Pathology

Pathology 081700 – 1400 Thursday Dr. Graham Scribes: Chu & Kang Introduction: Cell Injury and Adaptation  Apoptosis vs. Necrosis o Causes: depends on type of injury and degree of injury o Classic coagulative necrosis cause ischemia. Ex. Ischemia of heart secondary to complete obstruction of LAD (Left Anterior descending a.) o Viral Infection of liver causes apoptosis (single cell death) Note: clinically terms used loosely. o Little ischemia is apoptosis, however ischemia is classically defined as necrosis. o Viral infections, classically lead to apoptosis, but too much can lead to necrosis. o Endocrine related changes/withdrawal and graft vs. host injury/immune injury lead to apoptosis. o Morphological changes: Necrosis – the cell balloons up due to leaky membrane, and disintegrates by enzymatic digestions or is mummified by protein degradation. It also causes all kinds of inflammatory responses (responses due to bacterial causes an increase in neutrophils, responses due to parasites cause an increase in eosinophiles). Inflammatory responses also lead to hyperemia (creation of new blood vessels to bring in immune cells. Apoptosis: shrivel up and die. They shrivel up, break apart in enclosed packages (apoptotic bodies), and phagocytes eat them up. o Referring to liver slide: bright apoptotic cell all shriveled up with councilman bodies (shrunken little dead cell). Not lots of neutrophils or lymphocytes around, but will eventually engulf the apoptotic cells. o Diagram in Robin (Fig. 1-16): shows differences between necrosis & apoptosis. o Necrosis and apoptosis can take place in the same region, difficult to tell. o This is a vocabulary lesson: i.e. know cytoskeletons.  Thin filaments and microtubules functions in motility. If problematic, diseases such as Kartagener syndrome (no sperm motility) can develop or bronchi lining can’t clear because of immobility of cilias.  Cytokeratin is a better term than keratin. It’s an intermediate filament 10 nm in size and ubiquitous (primarily in epithelial cells) used differentitially to tell epithelial cells apart. For instance, liver has mallory bodies (charcteristic of reactions to injury where there are a lot of fatty changes as in alcohol abuse). They are “ropey,” irregular, red, eosinophilic accumulations in the cytoplasm of the liver. They help in identification of liver cells. For example when looking at different tumor cells.  Neurofilaments can help us identify number of things in the neural axis. Desmin is seen in muscle. Vimentin in mesenchymal tissues. Glial filaments in glial tissues. They can help define tissues, describe tissues, and how specific tissues respond to injury. Adaptation o Hyperplasia: increase in number of cells  Tissues that can divide can be hyperplastic: blood, skin, smooth muscle, gut.  Tissues that can’t divide can’t be hyperplastic: skeletal muscles, cardiac muscles.  Epithelial and mesenchymal cells must proliferate naturally to undergo hyperplasia.  Morphologically cells are fluffy and bigger than normal.  Physiological hyperplasia: things that normally occur. i.e. normal estrogen levels,  Pathological hyperplasia: occurs after injury or abnormalities. i.e. too much estrogen, viral infection.  Ideally, hyperplasia is reversible. If you take away the trophic substance or injury (i.e. the virus), lots of hyperplasia go away. If you stop wearing a shoe, your thick skin goes away from not needing to wear the straps. However, the longer the hyperplasia lasts, it can be irreversible.  Normally glands in the endometrium are spaced, but if one receives too much estrogen, pathological hyperplasia occurs where there are too many glands too closely clustered together. If unstopped, it will lead to dysplasia or premalignant conditions. o Hypertrophy: single cell gets bigger and the cytoplasmic organelle gets more complex and bigger because it has more work to do  It is a response to an increase work load or stress.  Organ that can’t divide hypertrophies: i.e. cardiac muscles, skeletal muscles.  Question: so can smooth muscles can be hyperplastic and hypertrophic. Answer: yes, hyperplastic and hypertrophic cells will end up looking bigger.   Slide shown: thyroid: goiter (enlarged thyroid) due to hyperplasia. Must know what organ it is to know if it’s hyperplastic or hypertrophic.  Slide shown: skin: thickened epidermis due to hyperplasia.  Slide shown: heart: enlarged heart shown due to hypertrophy b/c heart can’t divide  Slide shown: bladder: large ulcer from malignant cancer, with ridges. It has a trabeculated pattern, which implies smooth muscle hypertrophy that resulted from obstruction from a tumor or urethral obstruction or prostate problem. Trabeculation is a smooth muscle hypertrophy acting against obstruction.  Slide shown: prostate: 3-5x larger than normal (80gm, normal 20gm). The terms hyperplasia and hypertrophy are used loosely in a clinical setting. Ex. Benign Prostatic Hypertrophy (BPH) is mostly due to hyperplasia rather than hypertrophy. o Atrophy: due to lack of activity, lack of use, and an increase in age  Cell likes to conserve energy; you don’t need it, you loose it.  Shrinks, gets smaller, and then goes through apoptosis.  Protein degradation: eat something or eat yourself (ubiquitin-proteasome pathway: process that degrade unneeded protein. Explained nicely in the book , Robbins pg 36).  Slide shown: testicular atrophy – much smaller than normal. o Metaplasia: reprogramming of cells to be something different; transfer of one type of mature normal cell to another type.  i.e. stomach cells becoming intestinal cells.  Helicobacter pylori causes ulcer and your body reacts to the injury by undergoing metaplasia by transforming stomach cells to intestinal cells.  Slide shown: cervix – ectocervix is squamous, and endocervix is glandular. Because it is constantly beat up throughout life, your body responds to the injury by transforming endocervix cells to ectocervix cells for more protection.  Metaplasia is completely reversible, but prolonged metplasia can lead to permanence (dysplasia). Accumulations o Lipids  Slide shown: normal liver vs. yellow liver. If something is yellow, it’s fatty unless proven otherwise. This is your liver after a night out in the town (the fatty liver, she was serious).  Use of alcohol will stop the liver from processing triglycerides, which leads to accumulation of triglycerides leading to a yellow liver. So it’s a paradigm for steatosis (fatty degeneration).  Do Oil Red O stain to identify fat.  Cholesterol is collected in macrophages and the macrophages become foamy. When you have huge amounts of it, you dump it out in the surrounding tissue leaving you with these huge cholesterol clefts or crystals.  Slide shown: people with hyperlipidemia with fatty yellow tissues (protusions) around the eyes xanthomas o Proteins  You can accumulate proteins, if you have chaperon problems in protein folding, such as alpha-1 antitrypsin deficiency. Special tests reveal accumulation of red blobs.  Glycogen can accumulate. Too much of it in diabetes or in glycogen storage diseases. May appear similar to fat, but with PAS (periodic acid Schiff) stain with diastase (?) you can tell the difference. Diastase is an enzyme that digests glycogen (ex. Spit), you spit on the sample and see glycogen dissolve. o Pigments  Slide shown (webpath 148): carbon lining the lung. Exogenous pigmentation and deposition on lobules. No pathological response. When carbon blackens tissue of lung, it’ called anthracosis.  Lipofuschin: breakdown of lipid peroxidation. You see it in the liver, fine yellow brown pigments. Not damaging. Can be seen in aging heart.  Melanin - marker of “neeva?” nevus, maybe? cells. Brown-black stain. Malignant melanoma really looks black and lumpy.  Iron (Prussian blue stain) - Iron is a pigment that can damage cells particularly the liver.  Hemosiderin - one of the iron breakdown pigments broken down from old blood (golden yellowbrown pigment in which iron is stored). Because it undergoes Fenton reaction (Fe3+ catalyze free  o radical formation) and accumulate, it can do radical damage to various organs, like the liver. Special stains to identify: Prussian Blue, iron will show up blue.  Bilirubin – Major pigment (yellow-brown) found in bile that doesn’t contain iron. liver, gall bladder, or blood breakdown that results in jaundice can see mostly in sclera of the eyes. Calcification  Dystrophic calcification: normal calcium metabolisim overall, but has local effects. If it’s at the wrong spot, it can cause functional disability. Ex. Heart valve  Metastatic calcification: abnormal calcium metabolism, like people with elevated calcium levels, people with renal diseases, hyperparathyrodism. You deposit calcium in alkaline region like the lung, but don’t have functional abnormalities.