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157 Cards in this Set
- Front
- Back
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CELLULAR RESPONSES TO STRESS
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-CELLS ARE ACTIVE PARTICIPANTS IN THEIR ENVIRONMENT
-CONSTANTLY ADJUST STRUCTURE AND FUNCTION -ATTEMPT TO MAINTAIN HOMEOSTASIS -PRESERVE VIABILITY AND FUNCTION |
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FACTORS DETERMINING CELL INJURY
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Host Factors
Injury Factors |
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FACTORS DETERMINING CELL INJURY
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CELL TYPE:
-LABILE - CONSTANTLY REPLACED -STABLE - CAN BE REPLACED -PERMANENT - CAN’T BE REPLACED METABOLIC ACTIVITY DEFENSE MECHANISMS |
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FACTORS DETERMINING CELL INJURY
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TYPE
SEVERITY DURATION |
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BASIC MECHANISMS OF CELLULAR INJURY
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IMPAIRMENT OF AEROBIC RESPIRATION
IMPAIRMENT OF PROTEIN SYNTHESIS DISTURBANCES OF IONIC AND OSMOTIC BALANCE (CELL MEMBRANE) DEFECTS OF THE GENETIC APPARATUS |
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BASIC CAUSES OF INJURY
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-OXYGEN DEPRIVATION (HYPOXIA)
-PHYSICAL AGENTS -CHEMICAL AGENTS -BIOLOGIC AGENTS -IMMUNE DERANGEMENTS -GENETIC DERANGEMENTS -NUTRITIONAL IMBALANCES -AGING |
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CAUSES OF INJURY -OXYGEN DEPRIVATION-
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HYPOXIA
MOST COMMON CAUSE OF CELL INJURY/DEATH |
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OXYGEN DEPRIVATION EXAMPLES
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LOSS OF OXYGEN SUPPLY (DROWNING, PNEUMONIA)
LOSS OF BLOOD SUPPLY -DIMINISHED BLOOD FLOW (IMPAIRED ARTERIAL SUPPLY, REDUCED VENOUS DRAINAGE) -THROMBOSIS AND EMBOLISM LOSS OF BLOOD OXYGEN-CARRYING CAPACITY -CARBON MONOXIDE POISONING -BLOOD LOSS ANEMIA POISONING OF OXIDATIVE ENZYMES -CYANIDE |
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DROWNING
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3RD LEADING CAUSE OF UNINTENTIONAL INJURY DEATH:
-350,000 WORLDWIDE/YEAR -96% LOW-MIDDLE INCOME -2ND LEADING CAUSE OF DEATH IN CHILDREN UNDER AGE 12 IN U.S. |
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DROWNING STAGES
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1. WATER ENTERS AIRWAY
2. LARYNGOSPASM 3. CEREBRAL HYPOXIA (UNCONSCIOUSNESS) 4. WATER MAY ENTER LUNGS |
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THROMBOSIS
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FORMATION OF A CLOT IN A BLOOD VESSEL
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EMBOLISM
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MIGRATION OF A CLOT THROUGH VESSELS
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PULMONARY EMBOLISM
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-THROMBUS FORMS IN LOWER LEG VEIN
-THROMBUS COMES LOOSE AND EMBOLIZES -EMBOLUS LODGES IN PULMONARY ARTERIES -BLOOD FLOW THROUGH LUNGS CEASES -PATIENT DIES OF ANOXIA |
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HEMOGLOBIN + CO
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CARBOXYHEMOGLOBIN
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HEMOGLOBIN + O2
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OXYHEMOGLOBIN
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CARBON MONOXIDE POISONING
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56,133 DEATHS LAST YEAR
(FIRES, SUICIDES, UNINTENTIONAL) STOVES, HEATERS, CAR EXHAUSTS CO HAS 250X AFFINITY FOR HG THAN O2 100 ppm CO → 16% HgCO → DEATH HALF-LIFE = 3-4 HRS (30-90 MIN 100% O2; 15-25 MIN 100% HYPERBARIC O2 AT 2.5 ATM) |
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CYANIDE POISONING
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5,000-10,000 DEATHS/YEAR IN U.S. (SMOKE INHALATION, SUICIDES, HOMOCIDES)
INACTIVATES CYTOCHROME OXIDASE CELLULAR RESPIRATION CEASES METABOLIC ACIDOSIS ENSUES APNEA… DEATH 100% O2 AND CYANIDE ANTIDOTES |
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CAUSES OF INJURY -PHYSICAL AGENTS-
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MECHANICAL TRAUMA
TEMPERATURE EXTREMES CHEMICAL AGENTS ATMOSPHERIC PRESSURE CHANGE IRRADIATION ELECTRICAL SHOCK |
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DECOMPRESSION SICKNESS
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GAS BUBBLES FORMING INSIDE THE BODY UPON DECOMPRESSION
CAUSES (ASSENT FROM DEPTH - SCUBA DIVING; ASSENT TO ALTITUDE - UNPRESSURIZED AIRCRAFT; LEAVING HIGH PRESSURE ENVIRONMENT – MINES, SPACEWALKS) BREATH GASSES AT HIGH PRESSURE (GAS DISSOLVES INTO BODY FLUIDS; COMES OUT OF SOLUTION AS PRESSURE DECREASES) BUBBLES FORM IN JOINTS (“BENDS”), BLOOD, CSF… JOINT PAIN, PARALYSIS, “CHOKES”… |
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DECOMPRESSION SICKNESS TREATMENT
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PREVENT BY DECOMPRESSION STOPS
FIRST AID = 100% OXYGEN HYPERBARIC OXYGEN THERAPY |
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CAUSES OF INJURY -CHEMICAL AGENTS-
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DIRECT IRRITANTS
SYSTEMIC POISONS |
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CHEMICAL AGENTS
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-LARGE NUMBER OF SUBSTANCES
-EVEN GENERALLY INNOCUOUS SUBSTANCES (GLUCOSE, SALT, OXYGEN) -IMPROPER CONCENTRATIONS CAUSE INJURY -MANY ENCOUNTERED DAILY (ENVIRONMENTAL AIR POLLUTANTS; SOCIAL – e.g. ALCOHOL) -EVEN THERAPEUTIC DRUGS |
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CHEMICAL AGENTS MECHANISMS
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MEMBRANE PERMEABILITY
OSMOTIC HOMEOSTASIS ENZYME INTEGRITY |
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LEAD POISONING (PLUMBISM)
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-Pb HAS NO KNOWN PHYSIOLOGIC ROLE
-“SAFE” LEVEL = 10-25 ᶙg/dl -EXPOSURE: OCCUPATIONAL, PAINT, SOIL, WATER, PRODUCTS, HUNTING |
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LEAD POISONING (PLUMBISM) MECHANISM/SYMPTOMS
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NEPHROPATHY – TUBULAR MEMBRANE DAMAGE;
NEUROLOGIC – DEMYELINIZATION ANEMIA – DEFECTS IN HEME SYNTHESIS |
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LEAD POISONING (PLUMBISM) TREATMENT
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PREVENTION
CHELATION THERAPY |
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LEAD POISONING (PLUMBISM) PROGNOSIS
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WORSE IN CHILDREN
CNS EFFECTS IRREVERSIBLE |
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CAUSES OF INJURY -BIOLOGICAL AGENTS-
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BACTERIA
VIRUSES FUNGI PARASITES |
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IMMUNOLOGICAL REACTIONS
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IMMUNODEFICIENCIES (INHERITED OR ACQUIRED)
HYPERSENSITIVITIES AUTOIMMUNE REACTIONS REJECTION OF GRAFTED OR TRANSPLANTED TISSUE |
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GENETIC DEFECTS
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POINT MUTATIONS (50%; SICKLE CELL ANEMIA)
ANEUPLOIDY (25%; DOWN SYNDROME) ALTERATIONS IN CHROMOSOMAL MORPHOLOGY (25%; CHRONIC MYELOGENOUS LEUKEMIA) |
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NUTRITIONAL IMBALANCES
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DEFICIENCIES (PROTEIN-CALORIE DEFICIENCY; SPECIFIC VITAMINS)
EXCESSES (OBESITY; DIABETES) |
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CAUSES OF INJURY -AGING-
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MAXIMUM AGE =110 YEARS (↓ CELLULAR REPLICATION; ↓ REPAIR ABILITIES)
RANDOM EVENTS REDUCE LIFESPAN EARLY DISEASES OF OLD AGE REDUCE LIFESPAN LATE WOMEN OUTLIVE MEN BY 7 YRS (LIFESTYLE - SMOKING, ALCOHOL; VIOLENT DEATH; SUSCEPTIBILITY TO CERTAIN DISEASES-CARDIOVASCULAR DISEASE, CANCER) |
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MECHANISMS OF CELL INJURY -GENERAL PRINCIPLES-
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MOLECULAR BASIS OF DISEASE
COMPLEX, INTERWOVEN PROCESSES MANY PATHWAYS INVOLVED DIFFICULT TO PINPOINT SPECIFIC MOLECULAR ALTERATIONS CELLULAR RESPONSE DEPENDS ON TYPE, DURATION, SEVERITY OF INJURY CONSEQUENCES DEPEND ON TYPE, STATUS, ADAPTABILITY, AND GENETIC MAKE-UP OF CELL RESULTS FROM CHANGES IN: (MITOCHONDRIA – MOST IMPORTANT TARGET; CELL MEMBRANES; PROTEIN SYNTHESIS; CYTOSKELETON; GENETIC APPARATUS) |
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MECHANISMS OF CELL INJURY
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DEPLETION OF ATP
DAMAGE TO MITOCHONDRIA INFLUX OF CALCIUM OXIDATIVE STRESS DEFECTS IN MEMBRANE PERMEABILITY DAMAGE TO RNA AND PROTEINS |
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DEPLETION OF ATP CAUSES
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REDUCED OXYGEN SUPPLY
REDUCED NUTRIENT SUPPLY MITOCHONDRIAL DAMAGE SOME TOXINS (CYANIDE) |
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DEPLETION OF ATP SUSCEPTIBILITY
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GREATER GLYCOLYTIC ABILITY BEST (LIVER)
LESS GLYCOLYTIC ABILITY WORST (BRAIN) DEPLETION TO 5-10% OF NORMAL |
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DEPLETION OF ATP CONSEQUENCES
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SYNTHETIC/DEGRADATIVE PROCESSES CEASE
FAILURE OF SODIUM PUMP ↓ GLYCOGEN AND ↑ LACTIC ACID (pH changes) FAILURE OF CALCIUM PUMP STRUCTURAL DISRUPTION OF PROTEIN SYNTHESIS |
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DAMAGE TO MITOCHONDRIA CAUSES
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↑ CYTOSOLIC CALCIUM
OXYGEN DEPRIVATION TOXINS |
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DAMAGE TO MITOCHONDRIA CONSEQUENCES
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MITOCHONDRIAL PERMEABILITY TRANSITION PORE (LOSS OF MEMBRANE POTENTIAL; FAILURE OF OXIDATIVE PHOSPHORYLATION)
LEAKAGE OF CYTOCHROME c (INDUCTION OF APOPTOSIS) |
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INFLUX OF CALCIUM
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NORMALLY EXTRACELLULAR Ca++ >> CYTOSOLIC Ca++
LACK OF ATP → FAILURE OF Ca++ PUMP |
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INFLUX OF CALCIUM CONSEQUENCES
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ACTIVATION OF ENZYMES (PHOSPHOLIPASES, PROTEASES, ENDONUCLEASES)
INDUCTION OF APOPTOSIS |
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OXIDATIVE STRESS
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OXYGEN FREE RADICALS
SINGLE UNPAIRED ELECTRONS [HIGHLY UNSTABLE,REACTIVE OSYGEN SPECIES (ROS)] CAUSE MANY REACTIONS (REDOX REACTIONS; SUPEROXIDE RADICALS - H2O2; FENTON RXN WITH Cu AND Fe) |
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OXIDATIVE STRESS MECHANISMS OF ROS REMOVAL
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SPONTANEOUS DECAY
GLUTATHIONE PEROXIDASE FENTON RXN |
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OXIDATIVE STRESS EFFECT ON CELLS
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LIPID PEROXIDATION
PROTEIN CROSS LINKING DNA FRAGMENTATION |
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DEFECTS IN MEMBRANE PERMEABILITY -CAUSES-
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↓ PHOSPHOLIPID SYNTHESIS (DUE TO ↓ ATP PRODUCTION)
↑ PHOSPHOLIPID BREAKDOWN (PHOSPHOLIPASES) OXYGEN FREE RADICALS (LIPID PEROXIDATION) CYTOSKELETON ABNORMALITIES (↑ Ca++ → PROTEASES → DAMAGE) LIPID BREAKDOWN PRODUCTS (FREE FATTY ACIDS, DETERGENT EFFECT) |
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DEFECTS IN MEMBRANE PERMEABILITY -SITE OF DAMAGE-
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MITOCHONDRIAL MEMBRANES (↓ ATP PRODUCTION; PROTEINS TRIGGER APOPTOSIS)
PLASMA MEMBRANE (OSMOTIC IMBALANCE; INFLUX OF FLUID AND IONS; LOSS OF CELLULAR CONTENTS) LYSOSOMAL MEMBRANES (ENZYMES LEAK INTO CYTOPLASM; DIGESTION OF CELL COMPONENTS) |
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DAMAGE TO RNA AND PROTEINS
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DAMAGE TO DNA REPAIR MECHANISMS
IMPROPERLY INFOLDED PROTEINS BOTH TRIGGER APOPTOSIS |
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CELL INJURY AND NECROSIS -EXAMPLES-
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ISCHEMIA AND HYPOXIC INJURY
ISCHEMIA-REPERFUSION INJURY CHEMICAL (TOXIC) INJURY |
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ISCHEMIA
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IMPEDED ARTERIAL FLOW, OR
REDUCED VENOUS RETURN MOST COMMON INJURY IN MEDICINE |
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HYPOXIA
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OXYGEN DEFICIENCY
USUALLY ISCHEMIA BUT MANY OTHER CAUSES ↓ GENERATION OF ATP |
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ISCHEMIA AND HYPOXIA CONSEQUENCES
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LOSS OF FUNCTION
SUBCELLULAR CHANGES CLOUDY SWELLING REVERSIBLE IF OXYGEN IS RESTORED IN TIME IRREVERSIBLE IF PERSISTENT (NECROSIS, APOPTOSIS) |
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ISCHEMIA AND HYPOXIA
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FAILURE OF ENERGY-DEPENDENT SYSTEMS:
1. ION PUMPS – SODIUM, CALCIUM 2. DEPLETION OF GLYCOGEN STORES (LATIC ACID ACCUMULATES; pH CHANGES AFFECT CHEMICAL REACTIONS) 3. REDUCTION IN PROTEIN SYNTHESIS |
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ISCHEMIA-REPERFUSION INJURY
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RESTORATION OF BLOOD TO AREA OF ISCHEMIA
MAY RESULT IN EXACERBATED INJURY GENERATION OF ROS (INCOMPLETE REDUCTION OF O2 BY DAMAGED MITOCHONDRIA) INFLAMMATORY & IMMUNE REACTIONS (ACTIVATION OF COMPLEMENT; ANTIBODY DEPOSITION) |
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CHEMICAL (TOXIC) INJURY -DIRECT ACTION-
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COMBINE WITH CRITICAL MOLECULES/ORGANELLES (e.g. MERCURY POISONING: ATTACHES TO SULFHYDRAL GROUPS; INHIBITS ATP TRANSPORT; INCREASE MEMBRANE PERMEABILITY)
BASIS FOR CANCER CHEMOTHERAPY (TARGETS CELLS THAT USE, ABSORB, EXCRETE, OR CONCENTRATE CERTAIN CHEMICALS) |
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CHEMICAL (TOXIC) INJURY -INDIRECT ACTION-
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CHEMICAL NOT INTRINSICALLY HARMFUL
CONVERTED INTO TOXIC METABOLITE (BY P-450 OXIDASES) KILLS TARGET CELLS [FORMATION OF ROS; MEMBRANE DAMAGE; e.g. CARBON TETRACHLORIDE (CCl4)] |
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CARBON TETRACHLORIDE (CCl4) ACTION
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CHEMICAL (TOXIC) INJURY -INDIRECT ACTION-
CONVERTED TO CCl3 IN LIVER RAPID PHOSPHOLIPID PEROXIDATION (BREAKDOWN OF ER; ↓ PROTEIN SYNTHESIS; REDUCED LIPID EXPORT; “FATTY LIVER”) ALSO MITOCHONDRIAL DAMAGE (↓ATP STORES; DEFECTIVE ION TRANSPORT; Ca++ INFLUX; CELL DEATH) |
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STAGES OF CELL INJURY
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REVERSIBLE CELL INJURY
CELL DEATH |
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CELL INJURY OCCURS WHEN:
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STRESS IS SO SEVERE THEY CANNOT ADAPT
THEY ARE EXPOSED TO INHERENTLY DAMAGING AGENTS CELLS HAVE INTRINSIC ABNORMALITIES |
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REVERSIBLE CELL INJURY
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EARLY STAGES OF INJURY
MILD INJURY DAMAGING AGENT CAN BE REMOVED SIGNIFICANT STRUCTURAL & FUNCTIONAL CHANGES MAY OCCUR, BUT: CELL MEMBRANE INTACT; NUCLEUS NOT DISSOLVED |
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NECROSIS
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MAJOR CELL DEATH PATHWAY
ALWAYS PATHOLOGIC LYSOSOMAL ENZYMES DIGEST CELL RUPTURED PLASMA MEMBRANE ELICITS INFLAMMATION |
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APOPTOSIS
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CELLULAR SUICIDE
NUCLEAR DISSOLUTION MEMBRANE REMAINS INTACT ACTIVE, ENERGY-DEPENDENT PROCESS TIGHTLY REGULATED NOT ALWAYS PATHOLOGIC |
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CELL AND TISSUE INJURY -MORPHOLOGY-
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STARTS AT MOLECULAR LEVEL
CELL FUNCTION STOPS FIRST CELL DEATH LAGS BEHIND MORPHOLOGIC CHANGES ARE LAST TO OCCUR (e.g. MYOCARDIUM) [NONCONTRACTILE IN 1-2 MINUTES; DEAD IN 20-30 MINUTES; EM EVIDENCE IN 2-3 HRS; LIGHT MICROSCOPIC IN 6-12 HRS] |
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REVERSIBLE INJURY -LEVELS OF MORPHOLOGIC CHANGES-
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CELLULAR LEVEL (CELLULAR SWELLING; FATTY CHANGE)
SUBCELLULAR CHANGES EM CHANGES |
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REVERSIBLE CELL INJURY
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CLOUDY SWELLING
FATTY CHANGE STROMAL FATTY INFILTRATION HYALINE CHANGE MUCOID DEGENERATION FIBRINOID DEGENERATION |
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THE EARLIEST SIGN OF
CELL INJURY? |
CLOUDY SWELLING (HYDROPIC CHANGE)
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MECHANISM OF CLOUDY SWELLING
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INJURY -> MITOCHONDRIAL DAMAGE -> DECREASED ATP PRODUCTION -> FAILURE OF SODIUM PUMP -> INFLUX OF WATER
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CLOUDY SWELLING
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CELLULAR SWELLING OR HYDROPIC CHANGE
USUALLY FIRST SIGN OF INJURY WATER ACCUMULATES IN CELL ENTIRE ORGAN PALE & SWOLLEN ORGAN HEAVIER USUALLY NO EFFECT ON FUNCTION REVERSIBLE IF INJURY ABATES |
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CLOUDY SWELLING
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ULTRASTRUCTURAL:
EARLY (SWELLING OF MITOCHONDRIA; BLEBS IN PLASMA MEMBRANE) LATER (DISTENTION OF ER; DETACHMENT OF RIBOSOMES) CYTOPLASMIC: HYDROPIC SWELLING GROSS: SWOLLEN AND PALE |
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FATTY CHANGE
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STEATOSIS
MANY CAUSES (ALCOHOLISM, DIABETES, OBESITY) PARENCHYMAL CELLS (LIVER - ALCOHOLISM; HEART AND KIDNEY – HYPOXIA) CYTOPLASMIC: LIPID DROPLETS GROSS: YELLOW COLOR AND GREASY NO EFFECT ON FUNCTION IF MILD REVERSIBLE IF MILD |
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FATTY CHANGE MECHANISM
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TRIGLYCERIDE ACCUMULATION
INCREASED LIPID SYNTHESIS DECREASED LIPID UTILIZATION INCREASED LIPID TRANSPORT DECREASED LIPID MOBALIZATION |
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STROMAL FATTY INFILTRATION
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INGROWTH OF FAT INTO THE STROMA OF AN ORGAN
-NOT REALLY AN INJURY- |
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HYALINE CHANGE
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NON-SPECIFIC TERM FOR A SUBSTANCE WHICH IS: HOMOGENOUS, GLASSY, EOSINOPHILIC
INTRACELLULAR OR EXTRACELLULAR EXAMPLE: AMYLOID (FIBRILLAR WITH EM; STAINS WITH CONGO RED DYE; CHARACTERISTIC COMPOSITION) |
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SUBCELLULAR RESPONSES
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AUTOPHAGY
INDUCTION OF SER MITOCHONDRIAL ALTERATIONS CYTOSKELETON ABNORMALITIES |
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AUTOPHAGY
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“SELF-EATING”
LYSOSOMAL DIGESTION OF CELL COMPONENTS IN AUTOPHAGIC VACUOLE FUSED WITH LYSOSOME TO FORM AUTOPHAGOLYSOME DIGESTION OF COMPONENTS MAY TRIGGER APOPTOSIS UNDIGESTED MATERIAL IN RESIDUAL BODY |
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INDUCTION OF SER
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DUE TO EXPOSURE TO TOXINS
HYPERTROPHY OF SER MAY ACCOUNT FOR TOLERANCE MAKES DRUGS LESS EFFECTIVE MAKES SOME CHEMICALS MORE TOXIC |
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MITOCHONDRIAL ALTERATIONS
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INCREASED NUMBER (HYPERTROPHY)
DECREASED NUMBER (ATROPHY) ABNORMAL MORPHOLOGY (ALCOHOLICS) ALTERED FUNCTION (MITOCHONDRIAL MYOPATHIES) |
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CYTOSKELETON ABNORMALITIES
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REMODLEING OF INTRACELLULAR SCAFFOLDING
MAY CHANGE CELL MORPHOLOGY, SIZE, FUNCTION INHIBITION OF MOBILITY, CILIA |
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ULTRASTRUCTURAL CHANGES
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PLASMA MEMBRANE ALTERATIONS (BLEBS, DISTORTION OF MICROVILLI, LOOSENING OF CELLULAR ATTACHMENTS)
SWELLING OF MITOCHONDRIA DISTORTION OF ER DETACHMENT OF RIBOSOMES CLUMPING OF CHROMATIN |
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CELLULAR ADAPTATIONS
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REVERSIBLE CHANGES
RESPONSE TO ENVIRONMENTAL INJURY MAY BE PHYSIOLOGIC (HORMONES, EXOGENOUS CHEMICAL MEDIATORS) MAY BE PATHOLOGIC (CELLS MODULATE STRUCTURE/FUNCTION; ATTEMPT TO ESCAPE INJURY) |
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PATHOLOGIC CELLULAR ADAPTATION FORMS
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MAKE TAKE MANY DIFFERENT FORMS:
NUMBER OF CELLS SIZE OF CELLS PHENOTYPE OF CELLS METABOLIC ACTIVITY FUNCTION |
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CELL ADAPTATIONS
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ATROPHY
HYPERTROPHY HYPERPLASIA METAPLASIA DYSPLASIA |
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ATROPHY
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SHRINKAGE IN THE SIZE OF CELLS RESULTING IN SHRINKAGE IN THE SIZE OF AN ORGAN OR PART
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ATROPHY -GENERAL FEATURES-
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SHRINKAGE IN THE SIZE OF CELLS
RESULTS IN SHRINKAGE IN SIZE OF ORGAN OR PART SMALLER CELLS WITH DIMINISHED FUNCTION (NOT DEAD CELLS) CELL RETREATS TO A SIZE WHERE SURVIVAL IS POSSIBLE MAY BE PHYSIOLOGIC OR PATHOLOGIC |
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ATROPHY -CAUSES-
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DIMINISHED WORKLOAD (FUNCTIONAL DEMAND) [IMMOBILIZATION OF LIMB AFTER FRACTURE]
LOSS OF INNERVATION (PARAPLEGIC) DIMINISHED BLOOD SUPPLY (“SENILE ATROPHY” OF BRAIN) INADEQUATE NUTRITION (MARASMUS) LOSS OF ENDOCRINE STIMULATION (BREASTS AFTER MENOPAUSE) PERSISTENT CELL INJURY (CHRONIC INFLAMMATION) AGING (BRAIN) |
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UBIQUITIN-PROTEASOME PATHWAY
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ATROPHY MECHANISM
NUTRIENT DEFICIENCY ACTIVATES UBIQUITIN LIGASES UBIQUITIN ATTACHES TO CELLULAR PROTEINS PROTEINS DEGRADE IN PROTEASOMES |
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AUTOPHAGY
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ATROPHY MECHANISM
“SELF-EATING” FORMATION OF AUTOPHAGIC VACUOLES CELLS EATS ITS OWN COMPONENTS |
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HYPERTROPHY
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AN INCREASE IN SIZE OF INDIVIDUAL CELLS RESULTING IN AN INCREASE IN THE SIZE OF AN ORGAN OR PART
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HYPERTROPHY -GENERAL FEATURES-
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INCREASE IN SIZE OF CELLS
RESULTS IN AN INCREASE IN SIZE OF ORGAN OR PART NO NEW CELLS – JUST BIGGER CELLS INCREASED AMOUNTS OF STRUCTURAL PROTEINS AND ORGANELLES OCCURS IN CELLS INCAPABLE OF DIVIDING (PERMANENT TISSUES) MAY OCCUR ALONG WITH HYPERPLASIA |
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HYPERTROPHY -CAUSES-
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INCREASED FUNCTIONAL DEMAND: PHYSIOLOGIC (BODY BUILDER); PATHOLOGIC (HEART FAILURE)
INCREASED HORMONAL STIMULATION: PHYSIOLOGIC (UTERUS DURING PREGNANCY); PATHOLOGIC (GOITEROUS THYROID GLAND) |
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CARDIAC HYPERTROPHY
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INADEQUATE CARDIAC OUTPUT
MECHANICAL (STRETCH) AND TROPHIC (α-ADRENERGIC) STIMULATION SIGNAL TRANSDUCTION PATHWAYS ACTIVATED INDUCTION OF SEVERAL GENES SYNTHESIS OF CELLULAR PROTEINS (GROWTH FACTORS; STRUCTURAL PROTEINS - MYOFIBRILS) INCREASED CARDIAC PERFORMANCE BALANCE BETWEEN CARDIAC DEMAND AND FUNCTION IS ACHIEVED |
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LIMITATIONS ON HYPERTROPHY
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VASCULAR SUPPLY
MITCHONDRIAL ATP PRODUCTION COMPONENTS FOR STRUCTURAL PROTEIN FORMATION DECOMPENSATION CAN OCCUR (VENTRICULAR DILATION, CARDIAC FAILURE) |
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HYPERPLASIA
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AN INCREASE IN THE NUMBER OF CELLS RESULTING IN AN INCREASE IN THE SIZE OF AN ORGAN OR PART
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HYPERPLASIA -GENERAL FEATURES-
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INCREASE IN NUMBER OF CELLS
RESULTS IN AN INCREASE IN SIZE OF ORGAN OR PART MORE CELLS – NOT JUST BIGGER CELLS OCCURS IN CELLS CAPABLE OF REPLICATION MAY OCCUR ALONG WITH HYPERTROPHY CONTROLLED RESPONSE – DIFFERS FROM NEOPLASIA |
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PHYSIOLOGIC HYPERPLASIA -CAUSES-
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INCREASED FUNCTIONAL DEMAND (RBC’S AT ALTITUDE)
HORMONAL HYPERPLASIA (FEMALE BREAST AT PUBERTY AND DURING PREGNANCY; UTERINE EPITHELIUM AFTER MENSTRUAL PERIOD) COMPENSATORY HYPERPLASIA (REGENERATION OF LOST TISSUE; FOLLOWING RESECTION OR DISEASE EG REGENERATION OF LIVER; MEDIATED BY GROWTH FACTORS FROM RESIDUAL CELLS) |
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COMPENSATORY HYPERPLASIA
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REGENERATION OF LOST TISSUE
FOLLOWING RESECTION OR DISEASE (REGENERATION OF LIVER; MEDIATED BY GROWTH FACTORS FROM RESIDUAL CELLS) |
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PATHOLOGIC HYPERPLASIA -CAUSES-
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PERSISTENT INJURY (CALLOUS)
EXCESSIVE HORMONAL STIMULATION (IMBALANCE BETWEEN ESTROGEN AND PROGESTERONE; ENDOMETRIAL HYPERPLASIA; ABNORMAL UTERINE BLEEDING) EXCESSIVE GROWTH FACTOR PRODUCTION WOUND HEALING LEUKOCYTES SECRETE GROWTH FACTORS GROWTH FACTORS STIMULATE CT & BLOOD VESSEL PROLIFERATION “PROUD FLESH”… KELOID FORMATION VIRAL INFECTION HPV INFECTION OF SKIN EPITHELIUM VIRUS SECRETES GROWTH FACTORS EPITHELIUM PROLIFERATES TO FORM A WART |
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EXCESSIVE HORMONAL STIMULATION
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PATHOLOGIC HYPERPLASIA CAUSE
IMBALANCE BETWEEN ESTROGEN AND PROGESTERONE ENDOMETRIAL HYPERPLASIA ABNORMAL UTERINE BLEEDING |
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EXCESSIVE GROWTH FACTOR PRODUCTION
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PATHOLOGIC HYPERPLASIA CAUSE
WOUND HEALING (LEUKOCYTES SECRETE GROWTH FACTORS;GROWTH FACTORS STIMULATE CT & BLOOD VESSEL PROLIFERATION; “PROUD FLESH”… KELOID FORMATION) VIRAL INFECTION (HPV INFECTION OF SKIN EPITHELIUM; VIRUS SECRETES GROWTH FACTORS; EPITHELIUM PROLIFERATES TO FORM A WART) |
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METAPLASIA
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SUBSTITUTION OF ONE ADULT CELL TYPE FOR ANOTHER ADULT CELL TYPE
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METAPLASIA -GENERAL FEATURES-
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SUBSTITUTION OF ADULT CELLS TYPES
IN RESPONSE TO INJURY/STRESS SENSITIVE CELLS,RESISTANT CELLS FRAGILE CELLS, RUGGED CELLS EPITHELIAL OR MESENCHYMAL CELLS GENETIC REPROGRAMING OF STEM CELLS (CHANGE IN PHENOTYPE) REVERSIBLE IF STRESS IS REMOVED (CAN IMPAIR FUNCTION; CAN GIVE RISE TO NEOPLASIA!) |
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SQUAMOUS METAPLASIA OF BRONCHUS
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METAPLASIA -EXAMPLE
IN RESPONSE TO CIGARETTE SMOKING CILIATED PSEUDOSTRATIFIED COLUMNAR EPITHELIUM → SSE SSE MORE RESISTANT TO IRRITANTS LOSE OF CILIARY AND MUCUS PROTECTION MIGHT PREDISPOSE TO CANCER |
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SQUAMOUS METAPLASIA OF BLADDER
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METAPLASIA -EXAMPLE
PERSISTENT CYSTITIS |
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GASTRIC METAPLASIA OF ESOPHAGUS
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METAPLASIA -EXAMPLE
IN RESPONSE TO GASTRIC ACID REFLUX SSE BECOMES GASTRIC/INTESTINAL EPITHELIUM MUCUS PROTECTS MUCOSA BARRETT ESOPHAGUS PREDISPOSES TO ADENOCARCINOMA |
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OSSEOUS METAPLASIA OF COLLAGEN
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METAPLASIA EXAMPLE
INVOLVES MESENCHYMAL TISSUES CAUSED BY TRAUMA BONE FORMS WITHIN COLLAGEN TRAUMATIC MYOSITIS OSSIFICANS |
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METAPLASIA IN RESPONSE TO CHRONIC IRRITATION
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SQUAMOUS METAPLASIA IN BRONCHUS OF A SMOKER
GASTRIC METAPLASIA OF ESOPHAGUS 2 REFLUX SIGNIFICANCE: FULLY REVERSIBLE; CAN IMPAIR FUNCTION; MAY GIVE RISE TO NEOPLASIA |
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DYSPLASIA
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ALTERATION IN SIZE, SHAPE, AND ORGANIZATION OF THE CELLULAR COMPONENTS OF A TISSUE
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IRREVERSIBLE INJURY (DEATH) IS
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THE CESSATION OF SPONTANEOUS:
CEREBRAL FUNCTION RESPIRATION CIRCULATION |
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SIGNS OF SOMATIC DEATH
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ALGOR MORTIS - COOLING
LIVOR MORTIS - DISCOLORATION (DEPENDENT LIVIDITY) RIGOR MORTIS - STIFFENING |
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NON-PATHOLOGICAL CELL DEATH
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EMBRYOGENESIS
DEVELOPMENT OF ORGANS MAINTENANCE OF HOMEOSTASIS |
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IRREVERSIBLE CELL INJURY
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PAST NEBULOUS “POINT OF NO RETURN”
EVENTS ARE POORLY DEFINED TRANSITION IS POORLY UNDERSTOOD NO DEFINITE MORPHOLOGIC MARKERS NO DEFINITE BIOCHEMICAL MARKERS TYPICALLY INVOLVE EITHER: LACK OF OXIDATIVE PHOSPHORYLATION, OR DISTURBANCE OF MEMBRANE FUNCTION TYPES: NECROSIS AND APOPTOSIS |
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NECROSIS
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MORPHOLOGIC CHANGES IN TISSUE PRODUCED BY DEGRADATIVE ENZYMES FROM LYSOSOMES
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NECROSIS -GENERAL CHANGES-
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LACK OF MEMBRANE INTEGRITY
DUE TO ENZYMATIC ACTION (CELLULAR LYSOSOMES; FROM LEUKOCYTES IN INFLAMMATION) ENZYMES MAY BE DETECTABLE (IN BLOOD, SERUM, ETC; MAY BE OF DIAGNOSTIC USE; CREATINE KINASE/TROPONIN IN MI; TRANSAMINASES IN LIVER DISEASE) |
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NECROSIS -CYTOPLASMIC CHANGES-
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INCREASED EOSINOPHILIA
EARLY: GLASSY HOMOGENOUS APPEARANCE; LOSS OF GLYCOGEN PARTICLES LATER: VACUOLATION (ORGANELLE DIGESTION); FORMATION OF MYELIN FIGURES; SAPONIFICATION/CALCIFICATION |
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NECROSIS -NUCLEAR CHANGES-
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KARYOLYSIS (FADING OF CHROMATIN)
PYKNOSIS (SHRINKAGE AND BASOPHILIA) KARYORRHEXIS (FRAGMENTATION) NUCLEI DISAPPEAR IN 1-2 DAYS |
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TYPES OF NECROSIS
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AUTOLYSIS
HETEROLYSIS (APOPTOSIS, COAGULATIVE NECROSIS, LIQUEFACTIVE NECROSIS, SPECIAL TYPES) |
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AUTOLYSIS
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OCCURS AFTER SOMATIC DEATH
RAPID IN: GUT LINING, PANCREAS, ADRENALS |
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HETEROLYSIS
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OCCURS WHILE THE HOST IS ALIVE
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NECROSIS -MORPHOLOGIC PATTERNS-
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COAGULATIVE NECROSIS
LIQUEFACTIVE NECROSIS SPECIAL TYPES: CASEOUS NECROSIS, GUMMATOUS NECROSIS, GANGRENOUS NECROSIS, FAT NECROSIS (ENZYMATIC, TRAUMATIC), FIBRINOID NECROSIS |
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COAGULATIVE NECROSIS
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ISCHEMIC INJURY (↓ RNA/DNA SYNTHESIS, ↓ PROTEIN SYNTHESIS, RIBOSOMES DEGRANULATE)
BASIC CELL SHAPE AND TISSUE ARCHITECTURE PRESERVED NUCLEAR CHANGES OBVIOUS INCREASED EOSINOPHILIA (PROTEIN DENATURATION, LOSS OF RNA) |
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LIQUEFACTIVE NECROSIS
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TYPICAL OF BRAIN INFARCTION
ALSO SEEN IN ABSCESSES (PYOGENIC INFECTIONS) TISSUE DIGESTED TO LIQUID STATE |
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CASEOUS NECROSIS
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FORM OF COAGULATIVE NECROSIS
CASEATION (NECROSIS) CHESS-LIKE – YELLOW/WHITE AMORPHOUS GRANULAR DEBRIS TUBERCULOSIS TERMED A “GRANULOMA” IF FOCAL |
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GUMMATOUS NECROSIS
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FORM OF COAGULATIVE NECROSIS
RUBBERY MUMMIFIED TISSUE TERTIARY SYPHILIS |
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GANGRENOUS NECROSIS
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FORM OF COAGULATIVE NECROSIS
LOSS OF BLOOD SUPPLY TO LIMB OR ORGAN “DRY” GANGRENE (NOT INFECTED, MUMMIFIED TISSUE) “WET” GANGRENE (INFECTED, OOZES FLUID) |
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“WET” GANGRENE
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INFECTED
OOZES FLUID |
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“DRY” GANGRENE
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NOT INFECTED
MUMMIFIED TISSUE |
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ENZYMATIC FAT NECROSIS
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PANCREATITIS
LIPASES BREAK DOWN TRIGLYCERIDES COMPLEXES WITH Ca++ ->SOAPS OPAQUE AND CHALKY WHITE |
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TRAUMATIC FAT NECROSIS
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2° BLUNT TRAUMA
OCCURS IN BREAST NO SAPONIFICATION |
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FIBRINOID NECROSIS
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CAUSED BY IMMUNE REACTIONS
USUALLY INVOLVES BLOOD VESSELS ANTIGEN-ANTIBODY COMPLEXES IN ARTERY WALLS AMORPHOUS AND PINK POLYARTERITIS NODOSA |
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APOPTOSIS
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PROGRAMED CELL DEATH
PHYSIOLOGIC TURNOVER OF RENEWABLE CELLS IMMUNE REGULATION REGULATED CELL DEATH CELLULAR “SUICIDE” ELIMINATES: CELLS NO LONGER NEEDED, POTENTIALLY HARMFUL CELLS MAY COEXIST WITH NECROSIS NEOPLASTIC CELLS |
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APOPTOSIS -PHYSIOLOGIC CAUSES-
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CELLS DURING EMBRYOGENESIS
HORMONE-DEPENDENT TISSUE INVOLUTION LABILE CELL POPULATION MAINTENANCE ELMINATION OF: USED CELLS, SELF-REACTIVE LYMPHOCYTES INDUCED BY CYTOTOXIC T-LYMPHOCYTES (VIRALLY INFECTED CELLS, NEOPLASTIC CELLS) |
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APOPTOSIS -PATHOLOGIC CAUSES-
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CELLS WITH DAMAGED DNA
CELLS WITH ACCUMULATION OF MISFOLDED PROTEINS CERTAIN INFECTIONS E.g. VIRUSES ORGAN ATROPHY AFTER DUCTAL OBSTRUCTION |
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APOPTOSIS -BASIC MECHANISM-
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CAPASES ACTIVATED
DEGRADE NUCLEUS/CYTOPLASM PLASMA MEMBRANE INTACT CELLULAR FRAGMENTS PHAGOCYTIZED DOES NOT ELICIT INFLAMMATION CONTAINS DAMAGE |
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APOPTOSIS INTRINSIC PATHWAY
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MITOCHONDRIAL PATHWAY
CHANGE IN MITOCHONDRIAL PERMEABILITY RELEASE OF CYTOCHROME c ACTIVATION OF CAPASE 9 |
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APOPTOSIS EXTRINSIC PATHWAY
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DEATH RECEPTOR PATHWAY
SURFACE MOLECULES (TNF) ACTIVATE CAPASE 8 |
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APOPTOSIS -MORPHOLOGY-
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CELL ROUNDS UP AND SHRINKS
CELL STAINS EOSINOPHILIC CELL FRAGMENTS (APOPTOTIC BODIES) APOPTOTIC BODIES EXTRUDED PHAGOCYTOSIS OF BODIES |
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PATHOLOGIC CALCIFICATIONS
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DEPOSITION OF CALCIUM SALTS
MAY ALSO CONTAIN Fe, Mg… DYSTROPHIC CALCIFICATION OR METASTATIC CALCIFICATION |
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DYSTROPHIC CALCIFICATION
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OCCURS IN DEAD/INJURED TISSUE
SERUM CALCIUM LEVELS NORMAL GRITTY WHITE DEPOSITS (MAY AGGREGATE INTO LARGE MASSES) MAY BE SEEN ON RADIOGRAPHS (TUBERCULOSIS GRANULOMAS) BASOPHILIC ACELLULAR DEPOSITS MAY BE INCIDENTAL OR MAY COMPROMISE FUNCTION |
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DYSTROPHIC CALCIFICATION STEPS
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INITIATION (NUCLEATION)
PROPAGATION CRYSTALIZATION (CaPO4) |
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METASTATIC CALCIFICATION
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OCCURS WITH HYPERCALCEMIA
CAUSES: ↑ PTH, BONE DESTRUCTION, VITAMIN D-RELATED DISEASES, RENAL FAILURE USUALLY IN INTERSTITIAL TISSUES BLOOD VESSELS, KIDNEY, LUNG USUALLY NO CLINICAL DYSFUNCTION MASSIVE DEPOSITE SYMPTOMATIC (REMARKABLE RADIOGRAPHS, NEPHROCALCINOSIS) |
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INTRACELLULAR ACCUMULATIONS
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HARMLESS OR HARMFUL
IN CYTOPLASM, ORGANELLES, OR NUCLEUS SYNTHESIZED BY AFFECTED CELLS OR ELSEWHERE GENETIC OR ACQUIRED METABOLIC ACCUMULATIONS AND PIGMENTATIONS |
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INTRACELLULAR ACCUMULATIONS -MECHANISMS-
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INCREASED SYNTHESIS
EXCESSIVE UPTAKE UNDER UTILIZATION UNDER MOBALIZATION |
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METABOLIC ACCUMULATIONS
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LIPIDS (OBESITY, FATTY CHANGE)
CHOLESTEROL (MACROPHAGES BECOME “FOAM CELLS”, ATHEROSCLEROTIC PLAQUES) PROTEINS (NEPHROTIC SYNDROME, RUSSELL BODIES, MALLORY BODIES, NEUROFIBRILLARY TANGLES) GLYCOGEN (DIABETICS, GLYCOGEN STORAGE DISEASES) MUCOPOLYSACCHARIDES (STORAGE DISEASES) |
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INTRACELLULAR PIGMENTS -ENDOGENOUS-
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LIPOFUSCIN: WORN OUT ORGANELLES; “WEAR-AND-TEAR” PIGMENT; GOLDEN-BROWN COLOR; HEART, LIVER; ELDERLY INDIVIDUALS; “BROWN ATROPHY” OF ORGANS
MELANIN: FROM MELANOCYTES; EPHELIS, NEVUS, MELANOMA IRON: FROM ERYTHROCYTES; GOLDEN-YELLOW IN COLOR; HEMOSIDERIN (APOFERRITIN-Fe) – ECCHYMOSIS; HEMOSIDEROSIS; HEMOCHROMATOSIS BILIRUBIN COPPER |
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LIPOFUSCIN
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ATROPHIC ORGANS OF ELDERLY (“BROWN ATROPHY”)
HEPATOCYTES, MYOCARDIUM, NEURONS “WEAR AND TEAR” PIGMENT LIPID PEROXIDATION OF ORGANELLES GOLDEN-BROWN GRANULES IN LYSOSOMES NO HARM TO CELL |
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MELANIN
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BLACK-BROWN PIGMENT
DERIVED FROM TYROSINE EPIDERMAL CELLS OF SKIN UV LIGHT PROTECTION PRODUCED IN SOME TUMORS (NEVI, MELANOMAS) |
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IRON PIGMENTS
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FERRITIN AND HEMOSIDERIN
PRUSSIAN BLUE REACTION JAUNDICE, HEMOSIDEROSIS, HEMOCHROMATOSIS DEPOSITS IN LIVER, SKIN, SCLERA |
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BILIRUBIN
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YELLOW PIGMENT
RESPONSIBLE FOR JAUNDICE |
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COPPER
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WILSON’S DISEASE
LIVER - LIVER FAILURE BRAIN - ENCEPHALOPATHY EYES - KAYSER-FLEISCHER RING |
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PIGMENTATIONS -EXOGENOUS-
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ANTHRACOSIS
TATTOOS AMALGAM TATTOO |
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ANTHRACOSIS
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CARBON PARTICLES
IN CYTOPLASM OF MACROPHAGES LUNG, REGIONAL LYMPH NODES URBAN DWELLERS BURNING OF FOSSIL FUELS INDIGESTIBLE AND PERMANENT USUALLY DOES NOT HARM LUNGS (BLACK LUNG DISEASE) |
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CELLULAR AGING
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DNA DAMAGE
DECREASED CELLULAR REPLICATION REDUCED REGENERATIVE CAPACITY ACCUMULATION OF METABOLIC DAMAGE HORMONAL PATHWAYS |
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CELLULAR AGING -DNA DAMAGE-
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OCCURS DURING NORMAL REPLICATION
ENHANCED BY FREE RADICALS DEFECTS IN DNA REPAIR ↓ CALORIE INTAKE PROLONGS LIFE! (STRESS ACTIVATES SIRUTIN PROTEINS; CAUSES DEACETYLATION OF HISTONES; ACTIVATES DNA REPAIR ENZYMES; STABLILIZES DNA) |
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CELLULAR AGING -DECREASED CELLULAR REPLICATION-
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CELLS HAVE FINITE # OF DIVISIONS
REPLICATIVE SENESCENCE OCCURS PROGERIA AND WERNER SYNDROME (PREMATURE AGING; REDUCED CELL LIFE SPAN; DEATH BY AGE 50) PROGRESSIVE SHORTENING OF TELOMERES (NO TELOMERASE IN SOMATIC CELLS; TELOMERASE ACTIVE IN CANCER CELLS) |
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CELLULAR AGING -REDUCED REGENERATIVE CAPACITY-
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P16 PROTEIN IN STEM CELLS
LOSS OF CAPACITY TO SELF-RENEW |
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CELLULAR AGING -ACCUMULATION OF METABOLIC DAMAGE-
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ROS (MODIFIED PROTEINS, LIPIDS, NUCLEIC ACIDS)
PROTEASOME INACTIVITY (ALLOWS DAMAGED ORGANELLES TO ACCUMULATE) |
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CELLULAR AGING -HORMONAL PATHWAYS-
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INSULIN-LIKE GROWTH FACTOR
INTRACELLULAR SIGNALING PATHWAYS |
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EARLY SIGNS OF DEATH
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LACK OF MOVEMENT
CESSATION OF RESPIRATION CESSATION OF CIRCULATION PALLOR OF SKIN MUSCLE FLACCIDITY CONTACT FLATTENING EYE CHANGES |
