Cell injury-2

Fatty Change * Definition: abnormal accumulation of triglycerides within parenchymal cells. * Site:  liver, most common site which has a central role in fat metabolism.  it may also occur in heart as in anaemia or starvation (anorexia nervosa)  Other sites: skeletal muscle, kidney and other organs.

* Causes: 1.Toxins (most importantly: Alcohol abuse) 2.Diabetes mellitus 3.Protein malnutrition (starvation) 4.Obesity 5.Anoxia

* The significance of fatty change:  Depends on the severity of the accumulation.  Mild: it may have no effect.  Severe: form, fatty change may precede cell death, and may be an early lesion in a serious liver disease called nonalcoholic steatohepatitis

* Morphological features of fatty liver: *Grossly: Size: enlarged. Shape: preserved. Surface: smooth. Color: yellowish. Consistency: soft & greasy. Capsule: stretched (non-adherent). C/S: bulges out with rounded edges.

*Microscopically: The cells are swollen, the cytoplasm contains droplets of fat (in mild cases) termed microvesicular steatosis, or vacuoles pushing the nucleus to one side in severe cases (signet ring appearance) termed macrovesicular steatosis. Fat appears as empty vacuoles in Haematoxyline & Eosin stained sections but stained in frozen sections by fat stains e.g. Oil Red O stain.

Fatty liver; Oil Red O stain

Disorders of Pigmentation

A. Endogenous pigmentation I. Melanin pigment Melanin deficiencyMelanin hyper pigmentation 1. Albinism -Hereditary absence of tyrosinase enzyme. -Hair is white, skin, iris, choroids are pink. 2. Leucoderma -Idiopathic or 2ry to leprosy or syphilis. -White skin patches due to melanin loss. 1. Prolonged exposure to sun. 2. Chloasma: brown patches on face, nipple & genitalia due to increased estrogen level. 3. Melanocytic tumors. 4. Addison’s disease.

Albinism Leucoderma

Chloasma Nevus

II. Lipochrome (lipofuscin) pigment It is a yellowish brown pigment, which is found normally in heart, liver, testis, seminal vesicles & adrenals. Increases in old age & in atrophic conditions e.g. Brown atrophy of the heart.

Here is the centrilobular portion of liver next to a central vein. The cells have reduced in size or been lost from hypoxia. The pale brown-yellow pigment is lipochrome that has accumulated as the atrophic and dying cells undergo autophagocytosis.

III. Hemoglobin-derived pigment BilirubinHemozoin (haematin) Hemosiderin Increases in jaundice. -ve with Prussian blue reaction increases in Bilharziasis & malaria. Released from the parasite, engulfed by the cells of RES in liver, spleen → parasitic pigmentation. -ve with Prussian blue Increases with hemosiderosis. +ve with Prussian blue.

Jaundice

Hemosiderosis * Causes of Hemosiderosis: 1.Increased absorption of dietary iron 2.Hemolytic anemias 3.Repeated blood transfusions. 4.Hereditary hemochromatosis with tissue injury including liver fibrosis, heart failure, and diabetes mellitus.

 It is found at first in the mononuclear phagocytes of the liver, bone marrow, spleen, and lymph nodes and in scattered macrophages throughout other organs.  With progressive accumulation, parenchymal cells throughout the body (principally the liver, pancreas, heart, and endocrine organs) will be affected

Hemosiderin H&E: golden brown pigment Prussian blue stain: blue

Exogenous Pigmentations

Lung anthracosis

Lymph node anthracosis

Pathological calcification It implies the abnormal deposition of calcium salts in tissues rather than bone and teeth. It has 2 types:  Dystrophic calcification:  When the deposition occurs in dead or dying tissues e.g. areas of necrosis or atherosclerotic patches.  it occurs with normal serum levels of calcium  Metastatic calcification:  The deposition of calcium salts in normal tissues  It almost always reflects hypercalcemia.

Irreversible cell injury

* Mechanism of irreversible cell injury: Persistent or severe injury (hypoxia) takes the cell to the "point of no return" where the injury becomes irreversible. At this point no intervention can save the cell. Severe mitochondrial damage is the hallmark of irreversible injury.

Mitochondrial damage Marked reduction in ATP production leads to mitochondrial damage results in formation of high conductance channels ( Mitochondrial Permeability Transition (MPT) channels) which Release cytochrome c into cytosol which is a trigger for cell death (apoptosis).

MITOCHONDRIAL DYSFUNCTION or INJURY Mitochondrial Permeability Transition (MPT) Cytochrome C ↓ATP production H+ Apoptosis

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