Cell Adaptation and Injury Mindmap: Brahma

Cell Adaptation and Injury Mindmap: Brahma

1. ATROPHY

   • -Decrease in cell size -Number of cells doesn't change Due to 1. Increased ubiquitin proteasomal degradation of proteins 2. Autophagy 3. Apoptosis
   • Disuse atrophy
     • -Decreased energy requirement -Cell structure changes: Muscles have less ER, mitochondria, filament
   • Denervation atrophy
     • -Nerve stimulation to muscle lost -Ex: Stroke patient
   • Lack of hormone stimulation
   • Inadequate nutrition
     • Protein energy malnutrition : Marasmus and Kwashiorker
   • Ischemia
     • -Decreased blood flow to organ -Leads to atrophy of cells and organ itself
   • senile atrophy

2. HYPERTROPHY

   • -Increase in cell size --> tissue --> organ -Occurs in cells that can't increase in numbers (Ex: cardiac and striated -Increased protein, myofilaments, mito
   • Physiologic
     • -Ex: athletes -proportional increase in width and length of muscle cell -Changes stimulated by stretch of muscle fibers -Promoted by biochemical signals (growth hormone and other ligands --> protein synthesis)
   • Pathophysiologic
     • -Ex: Concentric hypertrophy of heart in prolonged HTN, AS -Cells not proportional, malformed, not functioning properly -Change due to different signal molecules 

3. HYPERPLASIA

   • -Increase in number of cells in tissue/organ -Occurs in cells that can undergo mitosis -Mechanism: activation of genes controlling cell proliferation -Increased rate of cell division
   • Physiologyic
     • -Proliferation of breast parenchyma after puberty -
     • Compensatory hyperplasia
       • Regeneration of hepatocytes following partial hepatectomy
     • Hormonal hyperplasia
       • Endometrial hyperplasia due hyperestrogenic states--> Endometrial cancer Benign prostatic hyperplasia
   • Pathologic

4. METAPLASIA

   • -One cell type is replaced by another that is better able to survive -Mechanism: undifferentiated cells reprogrammed -Ex: In smokers, bronchial epithelial cells replaced by squamous cell 

5. DYSPLASIA

   • -Abnormal change in size, shape and organization of cells -Not a true adaptive change -Associated with irritation and inflammation
   • HPV Infection in cervix
     • HPV Infection I the cervix  Prolonged bronchus metaplasia

6. Stressors

   • Excessive use
   • Chemical exposure
   • Hypoxia
   • Physical Trauma
   • Infection and immune reactions
   • Genetic chagnes
   • Nutritional Imbalance

7. Cell Injury

   • -Cell membrane, unable to maintain homeostasis
   • Causes
     • IC Accumulation of substances
       • -Cell tries to dispose if they could -Accumulates in cytoplasm or organelles
       • Causes
         • Excessive
           • Too much normal body substance Ex: fat in liver (alcoholic cirrosis) Fatty liver pathophysiology: 1. Increased NADH halts TCA cycle and shunts citrate back to cytosol to fascilitate synthesis of FA. 2. Reduced packaging of FA into triglycerides in liver due to underexpression of apoB100 3. Increased activity of hormone sensitive lipase causes mobilization of free fatty acid from fat.
         • Abnormal endogenous substance
           • Abnormal lipids in brain (Tay Sachs disease)
         • Exogenous substance
           • From environment  Ex: Coal dust in miner lungs
       • Special stains used to identify IC accumulations
         • Oil red or Sudan black- Fat Prussian blue- Iron Congo red- Amyloid PAS- Glycogen Vonkossa- Calcium Masson Fontana- Melanin
     • Tissue calcification
       • Dystrophic
         • dead or dying tissues Ca salts deposited in injured tissues Ex: Atherosclerosis plaques (contains ca) Ex: Tuberculosis lesions, includes calcified granulomas
       • Metastatic
         • Hypercalcemia- deposits to normal tissues -Also leads to renal calculi (kidney stones) seen in hypercalcemic states
     • Physical agents
       • Damage cell structure 
       • Mechanical trauma
         • Direct damage to cells
       • Temp extremes
         • Damage to cells, organelle and enzymes -Hypothermia and frostbite
       • Electrical injury
         • damages tissues, disrupts cardiac and nerve impulses
       • Radiation
         • -Interrupt cell replication, cause mutation, kill cells -Cause cancers like leukemia 
     • Chemical exposure
       • Mechanisms: injure cell membranes, chemicals block enzyme pathways, coagulate proteins, toxic to cells (ex: liver cells) 
       • Drugs
         • Ex: Acetominophen toxic to liver
       • Lead
         • Interferes with nerve and brain development  -May be toxic to children
       • Mercury
         • Toxic to nerves and kidneys
     • Infections
       • Biologic agents invade and destroy cells -Viruses change cell DNA -Bacteria produce toxins -Microorganisms cause inflammatory/immune response
   • Mechanisms
     • -Lead to anaerobic metabolism, cell swelling and direct injury to cells 
     • Free Radicals
       • Molecules with unpaired electrons -Unstable/reactive -Damage cell membranes, DNA, tissues 
       • ROS
         • Reactive oxygen species -Oxygen-containing molecules that include free radicals -Produced by normal process (Ex: metabolic burst accompanying phagocytosis)
         • Oxidative stress
           • -Occurs when body unable to eliminate ROS -Plays role in aging and development of disease (Ex: cancer)
     • Hypoxic Cell Injury
       • Lack of oxygen, interrupts oxidative metabolism, generation of ATP -Heart, brain and kidneys cells damaged quickly 
       • Hypoxia
         • Lack of sufficient O2 to body cells, tissues and organs
         • Causes
           • -Blocked blood vessels -Respiratory disease, blocks inhalation and diffusion of oxygen across alveolar membrane 
           • Ischemia
           • Respiratory disease
           • Loss of hemoglobin
             • Carries oxygen to cells Leads to anemia 
           • Tissue edema
             • Can block oxygen from getting to cells
           • Inability to use oxygen
             • Ex: lactic acidosis -Cells unable to use oxygen even though it's being delivered to them
         • Results
           • Decreased ATP production, cells swell -Na/K pump fails -Na and water move into clls -Vacuoles form -Cytoplasm swells -Cells degenerate and rupture
           • Call membrane damange
             • -Cell destruction releases markers  >Troponin from damaged heart cells >AST/ALT from damaged liver cells 
       • Hypoxemia
         • Lack of O2 in the blood specifically 
       • Ischemia
         • Lack of enough oxygen to cells or organ -Leads to anaerobic metabolism -Ex: Myocardial eschemia- coronary arteries blocked 
         • Reperfusion Injury
           • -Occurs when O2 restored to ischemic tissue -Ischemia causes increase in ATP consumption, production of xanthine dehydrogenase -O2 --> metabolizes xanthine to produce massive amounts of superoxide hperoxide -Radicals cause membrane damage, ca overload of mitochondria -Mito pores open, ATP escapes, cells die 
           • Free Radicals
             • -Product of xanthine dehydrogenase metabolism from influx of O2 during reperfusion injury
       • Anoxia
         • Lack of oxygen to cells Ex: brain - cerebral anoxia 
     • Impaired Ca homeostasis
       • -Ca/Mg pump uses ATP to move Ca out of cell (only precise small amount needed in cell) -Cell membrane damage allows Ca to enter cell -Activates enzymes (proteases, lipases, protein kinases) that damage cell membranes, cytoskeleton, proteins, chromatin *-ases are enzymes that breakdown
   • Outcomes
     • Recovery
     • Apoptosis
       • -Programmed cell death -Purpose: removed injured cells -Cell fragments engulfed by phagocytes
       • Execution Pathways
         • carried out by proteolytic enzymes called caspases
         • Extrinsic Pathway
           • Activated by FAS ligand
         • Intrinsic Pathway
           • Usual pathway of apoptosis 1.Activated by signals like ROS 2. Withdrawl of hormonal stimulus
           • ROS
             • Activates intrinsic pathway, which signals apoptosis 
     • Cell Death
       • -Cell death to organ or tissue -Loss of cell membrane activity and enzyme breakdown of cell parts
       • Liquefaction necrosis
         • Enzymatic digestion by the degradative enzymes. E.g. Pus 2. Ischemia to brain
       • Coagulation necrosis
         • Ischemia to all tissues except Brain. Preservation of tissue architecture due to coagulation of proteins Preserved cell boundaries with loss of nuclei
       • Gangrene
         • Large area of necrosis 
         • Dry
           • Area shrinks, wrinkles -Turns black
         • Wet
           • dry gangrene when superadded bacterial infection commonly seen in diabetics
       • Caseous necrosis
         • Cottage cheese appearance due to mycolic acid of mycobacterium tuberculosis Granuloma in TB and fungal infections
       • Fibrinoid necrosis
         • Pink fibrin like material deposited in the media. Commonly seen in vasculitidis due immune complex deposition
         • Malignant HTN, PAN
   • Cell aging theories
     • -Molecular: Mutation or changes in gene expression -Cellular: senescence involving free radical injury, telomere shortening (happens with every cell division), apoptosis -Decline in integrative functions of organ systems  *Senescence- decline of functioning with age
     • Premature aging
       • Progeriasis due to the defect in nuclear lamins. An 8 year old boy looks like 80 year old physical appearance with skin wrinkles and cataract

8. Metaplasia

   • Change from one mature epithelium to another Reprogram by stem cells Eg. Smoking lead to aquamous metaplasia

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