د.زياد

Cell Injury, Adaptations & Cell Death

Hypertrophy
Increase in protein synthesis/ organelles Increase in size of cells Increase in organ/tissue size

HYPER-TROPHY

IN-CREASE IN SIZE OF CELLS


.
This is cardiac hypertrophy involving the left ventricle. The number of myocardial fibers does not increase, but their size can increase in response to an increased workload, leading to the marked thickening of the left ventricle in this patient with systemic hypertension.

Physiologic hypertrophy (uterus during pregnancy)

normal
gravid
normal
gravid
Microscopy


Hyperplasia
Increase in NUMBER of cells Increase in size of organ/tissue Similar end result as hypertrophy May occur with hypertrophy


This is an example of prostatic hyperplasia. The normal adult male prostate is about 3 to 4 cm in diameter. The number of prostatic glands, as well as the stroma, has increased in this enlarged prostate seen in cross section. The pattern of increase here is not uniform, but nodular.
The prominent folds of endometrium in this uterus opened to reveal the endometrial cavity are an example of hyperplasia. Cells forming both the endometrial glands and the stroma have increased in number. As a result, the size of the endometrium has increased.

Hyperplasia

Atrophy
Decrease in size of cell Smaller tissue/organ Most common causes: disuse malnutrition Ischemia lack of endocrine stimulation aging denervation

ATROPHY

82-year
36-year
Gyri
Sulci
A-Physiologic atrophy of the brain in an 82-year-old male. The meninges have been stripped B-Normal brain of a 36-year-old male.



Atrophy


There are some muscle fibers here that show atrophy. The number of cells is the same as before the atrophy occurred, but the size of some fibers is reduced. This is a response innervation. The small fibers in the center was lost. This is a trichrome stain.


The testis at the right has undergone atrophy and is much smaller than the normal testis at the left.

Metaplasia

A reversible change in which one differentiated cell type is replace by another differentiated cell type. Several forms: Squamous metaplasia Cartilaginous metaplasia osseous metaplasia

METAPLASIA

Columnar to Squamous Squamous metaplasia in bronchi….. smokers Squamous to columnar type Barret esophagus

Barrett’s esophagus

Metaplasia of esophageal squamous mucosa has occurred here, with gastric type columnar mucosa at the left.



Reversible cell injury:
the cellular changes will regress and disappear when the injurious agent is removed; 1- Cloudy swelling (Hydropic changes)

2- fatty changes

Hydropic Swelling of renal tubules

FATTY LIVER

Gross exam. Large, yellow, soft and greasyCauses: alcohol, obesity, DM, …., …….

Left: Normal liver Right: Fatty change in liver. Liver from an alcoholic shows large vacuoles (V) in the hepatocytes (H) with displacement of nucleus (N).

Fatty change of the liver in which deranged lipoprotein transport from injury (most often alcoholism) leads to accumulation of lipid in the cytoplasm of hepatocytes

Hepatic steatosis in an uncontrolled diabetic

IRREVERSIBLE CELL INJURY
NECROSIS:���� is a pathological process in which cells and tissues die in a living organism ���� Affect both nucleus and cytoplasmApoptosis: death of single cells during life


NECROSIS
Cytoplasmic changes :Eosinophilia (pink) Glassy, homogenous appearanceCell membranes are fragmented Nuclear changes: Pyknosis – small and dense nucleiKaryolysis – complete lysis of the nucleiKaryorrhexis – fragmented nuclei (generally seen in apoptosis)

Renal cortex .

Centrilobular hepatocytes are pale and necrotic. Note that in the necrotic areas many of the nuclei are lost. This is karyolysis. Some of the dark nuclei that are remaining are actually endothelial cell nuclei lining the sinusoids. Note the "pre-necrotic" cells that are only at the stage of cell swelling?


Spleen with parvovirus infection has fragmentation of lymphocyte nuclei (karyorrhexis) because of the infection. Many of these nuclear changes due to apoptosis.

NECROSIS…. TYPES Coagulative:����In: infarcts of heart, kidney, spleen����Gross: pale , yellow, opaque, firm����Mic.: All cellular details are lost but general architecture of the tissue is preserved����Surrounding tissue----acute inflammation

This is an example of coagulative necrosis. Here, there is a wedge-shaped pale area of coagulative necrosis (infarction) in the renal cortex of the kidney.


Two large infarctions (areas of coagulative necrosis) are seen in this sectioned spleen. Since the etiology of coagulative necrosis is usually vascular with loss of blood supply, the infarct occurs in a vascular distribution. Thus, infarcts are often wedge-shaped with a base on the organ capsule.


NECROSIS……… TYPES Liquefactive:���� infarcts of C.N.S. centers of pyogenic abscess���� Necrotic tissue---completely liquified---turbid fluid----absorbed----space

LIQUEFACTIVE NECROSIS, BRAIN

At high magnification, liquefactive necrosis of the brain demonstrates many macrophages at the right which are cleaning up the necrotic cellular debris.
As this infarct in the brain is organizing and being resolved, the liquefactive necrosis leads to resolution with cystic spaces.



The two lung abscesses seen here are examples of liquefactive necrosis in which there is a liquid center in an area of tissue injury. One abscess appears in the upper lobe.
The liver shows a small abscess here filled with many neutrophils.


NECROSIS…… TYPES Fat necrosis:����Traumatic: in female breast����Enzymatic: in acute pancreatitis• Gross: opaque& white

Microscopically, fat necrosis adjacent to pancreas is seen here. The necrotic fat cells at the right have vague cellular outlines, have lost their peripheral nuclei, and their cytoplasm has become a pink amorphous mass of necrotic material.
Fat necrosis in acute pancreatitis. The areas of white chalky deposits represent foci of fat necrosis with calcium soap formation (saponification) at sites of lipid breakdown in the mesentery.


NECROSIS…… TYPES Caseous necrosis:Coagulative + Liquifactive necrosis����In: Tuberculosis, Fungal infections,���� Necrotic tissue is partially liquefied---cheesy material (caseation)���� Mic: Both cellular details & generalarchitecture of dead tissue are lost---structureless eosinophilic material

caseous necrosis

This is more extensive caseous necrosis, with confluent cheesy tan granulomas in the upper portion of this lung in a patient with tuberculosis.
This is the gross appearance of caseous necrosis in a hilar lymph node infected with tuberculosis. The node has a cheesy tan to white appearance. Caseous necrosis is most characteristic of granulomatous inflammation.

CASEOUS NECROSIS, TB

Microscopically, caseous necrosis is characterized by acellular pink areas of necrosis, as seen here at the upper right, surrounded by a granulomatous inflammatory process.

Gangrene

is necrosis with the putrefaction of the tissues. The affected tissues appear black due to the deposition of iron sulphide from degraded hemoglobin. 'dry' gangrene sterile; 'wet' gangrene - with bacterial putrefaction.

Gangrenous necrosis types

Fibrinoid necrosis
Immune-mediated vascular damageProtein – like material in the blood vessel walls

FIBRINOID NECROSIS

Apoptosis
Apoptosis is a more orderly process of cell death in which there is individual cell necrosis, not necrosis of large numbers of cells. In this example, liver cells are dying individually (arrows) from injury by viral hepatitis. The cells are pink and without nuclei.

syndactyly involving the third and fourth digits of the fetal hand

Accumulations and Pigmentations



LIPIDS ۞ 1- Fatty changes 2-Cholesterol and Cholesterol Esters A- In atherosclerosis, cholesterol accumulates in the intima of arteries B- In xanthomas cholesterol accumulates under the skin, forming tumor-like structures C- In cholesterolosis, there is focal accumulations of cholesterol-laden macrophages in the lamina propria of the gallbladder.
Intracellular Accumulations…

Arterial narrowing by atheroma L: Lumen A: Atheroma M: Media

atherosclerosis.

xanthelasma

Cholesterolosis. Cholesterol-laden macrophages (foam cells) from a focus of gallbladder cholesterolosis (arrow).

PROTEINS۞ rounded, eosinophilic droplets or aggregates in the cytoplasm

Protein reabsorption droplets in the renal tubular epithelium

PAS stained section of liver accumulations of alpha-1-antitrypsin

PIGMENTS ۞ A-Exogenous e.g. Carbon (coal dust), accumulation of carbon pigment in the lung give it black color called (anthracosis). Tattooing, the pigment inoculated in the skin is taken by dermal macrophages.


The black streaks seen between lobules of lung beneath the pleural surface are due to anthracotic pigment.
Here is anthracotic pigment in macrophages in a hilar lymph node.

ANTHRACOSIS

B-Endogenous pigments:1- Lipofuscin This is a yellowish brown pigment, often found in the atrophied cell or old age. It is particularly common in the heart muscle, and the term “brown atrophy” is often applied.

Lipofuscin granules in a cardiac myocyte as shown by A, light microscopy (deposits indicated by arrows), and B, electron microscopy (note the perinuclear, intralysosomal location).

lipochrome (lipofuscin)

2- Melanin Melanin is a normal pigment found in the form of fine brown granules in the skin.Local melanin pigmentation e. g. pigmented nevus, melanoma.Generalized melanin pigmentation e. g. Addison’s disease.

Congenital nevus

3-Hemosidrin : Is a hemoglobin-derived, golden- yellow to brown granules. Excess deposition is termed as hemosiderosis which is either localized or systemic. Localized hemosiderosis: result from local hemorrhage e.g. bruise.


The brown coarsely granular material in macrophages in this alveolus is hemosiderin that has accumulated as a result of the breakdown of RBC's and release of the iron in heme.

Hemosiderin granules in liver cells. A, H&E section showing golden-brown, finely granular pigment. B, Prussian blue reaction, specific for iron.

4- Bilirubin: It is a normal major pigment of bile , which is derived from hemoglobin. Jaundice: result from excess of Bilirubin pigment that is distributed throughout all tissues & body fluids
The yellow-green globular material seen in small bile ductules in the liver here is bilirubin pigment. This is hepatic cholestasis.
The sclera of the eye is yellow because the patient has jaundice, or icterus. The normally white sclerae of the eyes is a good place on physical examination to look for icterus.

Calcification

abnormal deposition of calcium salts occur in any tissues except bones and teeth. Two forms of calcification; 1- Dystrophic calcification: deposition of calcium in non viable or dying tissues. the serum calcium is normal 2-Metastatic calcification: deposition of calcium in viable tissue , the serum calcium is high. (hypercalcemia) Dystrophic calcification is noted in 1-Areas of necrosis (coagulative, Liquefactive or fatty necrosis). 2-Advavced atherosclerosis. 3-Damaged or aging heart valves. Metastatic calcification is seen in cases of hypercalcemia of any cause. It principally affect blood vessels , kidney, lungs and gastric mucosa.

View looking down onto the unopened aortic valve in a heart with calcific aortic stenosis.

This is dystrophic calcification in the wall of the stomach. At the far left is an artery with calcification in its wall. There are also irregular bluish-purple deposits of calcium in the submucosa. Calcium is more likely to be deposited in tissues that are damaged.


Here is so-called "metastatic calcification" in the lung of a patient with a very high serum calcium level (hypercalcemia(
Here is so-called "metastatic calcification" in the lung of a patient with a very high serum calcium level (hypercalcemia).