M1: Cellular Adaptation Flashcards
Type of Pathology that pertains to alterations in specialized organs and organ system
Specific
Study of structural changes that underlies disease. Uses molecular, microbiological, immunological and. Morphologic technique.
Pathology
Type of Pathology that pertains to basic reactions of cells and tissues to abnormal stimuli
General
Backbone in which diagnosis are made. Cause of the disease (genetic/acquired) A disease can be understood or a treatment plan to be developed.
Etiology
Etiology: due to bacteria, virus & parasites
Infectious
Etiology: due to deficiency or overproduction
Nutritional
Etiology: due to mutations or gene variants
Genetic
Etiology: due to UV rays
Chemical/Physical
Etiology: underlying causes such as multimutagenic factors and environmental factors (cance/atherosclerosis)
Multifactorial
Stars from initial to ultimate expression of disease. Sequence of events in response to etiological agent. A link between the specific molecular abnormalities to the specific clinical manifestations, to design new therepaeutic approaches.
Pathogenesis
Biochemical & Structural alterations in cells that are either characteristic or diagnostic of the etiological process
Molecular & Morphological Changes
Identify the nature and progression of disease by studying morphologic and chemical alterations but has limitations. Molecular, biological & immunologic process in analyzing disease states.
Diagnostic Pathology
Functional consequences. Progress of signs and symptoms and includes prognosis.
Functional Derangement and Clinical Manifestations
Father of Modern Pathology. All forms of disease start with a molecular or structural alterations in cells.
Rudolf Virchow
Normal cell with narrow range of structure and function caused by
Genetic program of Metabolism, Differentiation & Specialization “MDS”
Are more malignant than specialized cells
Undifferentiated cells
Altered physiologic state
Cellular Adaptation (reversible)
Reduced oxygen supply; chemical injury (ischemia) and microbiological infection.
Cellular injury & Cell death
Metabolic alterations. Can be genetic or acquired.
Intracellular accumulations & calcifications
Prolonged life span with cumulative sublethal injury but not enough to cause cell injury
Cellular aging
Cell injury can be reverted back to normal if the stimulus is
Removed
Chronic & Progressive stimuli. Downhill.
Irreversible Injury
Two types of Cell Injury
Fatty change & Cellular swelling “FC”
First manifestation. Hydrophobic degeneration.
Cellular swelling
Reversible changes in size, number, phenotype, metabolic activity or functions of cells. New but altered steady state are achieved fpr cell to survive or continue.
Cellular Adaptation
Examples of Reversible Injuries
Hypertrophy, Hyperplasia, Atrophy & Metaplasia “HHAM”
Increase in cell size & organ size. Occurs in both dividing & non-dividing cells. Can be physiologic or pathologic. Synthesis of more structural components of the cells. Caused by increased functional demand or by stimulation of hormones and growth factors.
Hypertrophy
Stimulus for Hypertrophy
Increased work load
Abnormal levels of hormones. Enlargement of thyroid gland (excess t3/t4, goiter) Increase functional demand. Chronic hemodynamic overload in left ventricular hypertrophy (hypertension & valvular disease)
Pathologic Hypertrophy
Hormonal increase in uterine size during pregnancy, breast and organs during puberty & breast during lactation. Functional demand increases like skeletal muscles during exercise.
Physiologic Hypertrophy
Hypertrophy results from increased production of
Cellular proteins
Hypertrophy is induced by
Growth factors, Vasoactive agents & Mechanical sensors “GVM”
Two biochemical pathways in Hypertrophy
Phosphoinositide 3-kinase/Akt pathway & Signaling downstream of G protein-coupled receptors “PS”
Among the two biochemical pathways of hypertrophy which one is pathologic
Signaling downstream of G protein-coupled receptors
Among the two biochemical pathways of hypertrophy which one is physiologic
Phosphoinositide 3-kinase/Akt pathway
Switch of this occurs during adult fetal transition
Contractile proteins
Some genes are expressed in _______ development and re-expressed in hypertrophic cells.
Early
It reaches a limit when enlargement of muscle mass can no longer compensate at regressive changes resulting to
Lysis & Loss of contractile elements
Dies by apoptosis or necrosis
Myocyte
Increase in number of cells & organ mass in cell population capable of dividing. A normal metabolic reaction.
Hyperplasia
Two types if Hyperplasia
Physiologic & Pathologic
A type of hyperplasia in which there is an increase in tissue mass after damage (after hepatectomy since liver is capable of regenerating)
Physiologic Compensatory Hyperplasia
Excess of hormones (endometrial atypical cancerous hyperplasia & benign prostatic hyperplasia due to the increase number of prostate gland) or growth factors (keloid from excessive collagen/skin deposition & papilloviruses such as warts in the skin)
Pathologic Hyperplasia
A type of hyperplasia in which there is an increase functional capacity of tissue when needed (breast when pregnant or puberty, uterus im pregnancy & proliferative endometrium)
Physiologic Hormonal Hyperplasia
Mechanism of Hyperplasia: Increase of _________.
Growth factor
Mechanism of Hyperplasia: Increase of growth factor _________.
Receptors
Mechanism of Hyperplasia: Activation of cellular __________.
Signalling pathways
Mechanism of Hyperplasia: Result of __________ driven proliferation of mature cells.
Growth-factor
Mechanism of Hyperplasia: Increased output of new cells from ____________.
Tissue stem cells
Reduced size of organ or tissue from decrease in cell size and number. Reduction of metabolic needs for cell survival. Fewer mitochondria, RER & cytoskeleton. Cells may have diminished function, but not yet dead.
Atrophy
Atrophied cells usually die by
Apoptosis
Type of Atrophy which is common during early development. Uterus after parturition.
Physiologic Atrophy
Due to diminished blood supply & irreversible injury. Inadequate nutrition, pressure & loss of endocrine stimulation.
Pathologic Atrophy
Pathologic atrophy due to decreased workload
Atrophy of disuse
Pathologic atrophy due to loss of innervation
Denervation atrophy
Atrophy is due from decreased ___________ (reduced metabolic activity) and increased ____________.
Protein synthesis. Protein degradation.
Mechanism of Atrophy: Pathway activated by nutrient deficiency and disuse. Cancer cachexia and responsible for accelerated proteolysis.
Ubiquitin-proteosome pathway
Mechanism of Atrophy: starved cells eat up its own components. Vacuoles fuse with lysosomes.
Increased Autophagy (Autophagic vacuoles)
Mechanism of Atrophy: Increased ___________. (Chronic renal disease with presence of scarring)
Residual bodies
Brown atrophy of the heart
Lipofuscin pigment
Reversible change from one differentiated cell type to another. May initiate malignant transformation in metaplastic epithelium. Reprogramming of stem cells or undifferentiated mesenchymal cells.
Metaplasia
Type of Metaplasia: Columnar to squamous (most common) & Squamous to columnar.
Epithelial Metaplasia
Epithelial Metaplasia examples are respiratory tract/ Vitamin A deficiency, Excretory ducts of glands-stones, Endocervix & chronic cervicitis.
Squamous to columnar
An example of Epithelial metaplasia that has a squamous to columnar transition in which if it persist may initiate malignant transformation
Barret Esophagus
Metaplasia is basically a result of
Stem cell reprogramming
Can undergo both hypertrophy & hyperplasia at the same time
Uterus during Pregnancy
Medical term for the specific symptom or landmark of a disease
Pathognomonic
Normal ventricular thickness
1.3-1.5cm
Occurs in both epithelial & mesenchymal tissues
Metaplasia
Type of Metaplasia from muscle to bone. Formation of cartilage, bone or adipose in places that do not contain these elements.
Connective tissue metaplasia
Example of a connective tissue metaplasia
Myositia Ossificans
Limits of adaptive responses are exceeded or cells are exposed to injurious agents, deprived of nutrients or by mutations. Suffers irreversible injury if stimulus persists or is severe.
Cell Injury
Causes of Cell Injury
Chemical agents & drugs, Oxygen deprivation, Physical agents, Infectious agents, Immunologic reactions, Nutritional imbalances & Genetic derangements “COPIING”
Reduced aerobic oxidative respiration due to Oxygen deprivation
Hypoxia
Hallmark of Reversible Injury
Depletion of ATP & Cellular swelling
In early stages or mild forms of injury. Reduced oxidative phosphorylation with depletion of ATP & cellular swelling. Mitochondria & Cytoskeletom have alterations.
Reversible Injury
With continuing damage. Irreversible. Necrosis & Apoptosis. End result of Autophagy.
Cell death
Digestion of cell. Mainly pathologic.
Necrosis
Cell kills itself
Apoptosis
Cellular swelling, fatty change, blebbing of plasma membrane, detachment of ribosomes from ER and clumping of nuclear chromatin.
Reversible Injury
During hypoxic injury there is appearance of liquid vacuoles (toxin & metabolic injury)
Fatty change
Cells are incapable of maintaining homeostasis. Failure of energy-dependent ion pumps.
Cellular swelling
Mechanism of Cell Injury: response depends on ________, _______ and _______ of injury.
Nature, Duration & Severity “NDS”
Mechanism of Cell Injury: Consequences depend on _______, _______ and ________ of the cell.
Type. State. Adaptability.
Mechanism of Cell Injury: Results from different __________ mechanisms acting on several essential cellular components.
Biomechanical
Mechanism of Cell Injury: May simultaneously trigger _____________ systems.
Multiple interconnected
Mechanism of Cell Injury: Associated with hypoxic & toxic injury. Reduced supply of oxygen and nutrients, mitochondrial damage & actions of some toxins.
Depletion of ATP
Depletion of ATP: If depletion of 5-10%, Na K ATPase _________(causing swellling), Increase in ________ glycolysis & Influx of ______.
Reduce. Anaerobic. Calcium.
Depletion of ATP: If depletion of 5-10%, Reduction of ________ synthesis, _______ protein response and Irreversible damage to _______ & ________ enzymes.
Protein. Unfolded. Mitochondrial & Lysosomal.
Increase in cytosolic Ca, ROS & O2 deprivation.
Mitochondrial Damage
Mitochondrial Damage: high conductance channel & loss of membrane potential (cyclophilin D)
Mitochondrial Permeability Transition Pore
Mitochondrial Damage: Activation of apoptotic pathways
Cytochrome C & Caspases
Opening of the mitochondrial permeability transition pore. Failuer to generate ATP. Activates phospholipases, proteases, endonucleases and ATPases. Induces apoptosis by activiating caspases and increasing mitochondrial permeability.
Influx of Intracellular Ca & Loss of Ca Homeostasis
Initiate autocatalytic reactions. Disruption of organelles. Mutations and loss of enzymatic activity.
Accumulation of Oxygen-Derived Free Radicals
Are produced normally but are degraded and removed by cellular defense systems. When this increases or when scavenging systems are ineffective, there would be an excess which leads to oxidative stress.
ROS
ROS are produced by
Neutrophils & Leukocytes
Molecular oxygen is reduced by transferring 4 electrons to H+ to generate 2 H20 Molecules.
Redox Reaction
Products of Redox Reaction
Superoxide anion, Hydrogen peroxide & Hydroxyl ions “SHH”
Redox Reaction: Absorption of radiant energy. _________ water to OH and H+.
Hydrolyze
Redox Reaction: __________ of ROS during Inflammation.
Rapid burst
Redox Reaction: __________ of exogenous chemicals or drugs.
Enzymatic metabolism
Redox Reaction: Transition metals like
Copper & Iron
Redox Reaction: As free radical or converted to ONOO
Nitric Oxide
Removal of Free Radicals: block formation or inactivate free radicals
Antioxidants (Vit. E & A)
Removal of Free Radicals: minimized by bonding to storage and transport proteins
Iron & Copper Bonding
Removal of Free Radicals: breakdown H202 and O2
Free radical scavenging systems
Free radical scavenging system: H202 to H2O +O2
Catalase
Free radical scavenging system: O2 to H2O2
Superoxide Dismutase
Free radical scavenging system: OH to H2O2 to H20 plus O2
Glutathione Peroxidise
Pathologic Effects of Free Radicals: Lipid _______ in membranes.
Peroxidation
Pathologic Effects of Free Radicals: _________ modification of proteins.
Oxidative
Pathologic Effects of Free Radicals: Lesions in ______.
DNA
Mechanisms of Membrane Damage: Results of ________ & ____ mediated activation of phospholipases also by toxins or agents.
ATP depletion & Calcium
Mechanisms of Membrane Damage: ROS through _________.
Lipid peroxidation
Mechanisms of Membrane Damage: Decreased phospholipid ________.
Synthesis
Mechanisms of Membrane Damage: Increased phospholipid _________. Accumulation of lipid breakdown products.
Breakdown
Mechanisms of Membrane Damage: _________ abnormalities.
Cytoskeletal
Consequences: opening of permeability transition pore
Mitochondrial damage
Consequences: Loss of osmotic balance and influx of fluid and ions
Plasma membrane damage
Consequences: Leakage of enzymes
Lysosomal membrane damage
Damage to DNA and proteins
Improper folding
End result of progressive cell injury. Irreversible. Caused by ischemia, infection and toxins. Normal and essential in embryogenesis. Two pathways would be necrosis and apoptosis. Autophagy and cells can no longer recover from injury.
Irreversible Injury/Cell Death
Due to nutrient deprivation
Autophagy
Spectrum of morphologic changes that follow cell death in living tissue due to denaturation of proteins and progressive enzymatic digestion. Unable to maintain integrity resulting to its contents leaking out and eliciting inflammation. Take hours to develop. Enzymes derived from lysosomes. Gross appearance depends on the appearance.
Necrosis/Cell Death
Microbiologic features of Necrosis: Increased eosinophilia due to loss of
Cytoplasmic RNA
Microbiologic features of Necrosis: More ______, homogenous appearance (loss of glycogen)
Glassy
Microbiologic features of Necrosis: presence of _______ figures. Become ________.
Myelin. Calcified.
Microbiologic features of Necrosis: Nuclear changes are noted like
Pyknosis, Karyorrhexis & Karyolysis “PKK”
Nuclear changes: fragmentation
Karyorrhexis
Nuclear changes: nuclear shrinkage and increased basophilia
Pyknosis
Nuclear changes: chromatin fades
Karyolysis
Most common except in the brain. Basic cellular outline preserved. Firm texture & Nuclear changes. Intracellular acidosis block proteolysis. Hypoxic death. Preserved architecture but cannot precipitate the cellular details, no nucleus. Localized area (infarct) wedge shaped.
Coagulative
Loss of blood supply. Has undergone coagulative necrosis. Mostly in the limbs.
Gangrenous
Focal bacteria or occasionally fungal infections. Hypoxia & CNS affectations. Complete digestion of dead cells and presence of pus. Transformation into liquid viscous mass. Accumulation of leukocytes. Wet gangrene. Initiated by Inflammation.
Liquefactive
Liquefactive necrosis usually occurs in the
Brain
Cheeselike, white appearance in area. Amorphous granular debris enclosed by granulomatous wall. Architecture completely obliterated. Granuloma. Foci of TB which may undergo non-caseation necrosis; hard or soft tubercle.
Caseous
Examples of Granulomas
Langhans fibrosis, Epitheloid cells & Lymphocytes “LEL”
Important in caseous cells/necrosis granulomatous walls which is activated by macrophages
Epitheloid cells
Multinucleated; horseshoe-shaped. Nucleus peripherally found.
Langhan’s type Giant Cell
Centrally located nucleus. Considered as haphazards.
Foreign Body Giant Cell
Focal area of fat destruction from release of pancreatic lipases. Visble chalky-white areas. Nonspecific pattern of cell death. Shadowing outlines. Lipase liquefy cell membranes-triglycerides-FFA+Ca-saponified fats. In acute pancreatitis.
Fat/Enzymatic
Breakdown fats to TG FFA then combines to calcium which is a process called sapofonication
Pancreatic lipases
Immune reaction involving blood vessels and vascular channels. Ag & Ab deposited in arterial walls. Renal problem like malignant nephrosclerosis. Chemical or toxic injury like cyanide, carbon tetrachloride and acetaminophen.
Fibrinoid
Most common type of cell injury. Restoration of blood flow exacerbates and accelerates cell injury. Additional cell loss. Hypoxia and Ischemia.
Ischemic and Hypoxic Injury
Reduced oxygen availability
Hypoxia
Reduced blood flow leading to a decreased supply of oxygen and nutrients which the cause more severe injury.
Ischemia
Example of Ischemic & hypoxic Injury
Anemia & CO poisoning
Mechanisms of Ischemic Cell Injury: oxygen ________ decrease. Then loss of ______. Results to decrease ______ generation.
Tension. OP. ATP.
Mechanisms of Ischemic Cell Injury: Failure of ________ (loss of K, influx of Na & H2O) and cell ________.
Na-K pump. Swelling.
Mechanisms of Ischemic Cell Injury: Influx of ____.
Calcium
Mechanisms of Ischemic Cell Injury: Loss of _______ and decrease _______ synthesis.
Glycogen. Protein.
Mechanisms of Ischemic Cell Injury: Presence of ________ figures.
Myelin
Mechanisms of Ischemic Cell Injury: Cytoskeleton disperses with loss of its structural features
Blebs
Mechanisms of Ischemic Cell Injury: ________ mitochondria and ______ ER.
Swollen. Dilated.
Mechanisms of Ischemic Cell Injury: May become irreversible. _______ of fatty acid residues.
Calcifications
Protective response promotes new BV formation, cell survival pathways and anaerobic glycolysis.
Hypoxia-inducible factor 1
Reperfusion after loss of blood supply may still pose danger. Reperfused tissues may sustain loss of cells in addition to the cells that are irreversibly damaged at the end of ischemia. Restoration of blood flow exacerbates and accelerates cell injury. E
Ischemia-Reperfusion Injury
Mechanisms of Ischemia-Reperfusion Injury: Increased generation of _____, _______ and ________ pathways.
ROS, RNS & Activation.
Mechanisms of Ischemia-Reperfusion Injury: Ischemia associated with inflammation and hypoxia due to
Cytokine production
Mechanisms of Ischemia-Reperfusion Injury: Activation of the
Complement system (IgM)
Injure cells directly by combining with critical molecular components. Most toxic chemicals must be converted to reactive toxic metabolites which act on target cells (CP450) examples are cyanide, CCL4 & Acetaminophen.
Chemical (Toxic Injury)
Programmed cell death. Induced by tightly regulated intracellular program. Chromatic condensation d/t nuclear changes. Formation of apoptotic bodies. Membrane remains intact. Structure alteration which leads to break up into apoptotic bodies. Does not elicit an inflammatory response. No nuclear changes.
Apoptosis
Tightly regulated suicide program in which cells are destined to die activate enzymes that degrade the cell’s own nuclear DNA and nuclear & cytoplasmic proteins.
Apoptosis
Physiologic/Pathologic Apoptosis: eliminate cells that are no longer needed to maintain the number of cell population
Physiologic
Physiologic/Pathologic Apoptosis: Embryogenesis- implantation, organogenesis, developmental involution and metamorphosis involution of hormone-dependent tissue upon hormone withdrawal.
Physiologic
Physiologic/Pathologic Apoptosis: Eliminate cells that are injured beyond repair
Pathologic
Physiologic/Pathologic Apoptosis: Involution of hormone-dependent tissues
Physiologic
Physiologic/Pathologic Apoptosis: DNA damage directly or via free radical production
Pathologic
Physiologic/Pathologic Apoptosis: Accumulation of misfolded protein (ER stress)
Pathologic
Physiologic/Pathologic Apoptosis: Elimination of harmful lymphocytes
Physiologic
Physiologic/Pathologic Apoptosis: Cell loss in proliferating cell populations
Physiologic
Physiologic/Pathologic Apoptosis: Elimination of harmful lymphocytes
Physiologic
Physiologic/Pathologic Apoptosis: Cell deaths in certain infections
Pathologic
Physiologic/Pathologic Apoptosis: Elimination of cells that are not needed anymore or in excess
Physiologic
Physiologic/Pathologic Apoptosis: Death of host cell
Physiologic
Physiologic/Pathologic Apoptosis: Atrophy in parenchymal organs
Pathologic
Morphologic Changes: cell shrinkage
Apoptosis
Morphologic Changes: cell swelling
Necrosis
Morphologic Changes: nuclear changes
Necrosis
Morphologic Changes: chromatin condensation (peripheral aggregates)
Apoptosis
Morphologic Changes: cytoplasmic blebs and apoptotic bodies
Apoptosis
Morphologic Changes: phagocytosis by macrophage
Apoptosis
Morphologic Changes: inflammation and engulfment of necrotic debris
Necrosis
Morphologic Changes: membrane blebs and destruction
Necrosis
Morphologic Changes: plasma membrane is intact until the last stages
Apoptosis
Biochemical Features: Activation of ________. Cysteine proteases. Must undergo enzymatic cleavage to become active.
Caspases
Biochemical Features: Initiator caspases
Caspases 8, 9 & 10
Biochemical Features: Executioner caspases
Caspases 3 & 6
Biochemical Features: DNA & Protein breakdown by _____ & _____ dependent endonucleases.
Ca2+ & Mg2+
Biochemical Features: Membrane alterations and recognition by ________. Movement of phosphatidylserine by _________.
Phagocytes. Annexin V.
Major mechanism. Result of increased mitochondrial permeability and release of pro-apoptotic molecules.
Intrinsic/Mitochondrial Pathway
Mitochondrial Pathway: initiates a suicide program
Cytochrome C
Mitochondrial Pathway: regulate apoptosis
BCl-2 proteins (Bcl-2, Bcl-x & Mcl-1)
Mitochondrial Pathway: allow proteins to leak out to the cytoplasm. Block Bcl-2 and Bcl-x.
Bax & Bak
Mitochondrial Pathway: Cytochrome C binds to Apag-1 to form _______ to bind to _______.
Apoptosome. Caspase 9.
Mitochondrial Pathway: block the activation of caspases
IAPs
Initiated by engagement of plasma membrane death receptors (TNF receptor family) Death Receptor Initiated Pathway.
Extrinsic Pathway
Extrinsic Pathway: delivery of apoptotic signals
Death domain
Extrinsic Pathway: example of death receptors
TNFR1 & FAS
Extrinsic Pathway: expressed on cytotoxic T cells
FasL
Extrinsic Pathway: form caspase 8 & 10
FADD
Extrinsic Pathway: form a binding site for FADD
3 Fas molecules
Extrinsic Pathway: inhibits apoptotic pathway but cannot cleave and activate caspase due to lack of protease domain
FLIP
Execution Phase: caspases involved. Cleaves a cytoplasmic DNAse inhibitor to make it active. Promote fragmentation.
3 & 6
Removal of Dead cells: is on the outer layer of the membrane
Phosphatidylserine
Removal of Dead cells: target dead cells for engulfment
Thrombospondin
Triggered by intrinsic pathway. Decrease synthesis of Bcl-2 and Bcl-x.
Growth factor deprivation
Arrests the cell cycle (G1 phase) Triggers apoptosis if damage is great. If absent it is incapable of apoptosis. DNA damage.
Gene p53
Due to ER stress
Protein misfolding
Activates NF-KB to promote cell survival
TNF
Promote entry of granzymes to activate caspases
Perforin
Secretes perforin. Medicated Apoptosis.
Cytotoxic T-Lymphocyte
Defective apoptosis and increase cell survival is due to
Mutation of p53
Increased apoptosis and excessive cell death results to
Neurodegenerative disease, Ischemic injury & Death of virus infected cells “NID”
Cell eats its own content. Intracellular organelles and cytosol portions are first sequestered to an autophagic vacuole and fuses to form a autophagolysosome to be digested by lysosomal enzymes.
Autophagy
Autophagy is regulated by
Atgs
Normal cellular constituent. Normally produced by cell but will synthesize in abnormal amounts. Abnormal substance can be endogenous or exogenous. Can be transient or permanent, harmless or toxic, intracytoplasmic or intranuclear and produced in cell or just stored in cell.
Intracellular accumulations
Four Abnormalities leading to intracellular accumulations
Lack of enzyme, Abnormal metabolism, Ingestion of indigestible materials and Defect in protein folding & transport “LAID”
Reversible. Fatty change. Abnormal accumulations of TGs within parenchymal cells. Seen in liver, heart, kidney & muscle. Causes are alcohol abuse, toxins, protein malnutrition, DM, obesity & anoxia. Excess accumulation results from excessive entry of defective metabolism and export of lipids.
Steatosis
Morphology of Steatosis: yellow, soft, greasy & tigered effect.
Macro
Morphology of Steatosis: clear vacuoles. (+) Sudan IV, (+) Oil Red O & fatty cyst.
Micro
Cholesterol & Cholesteryl Esters: smooth muscle cells and macrophage within the intima layer filled with lipid vacuoles.
Atherosclerosis
Cholesterol & Cholesteryl Esters: accumulation of cholesterol within macrophages
Xanthomas
Cholesterol & Cholesteryl Esters: focal accumulations in lamina propia of gallbladder
Cholesterolosis
Neimann-Pick disease & type C lysosomal storage disease
Cholesterol & Cholesteryl Esters
Normal Protein: reabsorption of droplets is proximal renal tubules
Proteinuria
Normal Protein: large, homogenous eosinophilic inclusions in the ER. Immunoglobulins.
Russel bodies
Rounded, eosinophilic droplets, vacuoles or aggregates in the cytoplasm.
Abnormal Protein
Abnormal Protein: defective intracellular transport and secretion of critical proteins.
ã1-antitrypsin deficiency
Abnormal Protein: accumulation of cytoskeletal proteins
Neurofibrillary tangles
Abnormal Protein: aggregation of abnormal proteins
Amyloidosis & Proteinopathies
Homogenous, glassy pink appearance on H&E stain. Example is ARDS.
Hyaline Change
Hyaline Change: extravasated plasma proteins and deposition of basement membrane material-collagenous tissue in old scar, hyalinated arterial walls, DM and long standing HPN.
Extracellular
Hyaline Change: Reabsorption of droplets, russel bodies and alcoholic hyaline.
Intracellular
Defect in synthesis of breakdown of glycogen; glycogen storage disease.
Glycogenoses
(+) Periodic Acid Shift & best Carmine
DM
Pigments: from outside of the body
Exogenous pigments
Pigments: Synthesized within the body. Do not evoke inflammatory response. Tattoo.
Endogenous pigment
Exogenous Pigments: associated with pneumoconiosis & anthracosis.
Carbon (coal dust)
Exogenous Pigments: deposition of black pigment in lungs
Anthracosis
Exogenous Pigments: coal miner disease
Pneumoconiosis
Endogenous Pigments: from the free radical damage and lipid peroxidation. Seen in aging, malnutrition & cancer. Micro yellow brown with perinuclear granules.
Lipofuscin
Endogenous Pigments: produced in melanocytes. Breakdown of tyrosine. Micro is black brown granules.
Melanin
Endogenous Pigments: alkaptonuria or ochronosis. Micro black granules.
Homogentisic acid
Endogenous Pigments: Hematin & Bilirubin. Hgb-derived. In liver, heart & endocrine organs. Hemosiderosis & Hemochromatosis. Micro gold brown granules and (+) Prussian blue.
Hemosiderin
Hematin is for
Malaria
Bilirubin is for
Jaundice
Abnormal tissue deposition of calcium and salts
Pathologic Calcification
Abnormal deposition of calcium salts in non-viable tissue. In areas of necrosis and occurs locally and in the absence of derangement in Ca2+ metabolism. Calcium levels not elevated.
Dystrophic Calcification
Dystrophic Calcification: Two process
Initiation & Propagation
Dystrophic Calcification: fine white granules
Macro
Dystrophic Calcification: Intracellular or extracellular basophilic granules. Psammoma bodies.
Micro
Dystrophic Calcification: medial calcifisclerosis. Calcification in Tunica Intima
Monckeberg’s
Abnormal deposition of Calcium salts in normal tissue in hypercalcemia. Found in interstitial tissue of gastric mucosa, kidney, lungs, arteries and pulmonary veins (internal alkaline compartments). Excretion of acid to have an internal alkaline compartment that predisposes them to this.
Metastatic Calcification
Causes of Metastatic Calcification: Increased PTH secretion
Hyperparathyroidism
Causes of Metastatic Calcification: destruction of _________.
Bone tissue
Causes of Metastatic Calcification: ________ related disorders.
Vit. D
Causes of Metastatic Calcification: ______ failure.
Renal
Result from progressive decline of cellular function and viability. Caused by genetic abnormalities and accumulation of cellular and molecular damage due to effects of exposure to exogenous influences.
Cellular Aging
Rare disease characterized by premature aging. Defective DNA helicase. Rapid accumulation of chromosomal damage.
Werner Syndrome
Most effective way of prolonging lifespan. Increase insulin activity and glucose metabolism.
Caloric restriction
Family of proteins with histone deactylase activity. Promote the expression of several genes whose products increase metabolic activity, reduce apoptosis, stimulate protein folding to and inhibit harmful effects of oxygen free radicals.
Sirtuins
Increase in cell size resulting in increased size of organs
Hypertrophy
Restoration of blood flow to ischemic but otherwise viable tissue paradoxically results in exacerbated and accelerated injury.
Ischemia-Reperfusion Injury
Refers to any abnormal accumulation of TAGs within parenchymal cells. Most often seen in the liver but can also occur in the heart, skeletal muscle and kidneys.
Steatosis
Most common cause of cell injury
Ischemia
Presence of cholesterol-filled macrophages in subepithelial connective tissue of skin or tendons
Xanthomas
Irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis
Pyknosis
