Intracellular accumulations

Intracellular accumulation of Lipids: Foamy cells/cholesterol deposits

• xanthomas: foamy cell accum in sub-epithelial connective tissue of. skin/tendon 

• foamy cells/streaks (cholesterol laden microphages0

  • atherosclerosis 

  • cholesterosis (gallbladder)

• Lysosomal storage diseases

  • group of inherited genetic disorders that affect the body’s lysozomes 

    • Neimann-pick disease type c 

      • autosomal recessive 

      • mutation in an enzyme involved in cholesterol trafficking (many organs: brain, liver, spleen)

• Fatty liver (abnormal metabolism)

Intracellular accumulation of Proteins: proteinuria

• reabsorption of protein droplets in renal tubules

  • elevated protein level in urine

  • symptom of other disease/condition

• not a disorder but happens when you have a specific disease 

Intracellular accumulation of Proteins: Alpha-1 Antitrypsin deficiency 

• A1A (produced in liver) usually coats lungs, protecting them from neutrophil elastase (produced by WBCs, used to destroy harmful bacteria)

• Lack of A1A leaves lungs susceptible to damage from enzyme (often mimics COPD) 

• also begins to build up in liver (causing damage) neurofibrillary tangles found in alzheimers 

Intracellular accumulation of Glycogen/carbon

• glycogen: energy source stored int he cytoplasm of healthy cells 

• excessive deposits when patients have abnormality in either glucose or glycogen metabolism 

  • diabetes mellitus

  • glycogen storage disorder

Intracellular accumulation of Pigments: Exogenous

• exogenous: originated from outside the body 

• carbon

  • inhaled carbon: anthracosis, coal miners pneumonconiosis

  • tattoos

Intracellular accumulation of Pigments: Endogenous

• endogeneous: originated from inside the body

• lipofuscin: free radical injuries, lipid perioxidation, and normal aging causes build-up in liver and heart

  • pigment that builds up in the skin, or deposited inside organs start to build up when you age (especially in highly vascular areas)

• melanin

• homosiderin: hemoglobin derived from iron

  • normal bruising, or systemic overload (yellow/brown pigment)

  • ion containing pigment inside RBC, spills out when there is cell damage and as it gets broken down its inner components turn into different colors (bruise)

• bilirubin: not breaking down blood cells which is a by product from something else

Bruising pathway 

Manifestations of cellular injury

• cellular accumulations (endogenous infiltrations)

  • urate/uric acid

  • calcium

• this can occur from protein breakdown, muscle damage, excess protein

• can be metabolic or from an injury

• contributes to gout (accumulation of uric acid crystals in joint) and can aggravate arthritis, UTI, kidney stones

Intracellular accumulation of Calcium: Pathologic calcification 

• abnormal tissue deposition of calcium salts plus iron, magnesium, and other mineral salts 

Intracellular accumulation of Calcium: Dystrophic calcification 

• occurs locally in dying tissue (more localized than metastatic calcification

• serum levels of Ca are normal 

  • causes fine white granular clumps 

Intracellular accumulation of Calcium: Metastatic calcification

• deposits of Ca salts in otherwise normal tissue 

• results from hypercalcemia (too much Ca in blood)

  • secondary to some disturbance in Ca metabolism 

    • increased secretion of PTH

    • resorption of bone tissue (from tumors of bone marrow: multiple myeloma, leukemia, etc.)

    • vitamin D related disorders (sarcoidosis, williams syndrome)

    • renal failure

  • serum calcium levels are elevated

  • pull minerals from bone, tells digestive tract to absorb more Ca from food so Ca concentration in blood will be through the roof

calcium deposition can be due to

acid production from dying or injured cells

Necrosis or degeneration of tissue pathway

Calcium infiltration (from an injured cell)

• free floating Ca ions in the cytoplasm (can be from inside or out of the cell)

• this is the point of no return and cell is going to die

• Calcium inside cell is no longer bound to the places where it is supposed to be (not on top of calcium binding proteins)

Necrosis

Spectrum of morphologic changes that follows cell death in living tissues

• affects groups of cells

• evoked by non-physiological events (viruses, ischemia, toxins, etc.)

• inflammation

• swelling of cytoplasm and mitochondria

• loss of plasma membrane integrity

• no energy requirement; passive process

• calcium overload a key feature

Necrosis vs Apoptosis

• necrosis:

  • During necrosis, cell swelling causes organelles to become vacuolated as the cell tries to retain excess fluid.

  • Eventually, the swollen cytoplasm and organelles crowd the cell, leading to rupture of the plasma membrane.

• apoptosis: 

  • decrease cytoplasm and package things up very neatly and so that they are nice packaged for macrophages to engulf 

apoptosis

• controlled cell death of individual cells

• induced by physiological stimuli 

• no inflammation 

• shrinking of cytoplasm and condensation of nucleus 

• blebbing of plasma membrane with no loss of integrity 

• energy (ATP)-dependent; active process; functional mitochondria 

• cell death pathway activation 

pathogenesis of necrosis

• denaturation od intracellular proteins 

• enzymatic digestion of the cell 

Coagulative necrosis 

• preservation of general tissue architecture-tombstone appearance of the cells 

• affected tissue is firm 

• denaturation of structural proteins and enzymatic digestion of cells

• ex. heart, kidney, spleen, adrenal gland

• looks like it is being turned to stone

Liquefactive necrosis

• neurons and glial cells of the brain

• hydrolytic enzymes

• bacterial infection

  • staphylococci, streptococci, and e. coli

• tissue becomes liquid viscous mass

• material is creamy yellow in color

• seen in brain, abscess

caseous necrosis

• combination of coagulative and liquefactive necrosis

• seen in tuberculous infections **** know for exam

• tissue is cheesy white in appearance

• the tissue architecture is preserved

• For tb, it is only seen in the lungs 

Fat necrosis

• seen in pancreas, breast, and other abdominal organs 

• in acute pancreatitis, activated lipase causes fat necrosis 

• grossly visible chalky white areas 

  • (broken down triglycerides-FA combine with salts = soap=saponification 

  • fatty acid + salt = soap

• presence of shadowy outlines of necrotic cells 

gangrenous necrosis

• not a type of necrosis but happens as a result of them

  • end stage of other types of necrosis 

• deahth of tissue from severe hypoxic injury (dry vs wet) 

• gas gangrene: clostridium

Wet vs Dry va Gas Gangrene 

• Wet 

  • occurs in moist tissues like mouth, bowel, lung, cervix 

  • diabetic foot 

  • bed sores 

• Dry (due to blockage of blood supply to an area)

  • toes and feet due to arteriosclerosis 

  • raynauds disease 

  • trauma 

• Gas

  • wet gangrene caused by gram positive anaerobic bacteria 

  • seen in muscle and in colon 

Various inductions of necrosis