Patho-ch2 Flashcards
devoted to the study of the structural, chemical, and functional changes in cells, tissues, and organs that underlie disease
Pathology
concerned with the common reactions of cells and tissues to injurious stimuli
General pathology
Examines alterations and underlying mechanisms in organ specific diseases such as ischemic heart disease
Systemic pathology
Four aspects of a disease process: give their definition.
- Etiology- cause
- Pathogenesis- biochemical and molecular mechanisms of its development
- Morphologic changes- structural alterations induced in the cells and organs of the body
- Clinical manifestations - functional consequences of these changes
Two classes of etiology
Genetic - inherited
Acquired - e.g., infectious, nutritional, chemical, physical
Symptoms and signs of disease
Clinical manifestations
Clinical course and outcome of disease
Progress
Cell’steady state
Homeostasis
reversible functional and structural responses to changes in physiologic state
Adaptations
NIS: Altered physiologic stimuli; some nonlethal injurious stimuli
CR:?
Cellular adaptations
NIS: Increased demand, increased stimulation (e.g., by growth factors, hormones)
CR: ?
Hypertrophy/ hyperplasia
NIS: Decreased nutrients, decreased stimulation
CR: ?
Atrophy
NIS: Chronic irritation (physical or chemical), reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type
CR: ?
Metaplasia
NIS: Reduced oxygen supply; chemical injury; microbial infection
CR: ?
Cell injury
NIS: Acute and transient
CR: ?
Acute reversible injury, cellular swelling fatty change
NIS: Progressive and severe (including DNA damage)
CR: ?
Irreversible injury- cell death. Necrosis apoptosis
NIS: Metabolic alterations, genetic or acquired; chronic injury
CR: ?
Intracellular accumulations, calcification
NIS: Cumulative sublethal injury over long life span
CR: ?
Cellular aging
Nutrient deprivation triggers an adaptive cellular response called_______ and may also culminate in cell death.
Autophagy
This is stimulated by estrogenic hormones acting on smooth muscle through estrogen receptors, eventually resulting in increased synthesis of smooth muscle proteins and an increase in cell size.
Uterine hypertrophy
associated with increased atrial natriuretic factor gene expression
Cardiac hypertrophy
peptide hormone that causes salt secretion by the kidney, decreases blood volume and pressure, and therefore serves to reduce hemodynamic load.
Atrial natriuretic factor (ANF)
Occurs when there is a need to increase functional capacity of hormone sensitive organs; when there is need for compensatory increase after damage or resection
Physiologic hyperplasia
caused by excessive or inappropriate actions of hormones or growth factors acting on target cells.
Pathologic hyperplasia
Type of atrophy common during normal development
Physiologic atrophy
Type of atrophy, has several causes and it can be local or generalized
Pathologic atrophy
Enumerate the common causes of pathologic atrophy.
- Decreased workload (atrophy of disuse)
- Loss of innervation ( deneevation atrophy )
- Decreased blood supply
- Inadequate nutrition
- Loss of endocrine stimulation
- Pressure
AKA Profound protein-calorie malnutrition
Marasmus
brain and sometimes the heart may undergo progressive atrophy, mainly because of reduced blood supply as a result of atherosclerosis called_______
Senile atrophy
The most common epithelial metaplasia
Columnar to squamous
formation of cartilage, bone, or adipose tissue (mesenchymal tissues) in tissues that normally do not contain these elements
Connective tissue metaplasia
A direct link between transcription factor dysregulation and metaplasia is seen with _____________ deficiency or excess, both of which may cause metaplasia
vitamin A (retinoic acid)
Hallmarks of reversible injury
reduced oxidative phosphorylation with resultant depletion of energy stores (ATP), cellular swelling caused by changes in ion concentrations and water influx, intracellular organelles, such as mitochondria and the cytoskeleton, may show alterations.
a form of cell death that is characterized by nuclear dissolution, fragmentation of the cell without complete loss of membrane integrity, and rapid removal of the cellular debris AKA “programmed cell death”.
Apoptosis
“accidental” and unregulated form of cell death resulting from damage to cell membranes and loss of ion homeostasis
Necrosis
deficiency of oxygen, which causes cell injury by reducing aerobic oxidative respiration
Hypoxia
Enumerate the causes of cell injury
- Oxygen deprivation
- Physical agents
- Chemical agents and drugs
- infectious agents
- immunologic reactions
- genetic derangements
- nutritional imbalances
What are the two features of reversible injury recognized under light microscope?
Cellular swelling and fatty change
cells are incapable of maintaining ionic and fluid homeostasis, result of failure of energy-dependent ion pumps in the plasma membrane
Cellular swelling
Occurs in hypoxic injury and various forms of toxic or metabolic injury and manifested by the appearance of lipid vacuoles in the cytoplasm.
Fatty change
first manifestation of almost all forms of injury to cells
Cellular swelling
Ultrastructural changes of reversible injury
- Plasma membrane alterations
- mitochondrial changes
- dilation of ER
- nuclear alterations
form of necrosis in which the architecture of dead tissues is preserved for a span of at least some days; firm texture
Coagulative necrosis
localized area of coagulative necrosis
Infarct
characterized by digestion of the dead cells, resulting in transformation of the tissue into a liquid viscous mass
Liquefactive necrosis
A necrotic material that is frequently creamy yellow because of the presence of dead leukocytes
Pus
Not a specific pattern of cell death, usually involves lower leg that has lost its blood supply
Gangrenous necrosis
Superimposed bacterial infexn, more liquefactive because of the action of degradative enzymes and leukocytes
Wet gangrene
most often in foci of tuberculous infection; “cheeselike” and is derived from the friable white appearance of the area of necrosis
Caseous necrosis
Appearance of structureless collection of fragmented or lysed cells and amorphous granular debris enclosed within a distinctive inflammatory border; is characteristic of a focus of inflammation called_____
Granuloma
focal areas of fat destruction resulting from release of activated pancreatic lipases into the substance of the pancreas and peritoneal cavity called____________. Occurs in abdominal emergency known as________
Fat necrosis, Acute pancreatitis
Seen in immune reactions involving blood vessels, occurs when complexes of antigens and antibodies are deposited in the walls of arteries, these deposits together with fibrin result in a bright pink and amorphous appearance in H&E stains
Fibrinoid necrosis
Large whorled phospholipid masses that replaces dead cells
Myelin figures
Enumerate the 3 patterns of appearance during nuclear changes in necrosis. Describe each.
- Karyolysis- basophilia of chromatin fades, loss of DNA
- Pyknosis- nuclear shrinkage, increased basophilia, chromatin condenses
- Karyorrhexis- pyknotic nucleus undergoes fragmentation
Necrotic cells and cellular debris that are not destroyed or absorbed that allows deposition of calcium salts and minerals and calcified
Dystrophic calcification
Fundamental cause of necrotic cell death
Reduction/ Depletion of ATP
Enumerate: Cellular enzymes activated after increased cytosolic Ca2+ and their roles
- Phospholipases - causes membrane damage
- proteases - membrane and cytoskeletal protein damage
- endonuclease - nuclear damage (dna and chromatin fragmentation)
- ATPase - depetion of ATP
Chemical species that have a single unpaired electron in an outer orbit.
Free radicals
Type of oxygen derived free radical whose role is well established in cell injury.
Reactive oxygen species (ROS)
Increased production or decreased scavenging of ROS leading to increased free radicals is called _______
Oxidative stress
Enumerate ways of generetaion of free radicals
- reduction-oxidation process during normal metabolic processes
- absorption of radiant energy
- rapid bursts of ROS produced in activated leukocytes during inflammation
- enzymatic metabolism of exogeneous chemicals/ drugs
- transition metals
- nitric oxide
Enumerate the enzymes that act as free radical-scavenging systems
- Catalase
- Superoxidase dimutases
- glutathione peroxidase
Autocatalytic chain reactions
Propagation
Pathologic effects of ROS
- Lipid peroxidation inf membranes
- Oxidative modification of proteins
- Lesions in DNA
Biochemical mechanisms that may contribute to membrane damage
- Reactive oxygen species(lipid peroxidation)
- decreased phospholipid synthesis
- increased phospholipid breakdown
- cytoskeletal abnormalities
Most important sites of membrane damage
- mitochondrial membrane
- plasma membrane
- lysosomal membrane
Two phenomenas attributed to irreversible cell injury:
Mitochondrial dysfunction, membrane damage
Enumerate the mechanisms of cell injury
ATP depletion, mitochondrial damage, influx of calcium, increased permeability of cellular membrane, accumulation of reactive oxygen species (ROS), accumulation of damaged DNA and misfolded proteins
A protective response to deal with hypoxic stress, which promotes new blood vessel formation, stimulates cell survival pathways, and enhances anaerobic glycolysis.
Hypoxia-inducible factor-1
reperfused tissues may sustain loss of cells in addition to the cells that are irreversibly damaged at the end of ischemia.
Ischemia-reperfusion injury
Two general mechanisms that chemicals induce cell injury
Direct toxicity, conversion to toxic metabolites
Fragmented apoptotic cells is called_____
Apoptotic bodies
AKA “falling off”
Apoptosis
Genetically programmed necrosis by distinct type of genes
Necroptosis
Apoptosis in physiologic situations
- destruxn of cells during embryogenesis
- involution of hormone-dependent tissues upon hormone withdrawal
- cell loss in proliferating populations
- elimination of potentially harmful lymphocytes
- death of host cells that have served their usefull purpose
Pathologic apoptotic conditions
- DNA damage
- Accumulation of misfolded proteins
- cell death in certain infections
- pathologic atrophy in parenchymal organs after duct obstruxn
Morphologic and biochemical changes in apoptosis
- Cell shrinkage
- chromatin condensation
- formation of cytoplasmic blebs and apoptotic bodies
- phagocytosis of apoptotic cells / bodies by macrophages
Apoptosis results from activation of what enzymes
Caspases
Caspases become catalytically active
Initiation phase
Other caspases trigger the degradation of critical cellular components
Execution phase
Major mechanism of apoptosis in all mammalian cells
Intrinsic (mitochondrial) pathway
Anti-apoptotic proteins; posess _____ BH domains called_____
BCL2 , BCL-XL, MCL-1; 4; BH1-4
Apoptotic proteins; posses ___ BH domains
BAX and BAK; 4
Sensor proteins; posses _______ BH domain called______
BAD,BIM,BID,Puma,Noxa; 1; BH3-only proteins
Cytochrome C binds into a protein called______
APAF-1(Apostosis-activating factor-1)
Wheel-like hexamer
Apoptosome
initiated by engagement of plasma membrane death receptors on a variety of cells
Extrinsic (Death receptor-initiated) pathway
Cytoplasmic domain involed in protein-protein interactions
Death domain
Best known death receptor____; related protein_____
Type 1 TNF receptor (TNFR1); Fas (CD95)
cytoplasmic death domains form a binding site for an adaptor protein that also contains a death domain and is called_______
FADD (Fas-associated death domain)
Two initiating pathways converge to a cascade of caspase activation
Execution phase
Ligand that “flips out” for phagocytosis
Phosphatidylserine
Happens when unfolded or misfolded proteins accumulate in the ER because of inherited mutations or stresses triggering cellular responses
Unfolded protein response
Form of programmed cell death accompanied by the release of cytokine IL-1 with biochemical similarities to apoptosis
Pyroptosis
Process in which cell eats its own contents
Autophagy
Double-membrane bound vacuole
Autophagosome
Enumerate the three types of autophagy. Describe each
- chaperone-mediated autophagy - direct translocation of lysosomal membrane by chaperone proteins
- microautophagy - invagination of lysosomal membrane
- macroautophagy - sequestration and transportation of cytosol in an autophagosome
Autophagy-related genes are called______
Atgs
Failur to degrade a metabolite due to enzyme deficiencies
Storage diseases
Abnormal accumulation of triglycerides in parenchymal cells
Steatosis / fatty change
Clusters of foamy cells found in subepithelial connective tissue of the skin and in tendons producing tumor masses
xanthomas
smooth muscle cells and macrophages within the intimal layer of the aorta and large arteries are filled with lipid vacuoles, most of which are made up of cholesterol and cholesterol esters
Atherosclerosis
Focal accumultaions of cholesterol-laden macrophages foun din the lamina propria of gallbladder
Cholesterolosis
Lysosomal storage disease causing mutations in enzymes for cholesterol trafficking results in accumulations of cholesterol in multiple organs
Niemann-pick disease type C
ER distention producing Large homogeneous eosinophilic inclusions called_______
Russell bodies
Alterations within cells or extracellular space giving s homogeneous glassy pink appearance in histologic sections
Hyaline / hyaline change
Readily available energy source stored in the cytoplasm of healthy cells
Glycogen
Two kinds of pigments. Describe
Endogenous -produced in the body
Exogenous - from the outside of body
The most common exogenous pigment
Carbon
Blackening of tissues of the lungs and involved lymph nodes
Anthracosis
Serious lung disease caused by aggregates of carbon dust that may induce fibroblastic reaxn or emphysema
Coal worker’s pneumoconiosis
Form of localized exogenous pigmentation of the skin
Tattooing
An insoluble pigment; AKA _________ or _________
Lipofuscin; lipochrome, wear-and-tear pigment
Brown-black pigment formed when the enzyme tyrosinase catalyzes oxidation of tyrosine into dihydroxyphenylalanine
Melanin
One of major storage forms of iron
Hemosiderin
Localized hemosiderosis
Common bruise
Systemic overload of iron
Hemosiderosis
Increased absorption of dietary iron due to an inborn error of metabolism
Hemochromatosis
abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium, and other mineral salt
Pathologic calcification
result of a progressive decline in cellular function and viability caused by genetic abnormalities and the accumulation of cellular and molecular damage due to the effects of exposure to exogenous influences
Cellular aging
Cells become arrested in terminally nondividing state
Replicative senescence
Alterations within cells or extracellular space giving s homogeneous glassy pink appearance in histologic sections
Hyaline / hyaline change
