PATHOLOGY &

MICROBIOLOGY-I
Resource Person: Dr. Izza Waheed
Course Code: SHS. 301
Lecture # 4: Intracellular accumulation
 LECTURE OUTLINE

• Pathways to intracellular accumulation

• Examples of intracellular accumulation
• Pathologic calcification
 LEARNING OUTCOMES

• Students shall be able to understand the reason behind intracellular

accumulation
• Students shall comprehensively describe the mechanism involved in
intracellular accumulation
• Students shall understand various forms of intracellular accumulation
• Students shall gain an insight to pathologic calcification
 INTRACELLULAR ACCUMULATION

• Accumulation of abnormal substances within the cell due to

manifestations of metabolic derangements in the cell.
• Location of accumulated substances Cytoplasm (lysosomes)
Nucleus
Elsewhere in the cell
• Abnormal substances may be water, lipid, protein. The substance may
be one of the two types
Endogenous Exogenous
Products of abormal metabolism (pigment) Infectious agent, mineral
 MAIN PATHWAYS OF INTRACELLULAR
ACCUMULATION
• Mechanism 1 involves
abnormality in metabolic
reactions e.g, fatty change in
liver
• Mechanism 2 involves mutation
in protein folding & transport
resulting in accumulation of
abnormal proteins in the cell
 MAIN PATHWAYS OF INTRACELLULAR ACCUMULATION

• Mechanism 3 involves deficiency

of an enzyme needed to catalyse
the breakdown of a substrate
resulting in accumulation of
substrate in the lysosomes
(lysosomal storage disease)
• Mechanism 4 involves
accumulation of exogenous
material as the cell in unable to
degrade phagocytosed particles
EXAMPLES OF INTRACELLULAR ACCUMULATION

• Intracellular accumulation manisfests itself in one of the following

types:
1. Fatty change
2. Cholesterol & cholesteryl esters
3. Proteins
4. Glycogen
5. Pigments
FATTY CHANGE

• Termed as “steatosis”
• Accumulation of triglycerides in parenchymal cells
• Most often associated with organs involved in lipid metabolism
such as liver
• May be seen in heart, skeletal muscle, kidney & other organs
Causes of steatosis
Toxin, malnutrtition, diabetes mellitus, obesity, anoxia

• Hepatic steatosis occurs due to type 2 DM + obesity & alcohol

abuse
FATTY LIVER
 CHOLESTEROL & CHOLESTERYL ESTERS

• Cholesterol metabolsim is crucial

to cell membrane generation

Causes of overload of cholesterol in phagocytic

cells
Decreased catabolism

Increased intake
 PROTEINS

• Difficult visualization morphologically in comparison to steatotis

• The cell may synthesize proteins or may be presented in excess to the
cell
• Nephrotic syndrome may result in abnormal reabsorption of albumin
resulting in histologic appearance of pink, hyaline cytoplasmic
droplets, the process is reversible
• Eosinophlic russell bodies may be observed on RER due to excessive
accumulation of immunoglobulins
 GLYCOGEN

• Abnormality in glucose/glycogen metabolism

• Glycogen accumulates in renal tubular epithelium, cardiac myocytes
& Beta cells of islets of Langerhans in DM.
• Abnormal glycogen accumulation may also occur in genetic diseases
such as glycogenoses or gylcogen storage diseases
 PIGMENTS

• Coloured substances
Exogenous Endogenous
Carbon (most common) Lipofuscin
Melanin
Deriatives of hemoglobin

• Carbon when inhaled causes aggregates of black pigment in lymph

nodes & pulmonary parenchyma termed as anthracosis
 PIGMENTS - LIPOFUSCIN

• Wear & tear pigment

• Brownish-yellow granular
intracellular material that
accumulates in heart, liver &
brain with aging & atrophy
• Not injurious but an indication of
past free radical injury
• Causes brown atrophy
 PIGMENTS - MELANIN

• Brown-black pigment
synthesized by melanocytes in
epidermal layer of skin, protects
from harmful UV radiation
• Basal keratinocytes can cause
freckles as well as dermal
macrophages can cause abnormal
accumulation of the pigment
 PIGMENTS -HEMOSIDERIN

• Hemoglobin derived granular

pigment
• Golden yellow to brown in color
• Local/systemic excess of iron
• Iron is stored as ferritin micelles
in combination with apoferritin
protein
• Identified as prussian blue
histochemical reaction
 PIGMENTS - HEMOSIDERIN

• Hemosiderin accumulation is
usually pathologic but small
amount of pigment are located in
bone marrow, spleen, liver &
aging red cells
• Excessive accumulation of
hemosiderin is called
hemasiderosis
 PATHOLOGIC CALCIFICATION

• Pathologic calcification, a common process in a wide variety of

disease states, is the result of an abnormal deposition of calcium salts,
together with smaller amounts of iron, magnesium, and other minerals
• It takes two forms:
1. Dystrophic calcification
2. Metatastic calcification
 DYSTROPHIC CALCIFICATION

• Calcium metabolism is normal but it stores in injured tissue such as

necrotic areas
• Occurs in advanced atherosclerosis
• Can cause valva deformities
• Dystrophic calcification of aortic valves is prime cause for aortic
stenosis
• Extracellular deposition of crystalline calcium phosphate in vesicles,
these crystals from larger deposits
MITRAL STENOSIS
 METASTATIC CALCIFICATION

• Associated with hypercalcemia

• Occurs in healthy tissues
Main causes of hypercalcemia
Increased secretion of Parathyroid hormone
Bone destruction
Vitamin D disorders
Renal failure
METATASTIC CALCIFICATION
DIFFERENCE BETWEEN TYPES OF
CALCIFICATION