Cellular Injury Intracellular degeneration By Dr. Hemn Hassan Othman PhD, Pathology Fall 2018 10/20/2018 1
Types of cell injury Cell injury is divided into: 1. Reversible cell injury 2. Irreversible cell injury Reversible cell injury It is a type of cell injury in which the pathological changes will regress and disappear when the injurious agent is removed and the cells will return to normal morphological and functional status. Irreversible cell injury It is a type of cell injury which occurs when the injurious agent persists or when it is severe from the beginning. At first the injury is reversible, but later it reaches the point of no return, where it becomes irreversible. 10/20/2018 2
Point of no return It is the precise moment of transition from reversible to irreversible cell injury. At this point, no adaptation can save the cell and the progression to cell death is inevitable (unavoidable). 10/20/2018 3
10/20/2018 4
For example, If the blood supply to a portion of the heart musculature is cut off for few minutes and then restored; the affected myocardial cells will sustain reversible injury, i.e., after restoration of the blood it will recover and function normally (as in mild cases of angina pectoris). But if the cessation of blood supply continues from 30 to 60 minutes and then restored, the affected myocardial cells will suffer from irreversible injury (Cell Death). 10/20/2018 5
Cell death Two phenomena characterize irreversibility 1. Inability to reverse mitochondrial dysfunction 2. Development of profound disturbances in membrane function 10/20/2018 6
Classification of cell death 1) Necrosis Result of catastrophic injury to the mechanisms that maintain cell integrity 2) Apoptosis Result of genetically determined cell-death (programmed cell death). 10/20/2018 7
10/20/2018 8
Reversible Cell Injury (Degeneration): Degenerations Definition: When cellular injury is sub lethal and sustained, cells and tissues tend to accumulate substances in abnormal quantities. These materials may be endogenous or exogenous. Location: Intracellular and/or Extracellular 10/20/2018 9
( 1 ) Intracellular edema (Cellular swelling, cloudy swelling, hydropic degeneration) Definition: Accumulation of watery fluid in cells. Morphologic change: Gross features: Swelling and paleness to the organ. Light microscopic features( LM): Parenchymal cells swollen. 10/20/2018 10
Early stages: Granularity degeneration a fine granularity like ground-glass in the cytoplasm. Later stages: Hydropic degeneration clear vacuoles in the cytoplasm Progressive dilatation of the swollen cell. 10/20/2018 11
10/20/2018 12
Left Granularity change in kidney Right Hydropic change 10/20/2018 13
10/20/2018 14
10/20/2018 15
10/20/2018 16
10/20/2018 17
Leukoedema (Geographical Tongue) Migratory Glossitis 10/20/2018 18
Mechanism hydropic degeneration: Lack of oxygen (Hypoxia). Toxic materials. Osmotic effect. 10/20/2018 19
Pathogenesis of cellualr swelling: Damage to mitochondria or its enzymatic pathways. The diminished formation of ATP affects all the energy requiring reaction in the cell but in particular leads to failure of the sodium pump. Sodium ions enter the cell in exchange for potassium and as the former have a larger hydration shell, there is a net influx of water. 10/20/2018 20
Liver 10/20/2018 21
10/20/2018 Kidney/ Cortex 22
Kidney / Tubular epithelium 10/20/2018 23
(2) Fatty change (Fatty Degeneration): Definition: There is an accumulation of neutral fat (triglycerides) in the parenchyma of non-fatty cells e.g. Liver, Heart, Kidneys. Gross features: The organ enlarges and becomes yellow, soft, and greasy to touch. LM: Fatty change appears as clear vacuoles within parenchymal cells pushing the nucleus to periphery of the cell. 10/20/2018 24
Liver: Since this organ plays a central role in fat metabolism, the accumulation of fat in toxic conditions can be very considerable, fatty distribution varies with the cause, e. g. : Poison, Toxins, alcohol, infections, organic solvents etc. 10/20/2018 25
10/20/2018 26
10/20/2018 27
Fatty change of liver Left: Gross photograph Center: HE Stain Right: Oil Red-O Stain 10/20/2018 28
Gross & microscopic appearance of fatty changes 10/20/2018 29
Fatty liver change 10/20/2018 30
Heart: It occurs in two patterns, in one, prolonged moderate hypoxia, such as that produced by profound anemia, causes intracellular deposits of fat, which create grossly apparent bands of yellowed myocardium alterations with bands of darker, red-brown, uninvolved myocardium (tigered effect). In the other pattern of fatty change produced by more profound hypoxia or myocarditis, the myocardial cells are uniformly affected. 10/20/2018 31
10/20/2018 32
Fatty Degeneration in the heart 10/20/2018 33
Kidney: In most cases fatty change is confined to the epithelium of the renal tubules, but in severe poisoning it may affect all structures including the glomerular. 10/20/2018 34
Glomeruli Renal tubules 10/20/2018 35
Causes: Poisons. e. g. carbon tetrachloride, phosphorus (liver) Chronic alcoholism (liver) Infections Congestive cardiac failure Severe anemia Ischemia Diabetes mellitus Malnutrition and wasting disease. 10/20/2018 36
Mechanism: Impaired metabolism of fat. Impaired secretion of fat. Excessive triglyceride into the cell. 10/20/2018 37
10/20/2018 38
Fatty Infiltration: Fatty infiltration, in contrast to fatty change, describes infiltration by normal-appearing lipocytes into the interstitial connective tissues of organs that do not normally contain appreciable quantities of adipose tissue. It occurs commonly in the heart and pancreas and is often found along with obesity. 10/20/2018 39
Fatty infiltration of heart 10/20/2018 40
10/20/2018 Fatty infiltration of heart 41
10/20/2018 42
10/20/2018 43
Fatty infiltration of heart 10/20/2018 44
Fatty infiltration of pancrease 10/20/2018 45
3. Glycogen Deposition : Excessive accumulations of glycogen may occur pathologically in the cytoplasm of epithelial cells of the liver and kidneys. Causes : 1) Hyperglycemia, as occurs in diabetes mellitus. 2) Steroid-induced hepatopathy. 10/20/2018 46
Glycogen Deposition 10/20/2018 47
(4) Intracellular Hyaline change: Definition: It s The accumulation of protein in the cytoplasm of cells, usually in the form of isolated eosinophilic droplets, is termed hyaline droplet formation. 10/20/2018 48
Pathogenesis: It is seen most often in the cytoplasm of epithelial cells of the renal tubules. Plasma proteins leak from abnormal glomerular capillaries and are resorbed from the lumens of the tubules. If protein leakage exceeds the absorptive capacity of these cells, eosinophilic albuminous or hyaline casts are present in the 10/20/2018 tubular lumens. 49
Types of Intracellular hyaline: Restorative droplets: The cytoplasm of renal tubules filled with plasma protein during proteinuria. 10/20/2018 50
Protein reabsorption droplets in the renal tubular epithelium 10/20/2018 51
Mallory alcoholic bodies: liver cytoplasmic aggregates of fragmented fine filaments and tubules, derived from hepatocytes cytoskeleton. 10/20/2018 52