General pathology Robbins ch1

Component cells are dead, but the besic tissue architecture is preserved. Firm texture. The injury denatures structural proteins, enzymes --> block proteolysis of dead cells --> eosinophilic, anucleate cells. Characterisitic for infarct.

Seen in focal bacterial (and fungal) infections, because microbes stimulate the accumulation of inflammatory cells and the enzymes of leukocytes "digest"/liquefy the tissue. Hypoxic death of cells in CNS evokes liq.necr. If the reaction was initiated by acute infl; the material is called pus.

(not destinctive pattern of cell death)
Applied to a limb that has lost blood supplie, and underwent coagulative necrosis in multiple layers. "Wet gangrene" if infection is superimposed by bacteria.

Most often in foci of tuberculous infection. Micro: collection of fragmented or lysed cells with amorphus granular apperance. Tissue arcithecture completely obliterated. Often in granuloma.

Focal areas of fat destruction, typically resutling from release of activated pancreatic lipases into the substance of pandreas and the peritoneal cavity. Occurs in acute pancreatitis. Micro: shadowy outlines of necrotic fat cells with basophilic calcium deposits, surrounded by infl.reaction.

Usually seen in immune reaction on blood vessels; immune complex deposits and fibrin = "fibrinoid" (bright pink amorphous apperance in H&E stain)

Cell swelling (depletion of ATP, Na leak, water enters)
Cytoplasmic Fatty Change (altered lipid metabolism)
Blebs on cell surface with loss of microvilli
Nuclear chromatin clumping
ER swelling / detachment of ribosomes
Small densities in mitochondria

Cytoplasmic eosinophilia (loss of ribonucleoproteins)
Nuclear shrinkage / pyknosis / karyolysis / karyorrhexis
Cell membrane defects and myelin figures
Large mitochondrial deposits / swelling of mitochondria
Swelling of lysosomes, lysis of ER Loss of coenzymes and RNA
If reperfused, influx of calcium; calcification

Histamine
PAF
Leukotrienes C,D,E
Serotonin
C3a
Bradykinin

Prostaglandins E,D,I
Serotonin
Bradykinin

Thromboxane A2
Leukotrienes C,D,E

C5a Interleukin-1 (indirectly)
C3a Leukotriene B4
Endotoxin

Fc fragment of IgG
C3b

Bradykinin
Leukotrienes

Thromboxane A2 promotes Prostacyclin inhibits

Bradykinin
PGE2

Interleukin-1
TNF
Prostaglandins

Increased eosinophilia, glassy homogenous apperance (due to loss of glycogen), myelin figures(phospholipid masses form damage cell membr), calcified, discontinuation of membr, dilatation of MIT, nuclear changes culmunating in nuclear dissolution.

1. kayolysis: basophilia of the chromatin fade
2. pyknosis: nuclear shrinkage and increased basophilia, DNA condenses
3. karyorrhexis: the pyknotic nucleus undergoes fragmentation

In nutrient-deprived cells, organelles are enclosed in vacoules that fuse with lysosomes. The organelles are digested but in some cases indigestible pigment (e.g lipofucin) remains

Cell exposed to toxins that are metabolized in the SER show hypertrophy of the ER, a compensatory mechanism to maxmize removal of toxins

MIT may alter in number, shape size and function. Cellular hypertrophy: increased number of MIT.
Atrophy: decreased number.
Nutritional deficiencies: megaMIT in hepatocytes.
Mitochondrial myopathies: increased numbers of unusually large MIT containing abnormal cristae.

Some drugs and toxins interfere with the assembly and functions of cytoskeletal filaments or result in abnormal accumulation of filaments

-diminished blood flow to a tissue
-most common cause of cell injury
-deprivement of nutrients

failure of many energy-dependent systems;
- ion pumps
- depletion of oxygen stores
- reduction of protein synthesis

1. if oxygen is restored; reversible
2. if persistance; irreversible injury and necrosis

Under certain circumstances , the restoration of blood flow to ischemic but otherwise viable tissues results in exacerbated and accelerated injury. As a result, tissues sustain the loss of cells in addition to those that are irreversibly damaged. Clinically important process in myocardial and cerebral infarctions.

1. increased generation of ROS from parenchymal and endothelial cells and from infiltrating leukocytes
2. inflammation may increase due to influx of leukocytes and plasma proteins
3. activation of complement system

Serves to eliminate cells that are no longer needed and to maintain a steady number of various cell population in tissues

- the programmed destruction of cells during embryogenesis (implantation, organogenesis, developmental involution, metamorphosis)
- involution of hormone-dependent tissues upon hormone deprivation (endometrium)
- cell loss in proliferating cell populations
- death of cells that have served their function
- elimination of potentially harmful self-reavtive lymphocytes
- cell death induced by cytotoxic T cells

Elimination of cells that are genetically altered or injured beyond repair without eliciting a severe host reaction, thus keeping the damage as contained as possible

- DNA damage (if injury is mild)
- accumulation of misfolded proteins leads to ER stress
- pathologic atrophy in parenchymal organs after duct obstruction (pancreas, parotid gl, kidney)

1. abnormal metabolism (fatty liver)
2. defect in protein folding, transport (accumulation of abnormal proteins)
3. lack of enzyme ( lysosomal storage disease: accumulation of endogenous materials)
4. Ingestion of indigestible materials (accumulation of exogenous materials)

1. cellular poisoning; bacteria, chemicals (chloroform, alcohol)
2. clinical disorders; anorexia (due to anemia, cardiac failure, respiratory disease), DM, chronic malnutrition

Fatty changes is seen farest away from the blood supplie (hepatic arteriole), around the efferent vein (hepatic venule)

Fatty changes is seen nearest the afferent blood supplie (hepatic arteriole and portal venule)

1. prolonged, moderate hypoxia (as in profound anemia): focal IC fat deposits, creating bands of yellowed myocardium alternating with bands of darker, red-brown, uninvolved heart "tigered effect"
2. profound hypoxia or toxic injury (eg diptheria). Uniformly affected myocytes

1.foam cells; macrophages in contact with the lipid debris of necrotic cells or abnormal forms of lipoproteins are filled with phagocytosed lipid
2. in atherosclerosis; smooth muscle cells and macroph are filled with chol and chol esters, gives characteristic yellow colour
3. Hyperlipidemic syndromes; macroph accumulate IC chol. Xanthomas=clusters of foamy macroph in subepithelial CT of skin or tendons

1. In nephrotic synrdome it is protein leakage across the glomerular filter, and mush larger reabsorbtion: Pink, hyaline cytoplasmic droplets in renal tubular epi.
2. Russell bodies: accumulation of newly synthesized Ig in RER of plasma cells
3. Mallory body /"alcoholic hyalin": eosinophilic cytoplasmic inclusion du to liver cell injury
4. Alzheimer: disrupted neuronal cytoskeleton forms neurofibrillary tangle

Carbon: air pollutant, inhaled ->phagocytosed by alveolar macroph. -> transported to regional tracheobronchial LYN
Aggregates: anthracosis
Heavy accumulations may induce emphysema or a fibroblastic reaction that may result in a serious lung diseas; worker's pneumoconiosis

Lipofuscin
Melanin
Certain derivates of hemoglobin

"wear-and-tear pigment". Insoluble brownish-yellow granular IC materials that accumulates in a variety of tissues as a function of age or atrophy. Marker of past free-radical injury. In large amount: brown atrophy

Brown-black pigment produced in melanocytes in epidermis, act as screen against harmful UV. Basal keratinocytes and dermal macrophages may accumulate the pigment.

Hb-derived granular yellow-brown pigment, accumulates in whit local or systemic iron excess. Abnormal large amount of ferritin micelles (=iron + apoferritin). Visualized with Prussian blue. Small amounts are physiological in BM, spleen,m liver).

1. Local excess of iron due to hemorrhage, eg: bruise
2. Systemic = hemosiderosis. First in mononclr phagocytes of the BM, spleen, liver, LYN, progressvie accumulation, parenchymal cells in the body(mainly liver, pancreas, heart, endocrine organs) becomes bronzed.

1. increased absorbtion of dietary iron
2. impeared utilisation of iron
3. hemolytic anemias
4. transfusions
5. hereditary hemochromatosis

Deposition of calcium in dead or dyning tissues. Occures in the absence of calcium metabolic derangements (ie normal serum levels of calcium). Intra- and/or extracellular basophilic deposits. In time, heterotrophic bone may be formed.

Almost always reflects some derangements in calcium metabolism (hypercalcemia). Principally affects the interstitiall tissue of vasculature, kidneys, lungs, and gastric mucosa

1. increased secretion of parathyroid hormone
2. destruction of bone due to accelerated turn over (eg Paget d), immobilization, tumours
3. vitamin D-related disorders (vitD intoxication, sarcoidosis)
4. renal failure (phosphate retention leads to 2ndary hyperparathyroidism)

The result of a progressive decline in the proliferative capacity and life span of cells and the effects of continous exposure to exogenous factors that cause accumulation of cellular and molecular damage

- DNA damage
- decreased cellular replication (terminal nondividing stage:replicative senescence)(short telomeres)
- reduced regenerative capacity of tissue stem cells
- accumulation of metabolic damage

Characterized by mature aging. Cells have reduced life span