Degenerative Changes/

Morphology of reversible cell injury

Dr. Ram Thapa

Pathologist
 Degenerative Changes
 The term degeneration was commonly used to denote
morphology of reversible cell injury
REVERSIBLE CELL INJURY
Morphologic forms are:

1. Hydropic change

2. Hyaline change

3. Mucoid change

4. Fatty change
 Hydropic change
 Accumulation of water within the cytoplasm of the cell.

 A/K cloudy swelling (for gross appearance of the affected organ)

and vacuolar degeneration (due to cytoplasmic vacuolation).

 Commonest and earliest form of cell injury from almost all

causes

 Cloudy swelling results from impaired regulation of sodium and

potassium at the level of cell membrane
 Hydropic change
▪ Causes are :- acute and subacute cell injury from various
etiologic agents such as bacterial toxins, chemicals, poisons,
burns, high fever, intravenous administration of hypertonic
glucose or saline

▪ Pathogenesis -cloudy swelling results from impaired

regulation of sodium and potassium at the level of cell
membrane
 Hydropic change –morphology

Grossly, the affected organ is enlarged due to swelling.

Microscopically –
➢ cells are swollen and their cytoplasm contains small clear
vacuoles and hence the term vacuolar degeneration.
➢ vacuoles represent distended cisternae of the endoplasmic
reticulum.
➢ Small cytoplasmic blebs may be seen.
➢ The nucleus may appear pale.
Hydropic change -Microscopically

 Vacuolar degeneration, Small cytoplasmic blebs, pale nucleus

 MUCOID CHANGE
 Mucoid change is deposition of mucinous material in epithelial
and connective tissues in excessive amounts

 Mucin is normally produced by epithelial cells of mucous

membranes and mucous glands, as well as by some connective
tissues

 Mucin are stained by alcian blue

 Epithelial mucin
Functional excess of epithelial mucin:
1. Catarrhal inflammation of mucous membrane (e.g. of
respiratory tract, alimentary tract, uterus).

2. Obstruction of duct leading to mucocele in the oral cavity and

gallbladder.

3. Cystic fibrosis of the pancreas.

4. Mucin-secreting tumours (e.g. of ovary, stomach, large

bowel etc)
Connective tissue mucin
1. Mucoid or myxoid change in some tumours e.g. myxomas,
neurofibromas, fibroadenoma, soft tissue sarcomas

2. Dissecting aneurysm of the aorta due to medial degeneration

and Marfan’s syndrome.

3. Myxomatous change in the dermis in myxoedema.

4. Myxoid change in the synovium in ganglion on the wrist

INTRACELLULAR ACCUMULATIONS
 Metabolic derangements

 Intracellular accumulation of substances

 May be harmless or cause further cell injury

 Location of accumulations are in the cytoplasm, within

organelles (typically lysosomes), or in the nucleus,
 Intracellular Accumulations
Four main mechanisms are :

➢ Inadequate removal of a normal substance secondary to defects in

packaging and transport,

➢ Genetic or acquired defects in its folding, packaging, transport, or

secretion,

➢ Failure to degrade a metabolite due to inherited enzyme deficiencies,

➢ Deposition and accumulation of an abnormal exogenous substance

Intracellular Accumulations
Various substances are
 Lipids

 Proteins

 Glycogen

 Pigments
Intracellular Lipids Accumulations
All major classes of lipids can accumulate in cells

➢ Triglycerides,

➢ Cholesterol/cholesterol esters,

➢ Phospholipids
 Steatosis (Fatty Change)
 Abnormal accumulations of triglycerides within parenchymal
cells

 Often seen in the liver but it also occurs in the heart, muscle, and
kidney

 Causes of steatosis include toxins, protein malnutrition, diabetes

mellitus, obesity, Metabolic syndrome and anoxia

 Significant fatty change in the liver are alcohol abuse and

nonalcoholic fatty liver disease,
 Fatty Liver- Steatosis
 intracellular accumulation of neutral fat within parenchymal
cells
 fatty change may be mild and reversible, or severe producing
irreversible cell injury

Etiology:-
1.Conditions with excess fat- Obesity, Diabetes mellitus
, hyperlipidaemia
2. Liver cell damage -Alcoholic liver disease (most
common),Starvation,Acute fatty liver in late
pregnancy,Hepatotoxins (e.g. carbon tetrachloride, chloroform,
ether, aflatoxins, Drug-induced liver cell injury
 Fatty Liver- Pathogenesis

1. Increased entry of free fatty acids into the liver.

2. Increased synthesis of fatty acids by the liver.
3. Decreased conversion of fatty acids into ketone bodies
resulting in increased esterification of fatty acids to triglycerides.
4. Increased esterification of fatty acids to triglycerides.
5. Decreased synthesis of ‘lipid acceptor protein’ resulting in
decreased formation of lipoprotein from triglycerides.
6. Block in the excretion of lipoprotein from the liver into
plasma.
 Fatty Liver- Pathogenesis..

Liver cell injury from chronic alcoholism is multifactorial as

follows:
➢ Increased lipolysis
➢ Increased free fatty acid synthesis
➢ Decreased triglyceride utilization
➢ Decreased fatty acid oxidation to ketone bodies
➢ Block in lipoprotein excretion
 Steatosis - Morphology
Grossly, The liver is enlarged with
a tense, glistening capsule, soft,
the liver in fatty

The cut surface bulges slightly and

is pale-yellow to yellow and is
greasy to touch
Steatosis - Morphology
 Steatosis – Morphology..
 Microscopically, characteristic feature is the presence of
numerous lipid vacuoles in the cytoplasm of hepatocytes
➢ The vacuoles are initially small and are present around the
nucleus (microvesicular).
➢ With progression of the process, the vacuoles become larger
pushing the nucleus to the periphery of the cells
(macrovesicular)
Steatosis (Fatty Change)
Steatosis (Fatty Change)
 Intracellular Lipids Accumulations

Cholesterol and Cholesterol Esters :- Histologically by intracellular

vacuoles are seen in

➢ Atherosclerosis :

➢ Xanthomas: Intracellular accumulation of cholesterol within

macrophages is also characteristic of acquired and hereditary
hyperlipidemic states

➢ Cholesterolosis: focal accumulations of cholesterol-laden

macrophages in the lamina propria of the gallbladder
Intracellular Lipids Accumulations
 Intracellular Proteins Accumulations
 Usually appear as rounded, eosinophilic droplets, vacuoles, or
aggregates in the cytoplasm

 By electron microscopy, they can be amorphous, fibrillar, or

crystalline in appearance

 Reabsorption droplets in proximal renal tubules are seen in renal

diseases (proteinuria cases)

 Defective intracellular transport and secretion of critical proteins

e.g In α1-antitrypsin deficiency,
Intracellular Proteins Accumulations

 Accumulation of cytoskeletal proteins

 Aggregation of abnormal proteins :-can be intracellular,

extracellular, or both.
 Hyaline Change
 word ‘hyaline’ or ‘hyalin’ means glassy (hyalos = glass)
 An alteration within cells or in the extracellular space that gives a
homogeneous, glassy, pink appearance in routine histologic (H&E
stain)
 Proteins and plasma proteins

 Intracellular hyaline and Extracellular hyaline

 Intracellular hyaline accumulations of protein include reabsorption

droplets, Russell bodies, and alcoholic hyaline.
 Hyaline Change
Intracellular Hyaline

 Hyaline droplets in proteinuria

 Hyaline degeneration in typhoid fever

 Nuclear or cytoplasmic hyaline inclusions seen in some viral

infections.

 Russell’s bodies in MM
Intracellular Hyaline
 Hyaline Change
Extracellular Hyaline

 Hyaline degeneration in leiomyomas

 Hyalinised old scar

 Hyaline arteriolosclerosis in renal vessels in hyper tension and

diabetes mellitus.

 Hyalinised glomeruli in chronic glomerulonephritis.

 Corpora amylacea in BPH

Extracellular Hyaline
 Glycogen Accumulations
 Glycogen is a readily available source of glucose stored in the
cytoplasm of healthy cells

 Excessive intracellular deposits of glycogen are seen in patients

with an abnormality in either glucose or glycogen metabolism

 Glycogen masses appear as clear vacuoles within the cytoplasm (In

H&E stain)
Glycogen Accumulations
 Glycogen Accumulations

 In Diabetes mellitus,glycogen is found in renal tubular epithelial

cells, within liver cells, β cells of the islets of Langerhans within
the pancreas, and heart muscle cells

 Glycogen storage diseases : Glycogen accumulates within select

cells
 Pigments Accumulations
Endogenous pigments These substances are produced either within
tissues and serve a physiological function, or are by-products of
normal metabolic processes.

Subdivided into:
1. Hematogenous (blood-derived) pigments
2. Non-hematogenous pigments
3. Endogenous minerals
 Pigments Accumulations

Hematogenous (blood-derived) pigments are :

 Hemosiderins
 Hemoglobin
 Bile pigments
 Porphyrins

Non-hematogenous endogenous
pigments are:
▪ Melanins
▪ Lipofuscins
▪ Chromaffin
▪ Others
 Pigments Accumulations
3. Exogenous pigments and minerals:- These substances gain access
to the body accidentally through a variety of methods e.g. carbon
anthracotic pigment,
 Lipofuscin Pigments
 Lipofuscin or lipochrome is yellowish-brown intracellular lipid
pigment (lipo = fat, fuscus = brown).

 The pigment is often found in atrophied cells of old age and

hence the name ‘wear and tear pigment’.

 It is seen in the myocardial fibres, hepatocytes, Leydig cells of the

testes and in neurons in senile dementia
Lipofuscin Pigments ..
 By light microscopy, the pigment is coarse, golden-brown
granular and often accumulates in the central part of the cells
around the nuclei.

 By electron microscopy, lipofuscin appears as intralysoso mal

electron-dense granules in perinuclear location

 Lipofuscin granules are composed of lipid-protein

complexes.
Lipofuscin Pigments
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