Face & Buffalo Hump
-Loss of muscle protein
-Fat distribution around abdomen |
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Term
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Definition
Increase in the # of cells in tissue
-typically results in an increased mass of tissue or organ
-occurs in tissue where individual cells are capable or mitotic division
-Cytokines activate genes controlling proliferation |
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Term
| PHYSIOLOGICAL HYPERPLASIA |
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Definition
Hormonal: related to an increase of growth factors &/or up-regulation of growth factor receptors
-Uterine Cycle: Stratum Basalis gives rise to the stratum functialis
Compensatory: remaining cells &/or stem cells are stimulated to proliferate upon damage to a tissue
-Liver regeneration which can occur after a mild or severe injury or surgical partial hepatectomy |
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Term
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Definition
Can result in an abnormal increase in cells
can be related to an over stimulation of target cell by hormone or growth factor
-Keloid Formation: overgrowth of fibroblast in response to injury & inflammation
-Benign Prostatic Hyperplasia: a common non-malignant enlargement of the prostate gland |
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Term
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Definition
Abnormal Cell growth or development of cells resulting in a change in the size, shape and arrangement of a specific tissue
-may return to normal or be a precursor to cancer
-Cells that are similar to cancer cells grow in a tissue but have not yet acquired the ability to invade into tissue or metastasize |
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Term
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Definition
Condition in which the stratified squamous epithelium of the distal esophagus is replaced by metaplastic simple columnar
-Can be a result of chronic gastric reflux of the stomach contents up into the esophagus
-HCL & Pepsin damage the normal the normal epithelial lining of the esophagus
-chronic inflammation results in metaplasia |
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Term
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Definition
cause is unknown
Risk factors include:
Frequent intercourse at an age <16
Multiple sexual partners
Multiple pregnancies
STD, HPV and smoking
Pap smear findings demonstrate histological change from normal surface squamous (compact nuclei) to abnormal squamous cells |
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Term
| What happens in Mild and Severe Dysplasia? |
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Definition
Mild: squamous cells vary in size and have a small increase in the nuclear to cytoplasmic ration and have increased pigmentation (hyperchromatism)
Severe: there is a very high nuclear to cytoplasm ration and significant hyperchromatism. The full thickness of the epithelium contains abnormal cells |
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Term
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Definition
Abnormal replacement of cells of one type by cells of another type
-May result in the transformation of cells within a tissue into another type of cell
Typically occurs in response to chronic chemical or physical irriation, inflammation
-Begins primarily in undifferentiated stem cells
cells can be converted only to other types within the tissue and not cross over into different tissue types
-Pseudostratifed ciliated columnar epithelium lining the trachea & bronchi can be substituted with stratifed squamous |
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Term
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Definition
Esophagus: chronic gastric reflux may induce changes in epithelium from stratified squamous to simple columnar (Barrett's metaplasia)
Respiratory: Chronic irration can stimulate replacement of pseudostratified ciliated columnar epithelium with stratified squamous
-this results in loss of the goblet cells and this mucus secretion |
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Term
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Definition
Genetically programmed cell suicide
a normal cellular process that induces an orderly series of events that results in the death of the cell
rids the body of excess & damaged cells which include those that have developed abnormally, are worn down, or have genetic alteration
Occurs in embryogenesis & organogenesis
Nuclear dissolution without complete loss of membrane integrity
Activation of endogenous enzymes leads to autophagy
As the cell self-digests it breaks apart into membrane bound fragments that exhibit plasma memebrane ligands to which phagocytic receptors may attach this doesn't damage the surrounding cells or matrix or contribute to inflammation |
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Term
| Can cells undergo Apoptosis by other cells? |
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Definition
Yes.
Natural Killer cells & Tc cells can induce target cell apoptosis through the release of granzymes & perforin |
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Term
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Definition
Unregulated enzymatic digestion of the cell that is typically a response to disturbance of the extracellular environment
Results from the swelling & rupture of a cell
Initiates an inflammatory response
Always pathologic as intercellular enzymes are released during rupture damaging surrounding matrix & tissue |
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Term
| Compare Apoptosis with Necrosis |
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Definition
APOPTOSIS:
cell shrinks
intact plasma membrane
Celllar contents are released in budding apoptotic vesicles
non-inflammatory
A physiological means of eliminating cells
NECROSIS:
Cells swells
Plasma membrane is disrupted
cellular contents may leak from cell
Inflammatory
Results from pathologic trauma |
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Term
| What are the 5 types of Necrosis? |
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Definition
1. Liquefaction
2. Coagulation
3. Caseous
4. Fat
5. Gangrenous |
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Term
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Definition
Typically involves microbia infection & chemotatic accumulation of leukocytes
-activation & release of lytic enzymes liquifies the cell & matrix
-Complete digestion of dead cells leads to liqueification
-the focal tissue appears creamy yellow (pus) due to the presence of dead leukocytes |
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Term
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Definition
Associated with infraction
related to interruption of blood flow and coagulation which preserves the basic structure of the cell
-the coagulated cell may persist for days until removed by phagocytes
The intracellular acidosis resulting from hypoxia denatures structural and globular proteins thus proteolysis can't proceed so that the focal tissue remains its basic structure and exhibits a firm texture |
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Definition
Tissue architecture is obliterated as cells necrotic cells degenerate
The underigestion center of liquefaction takes on a cheese-like consistency and appearance
There remains a distinct border |
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Term
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Definition
Lipase enzymes liberate fatty acids from triglycerides
these fatty acids combine with ions such as Na+, Ca2+ and Mg2+ to form soaps and when it combines with Ca2+ it produces fat saponification
tissue demonstrates an opaque apperance
occurs in acute Pancreatitis where pancreatic lipase escapes and liquefies fat cell membranes |
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Definition
| Considerable amounts of necrotic tissue may become gangrenous. |
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| Define Gangrene and Name the 3 types of gangrene |
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Definition
Gangrene is a form of coagulative necrosis that typically results form hypoxia or ischemia
1. Dry Gangrene
2. Moist Gangrene
3. Gas Gangrene |
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Term
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Definition
Doesn't typically involve a bacterial infection or open wound
-tissues become deprived of oxygen and necrosis
-tissues appear dry & dark (brown/black)
-as tissues die they dry out & shrivel, may slough off
May be a result of Blunt trauma, Acute arterial obstruction, diabetes, frost bite, Atherosclerosis |
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Term
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Definition
Tissue appears moist, black & swollen
There is accompanying liquefaction necrosis due to the extensive lytic activity of enzymes released by the dying cells
At cell death intracellular enzymes dissolve cellular components & ECM which produce chemtatic signals that attract phagocytic WBC |
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Term
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Definition
Typically follows trauma to skeletal muscle and infection of site with Clostridium Perfringens causing extensive tissue damage and necrosis
Lesions become infiltrated with gas bubbles (predominately H2 the product of bacterial fermentation of skeletal muscle
Toxins cause massive necrosis of muscle fibers allowing spread of the bacterium |
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Term
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Definition
Neutrophils release cytokines such as:
-Leukotrienes: paracrines that coordinate local tissue responses to tissue injury
-Prostaglandins: increase local permeability |
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Term
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Definition
Inflammatory RXN lasting > 2 weeks
Can be related to:
-low grade inflammatory response that doesn't provide resolution
-unresolved infection
-Mycobacterium Tuberculsis
-Persistent chronic irritation with recurrent inflammation |
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