Growth Adaptations, Cellular Injury, and Cell Death Flashcards
Hypertrophy - Mechanism
Gene activation, protein synthesis, production of organelles
Hyperplasia - Mechanism
Production of new cells from stem cells or resting cells
- Labile (stem) cells - Continuously divide
- Stable cells - Resting cells in Go phase of cell cycle that may be stimulated to enter cell cycle
Atrophy - Mechanism (2)
- Decrease in cell size
a. Increased catabolism of cell organelles and reduction of cytosol via autophagy in which autophagic vacuoles fuse with lysosomes
b. Increased catabolism of proteins by ubiquitin-proteasome pathway and decreased protein synthesis - Decrease in cell number by apoptosis
Metaplasia - Mechanism
Reprogramming of stem cells to utilize progeny cells with a different pattern of gene expression
Metaplasia - Barrett esophagus
Squamous epithelium –> Non-ciliated columnar epithelium with mucus-secreting cells and goblet cells
Metaplasia - Mainstem bronchus (smoking)
Pseudostratified columnar epithelium –> Squamous epithelium
Metaplasia - Schistosoma haematobium infection (urinary bladder)
Transitional (urogenital) epithelium –> Squamous epithelium
Metaplasia - Myositis ossificans
Mesenchymal tissue –> Bone
Metaplasia - Keratomalacia
Specialized epithelium (conjunctivae) –> Keratinizing, stratified squamous epithelium
(Vitamin A deficiency)
Dysplasia - Mechanism
Disorderly proliferation of cells
Dysplasia - Microscopic features (2)
- Increased mitotic activity with NORMAL mitotic spindles
2. Increased nuclear size and chromatin
Pathologic metaplasia without risk of progression to dysplasia and neoplasia?
Apocrine metaplasia of the breast (fibrocystic change)
Reversibility
- Metaplasia
- Dysplasia
- Neoplasia
- Metaplasia and dysplasia reversible
- Neoplasia irreversible
Hypoxia
Inadequate oxygenation of tissue
PaO2 - Contributing factors (4)
- Percent O2 in inspired air
- Atmospheric pressure
- Ventilation (PAO2 in the lungs)
- Perfusion and diffusion (Normal O2 exchange in the lungs through the alveolar-capillary membrane)
SaO2 - Contributing factors (5)
- Percent O2 in inspired air
- Atmospheric pressure
- Ventilation (PAO2 in the lungs)
- Perfusion and diffusion (Normal O2 exchange in the lungs through the alveolar-capillary membrane)
- Valence of heme iron in Hb
Fe2+ (ferrous, reduced) binds O2
Fe3+ (ferric, oxidized) does NOT bind O2
Hypoxia - Clinical findings (4)
- Cyanosis - Bluish discoloration of the skin and mucuous membranes (SaO2 < 80%)
- Confusion
- Cognitive impairment
- Lethargy
Oxidative phosphorylation (electron transport chain) - Cellular location
Inner mitochondrial membrane
Causes of tissue hypoxia (3)
- Ischemia
- Hypoxemia
- Decreased O2 carrying capacity
Ischemia - Definition
Decreased arterial blood flow to tissue or venous outflow from tissue
Hypoxemia - Definition
Decrease in PaO2 (PaO2 < 60 mm Hg, SaO2 < 90%)
Causes of hypoxemia (6)
- Decreased inspired PO2 (PiO2)
- Respiratory acidosis
- Ventilation defect
- Perfusion defect
- Diffusion defect
- Cyanotic congenital heart disease
Hypoxemia: Causes of decreased PiO2 (2)
- Breathing at high altitude
2. Breathing reduced %O2 mist
Hypoxemia: Respiratory acidosis - Definition
Retention of CO2 in the lungs
Increased PACO2 always produced decreased PAO2 (Dalton’s law - PO2 + PCO2 + PN2 = 760 mm Hg)
Hypoxemia: Ventilation defect - Definition
- Lung perfused but not ventilated
- Impaired O2 delivery to alveoli
Hypoxemia: Perfusion defect - Definition
Lung ventilated but not perfused
Hypoxemia: Diffusion defect - Definition
Decreased diffusion of O2 through the alveolar-capillary interface
Examples - Interstitial pulmonary fibrosis, pulmonary edema
Hypoxemia: Cyanotic congenital heart defect - Definition
Shunting of venous blood into arterial blood causes a drop in PaO2
Causes of decreased O2-carrying capacity (4)
- Anemia
- Methemoglobinemia (metHb)
- Carbon monoxide (CO) poisoning
- Factors causing a left-shifted Hb-O2 dissociation curve
Methemoglobinemia - Definition
Hb with oxidized Fe3+ (ferric iron) groups
Methemoglobinemia - Causes (3)
- Oxidant stress - Nitrite- or sulfur-containing drugs
- Congenital deficiency of cytochrome b5 reductase
- Decreased levels of cytochrome b5 reductase (newborns, until approx. 4 months of age)
Methemoglobinemia - Mechanism of hypoxia (2)
- metHb decreases the number of O2-binding sites, since O2 cannot bind Fe3+ in metHb
- metHb impairs O2 unloading (left-shifts Hb-O2 dissociation curve) by stabilizing R state
Methemoglobinemia - Pathognomonic clinical finding
Chocolate-colored blood (increased deoxy-Hb)
Methemoglobinemia - Treatment (2)
IV methylene blue, vitamin C
Cytochrome b5 reductase system
Cytochrome b5 reductase catalyzes the enzymatic reduction of metHb and the enzymatic oxidation of NADH
Fe3+ reduced to Fe2+
NADH oxidized to NAD+
NADPH-methemoglobin reductase system
NADPH-methemoglobin reductase catalyzes the enzymatic reduction of metHb and the enzymatic oxidation of NADPH
- Located in the pentose phosphate shunt
Fe3+ reduced to Fe2+
NADPH oxidized to NADP+
Methemoglobinemia - IV methylene blue (MOA)
Accelerates the enzymatic reduction of metHb by NADPH-methemoglobinemia reductase
- NOT normally operational in reducing metHb
Carbon monoxide poisoning - Mechanism of hypoxia (3)
- CO-Hb decreases the number of O2-binding sites, since binds Hb with 200x affinity versus O2
- CO-Hb impairs O2 unloading (left-shifts Hb-O2 dissociation curve) by stabilizing R state
- CO-Hb inhibits cytochrome oxidase in ETC, thereby preventing O2 consumption and ATP production
CO poisoning - Pathognomonic clinical finding
Cherry-red skin
CO poisoning - Early sign of exposure
Headache
CO poisoning - Treatment
100% O2 therapy
Factors causing a left-shifted Hb-O2 dissociation curve (6)
- metHb
- CO
- HbF
- Increased 2,3-BPG
- Decreased temperature
- Decreased H+ / increased pH / alkalosis