Cell Adaptation and Injury Mindmap: Brahma

Annotations:

• -Decrease in cell size -Number of cells doesn't change Due to 1. Increased ubiquitin proteasomal degradation of proteins 2. Autophagy 3. Apoptosis

1. Disuse atrophy

   Annotations:

   • -Decreased energy requirement -Cell structure changes: Muscles have less ER, mitochondria, filament
2. Denervation atrophy

   Annotations:

   • -Nerve stimulation to muscle lost -Ex: Stroke patient
3. Lack of hormone stimulation
4. Inadequate nutrition

   Annotations:

   • Protein energy malnutrition : Marasmus and Kwashiorker
5. Ischemia

   Annotations:

   • -Decreased blood flow to organ -Leads to atrophy of cells and organ itself
6. senile atrophy

Annotations:

• -Increase in cell size --> tissue --> organ -Occurs in cells that can't increase in numbers (Ex: cardiac and striated -Increased protein, myofilaments, mito

1. Physiologic

   Annotations:

   • -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)
2. Pathophysiologic

   Annotations:

   • -Ex: Concentric hypertrophy of heart in prolonged HTN, AS -Cells not proportional, malformed, not functioning properly -Change due to different signal molecules 

Annotations:

• -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

1. Physiologyic

   Annotations:

   • -Proliferation of breast parenchyma after puberty -
   1. Compensatory hyperplasia

      Annotations:

      • Regeneration of hepatocytes following partial hepatectomy
   2. Hormonal hyperplasia

      Annotations:

      • Endometrial hyperplasia due hyperestrogenic states--> Endometrial cancer Benign prostatic hyperplasia
2. Pathologic

Annotations:

• -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 

Annotations:

• -Abnormal change in size, shape and organization of cells -Not a true adaptive change -Associated with irritation and inflammation

1. HPV Infection in cervix

   Annotations:

   • HPV Infection I the cervix  Prolonged bronchus metaplasia

1. Excessive use
2. Chemical exposure
3. Hypoxia
4. Physical Trauma
5. Infection and immune reactions
6. Genetic chagnes
7. Nutritional Imbalance

Annotations:

• -Cell membrane, unable to maintain homeostasis

1. Causes
   1. IC Accumulation of substances

      Annotations:

      • -Cell tries to dispose if they could -Accumulates in cytoplasm or organelles
      1. Causes
         1. Excessive

            Annotations:

            • 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.
         2. Abnormal endogenous substance

            Annotations:

            • Abnormal lipids in brain (Tay Sachs disease)
         3. Exogenous substance

            Annotations:

            • From environment  Ex: Coal dust in miner lungs
      2. Special stains used to identify IC accumulations

         Annotations:

         • Oil red or Sudan black- Fat Prussian blue- Iron Congo red- Amyloid PAS- Glycogen Vonkossa- Calcium Masson Fontana- Melanin
   2. Tissue calcification
      1. Dystrophic

         Annotations:

         • dead or dying tissues Ca salts deposited in injured tissues Ex: Atherosclerosis plaques (contains ca) Ex: Tuberculosis lesions, includes calcified granulomas
      2. Metastatic

         Annotations:

         • Hypercalcemia- deposits to normal tissues -Also leads to renal calculi (kidney stones) seen in hypercalcemic states
   3. Physical agents

      Annotations:

      • Damage cell structure 
      1. Mechanical trauma

         Annotations:

         • Direct damage to cells
      2. Temp extremes

         Annotations:

         • Damage to cells, organelle and enzymes -Hypothermia and frostbite
      3. Electrical injury

         Annotations:

         • damages tissues, disrupts cardiac and nerve impulses
      4. Radiation

         Annotations:

         • -Interrupt cell replication, cause mutation, kill cells -Cause cancers like leukemia 
   4. Chemical exposure

      Annotations:

      • Mechanisms: injure cell membranes, chemicals block enzyme pathways, coagulate proteins, toxic to cells (ex: liver cells) 
      1. Drugs

         Annotations:

         • Ex: Acetominophen toxic to liver
      2. Lead

         Annotations:

         • Interferes with nerve and brain development  -May be toxic to children
      3. Mercury

         Annotations:

         • Toxic to nerves and kidneys
   5. Infections

      Annotations:

      • Biologic agents invade and destroy cells -Viruses change cell DNA -Bacteria produce toxins -Microorganisms cause inflammatory/immune response
2. Mechanisms

   Annotations:

   • -Lead to anaerobic metabolism, cell swelling and direct injury to cells 
   1. Free Radicals

      Annotations:

      • Molecules with unpaired electrons -Unstable/reactive -Damage cell membranes, DNA, tissues 
      1. ROS

         Annotations:

         • Reactive oxygen species -Oxygen-containing molecules that include free radicals -Produced by normal process (Ex: metabolic burst accompanying phagocytosis)
         1. Oxidative stress

            Annotations:

            • -Occurs when body unable to eliminate ROS -Plays role in aging and development of disease (Ex: cancer)
   2. Hypoxic Cell Injury

      Annotations:

      • Lack of oxygen, interrupts oxidative metabolism, generation of ATP -Heart, brain and kidneys cells damaged quickly 
      1. Hypoxia

         Annotations:

         • Lack of sufficient O2 to body cells, tissues and organs
         1. Causes

            Annotations:

            • -Blocked blood vessels -Respiratory disease, blocks inhalation and diffusion of oxygen across alveolar membrane 
            1. Ischemia
            2. Respiratory disease
            3. Loss of hemoglobin

               Annotations:

               • Carries oxygen to cells Leads to anemia 
            4. Tissue edema

               Annotations:

               • Can block oxygen from getting to cells
            5. Inability to use oxygen

               Annotations:

               • Ex: lactic acidosis -Cells unable to use oxygen even though it's being delivered to them
         2. Results

            Annotations:

            • Decreased ATP production, cells swell -Na/K pump fails -Na and water move into clls -Vacuoles form -Cytoplasm swells -Cells degenerate and rupture
            1. Call membrane damange

               Annotations:

               • -Cell destruction releases markers  >Troponin from damaged heart cells >AST/ALT from damaged liver cells 
      2. Hypoxemia

         Annotations:

         • Lack of O2 in the blood specifically 
      3. Ischemia

         Annotations:

         • Lack of enough oxygen to cells or organ -Leads to anaerobic metabolism -Ex: Myocardial eschemia- coronary arteries blocked 
         1. Reperfusion Injury

            Annotations:

            • -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 
            1. Free Radicals

               Annotations:

               • -Product of xanthine dehydrogenase metabolism from influx of O2 during reperfusion injury
      4. Anoxia

         Annotations:

         • Lack of oxygen to cells Ex: brain - cerebral anoxia 
   3. Impaired Ca homeostasis

      Annotations:

      • -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
3. Outcomes
   1. Recovery
   2. Apoptosis

      Annotations:

      • -Programmed cell death -Purpose: removed injured cells -Cell fragments engulfed by phagocytes
      1. Execution Pathways

         Annotations:

         • carried out by proteolytic enzymes called caspases
         1. Extrinsic Pathway

            Annotations:

            • Activated by FAS ligand
         2. Intrinsic Pathway

            Annotations:

            • Usual pathway of apoptosis 1.Activated by signals like ROS 2. Withdrawl of hormonal stimulus
            1. ROS

               Annotations:

               • Activates intrinsic pathway, which signals apoptosis 
   3. Cell Death

      Annotations:

      • -Cell death to organ or tissue -Loss of cell membrane activity and enzyme breakdown of cell parts
      1. Liquefaction necrosis

         Annotations:

         • Enzymatic digestion by the degradative enzymes. E.g. Pus 2. Ischemia to brain
      2. Coagulation necrosis

         Annotations:

         • Ischemia to all tissues except Brain. Preservation of tissue architecture due to coagulation of proteins Preserved cell boundaries with loss of nuclei
      3. Gangrene

         Annotations:

         • Large area of necrosis 
         1. Dry

            Annotations:

            • Area shrinks, wrinkles -Turns black
         2. Wet

            Annotations:

            • dry gangrene when superadded bacterial infection commonly seen in diabetics
      4. Caseous necrosis

         Annotations:

         • Cottage cheese appearance due to mycolic acid of mycobacterium tuberculosis Granuloma in TB and fungal infections
      5. Fibrinoid necrosis

         Annotations:

         • Pink fibrin like material deposited in the media. Commonly seen in vasculitidis due immune complex deposition
         1. Malignant HTN, PAN
4. Cell aging theories

   Annotations:

   • -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
   1. Premature aging

      Annotations:

      • 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

Annotations:

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