Intracellular Accumulations Flashcards
What is intracellular accumulation ?
Presence of abnormal amount of various substances
Substances Characteristics:
- They may be harmless or may cause injury
- They may be endogenous or be exogenous.
NOTE: endogenous: synthesised within the affected cells
Exogenous : produced elsewhere
Where does accumulation happen at a cellular level ?
- Within Organelles ( mainly lysosomes )
- In the nucleus
- In the cytoplasm
Pathways by which accumulation occurs :
- Abnormal metabolism
- Proteins Mutations
- Lack of enzymes responsible for breaking down certain compounds
- Ingestion of indigestible material
Example of abnormal metabolism :
Fatty change , In the liver
Proteins Mutation
- Mutations causes alterations in protein folding and transport
- defective protein accumulation , in the cytoplasm
-e.x : alpha 1-anti trypsin deficiency
Lacking of enzymes that are responsible for breaking down certain compounds
- Substrate accumulation , In the lysosome
- e.x : lysosomal storage diseases
Ingestion of indigestible materials
Carbon and silica accumulation
Fatty change Names :
Fatty change = steatosis = Fatty metamorphosis
What is steatosis?
Abnormal accumulation of triglycerides within parenchymal cells
How does steatosis occur ?
Defects at any step of uptake , catabolism and secretion ( from FA entry to lipoprotein exit )
What are these steps ?
- Free FAs from either adipose tissue or nutrition
- Transportation to hepatocytes
- Either : oxidation to form Ketones
Estrification to form triglycerides
Phospholipids and cholesterol - Triglycerides bind with apo-protein to form lipoprotein that can be transported within the circulation
Where fatty accumulation occurs mainly at organs level ?
1.liver 2. Heart 3. Skeletal muscles 4. Kidney
Why does fatty accumulation happen ? ( Cases )
Alcohol abuse , protein malnutrition , starvation , obesity , Diabetes mellitus , anaemia , anoxia and toxins
CCl4 and protein malnutrition :
Decrease the synthesis of apo-protein
Anoxia
Inhibits FA oxidation
Starvation
Increase Fatty acid metabolism from peripheral sources
Intracellular fatty accumulation severity effects : ( Mild , Moderate , Severe )
Mild accumulation : it has no effect on the cellular function
Severe accumulation : it may precede cell death
Moderate ( vital intracellular processes are NOT irreversibly impaired ) : it may transiently impair cellular function ……….. e.x : CCl4 poisoning
Effects of fatty change depend on :
- The cause of accumulation
- Severity of accumulation
Gross appearance of fatty change in the liver
- Mild accumulation : Has no effect in the gross appearance
- Severe accumulation : Liver apppears bright yellow , soft , greasy and enlarges ( reaches 3-6 kg weight )
Microscopic appearance of fatty change in the liver :
-Mild situation : small fatty vacuoles in the cytoplasm around the nucleus
-Severe situation : these vacuoles unite together and displace the nucleus to the periphery
Gross appearance of Mild fatty change in the heart :
- caused by prolonged moderate hypoxia as in severe anaemia
- focal intracellular fat deposits and trigger-like , tabby -cat pattern appearance ( specialised for the heart )
Gross appearance of severe fatty change in the heart :
- caused by : A) More Severe hypoxia
B) toxic myocarditis as diphtheria infection - diffuse fatty change ( occupancy of excess fats )
Cholesterol and cholesterol esters accumulation concept : (what is it ? )
Phagocytic Macrophages in contact with the lipid debris of necrotic cells may be stuffed with lipids ( cholesterol ) leading to foam appearance ( foam cells )
Cholesterol metabolism Normally
It is tightly regulated process
Why is cholesterol metabolism tightly regulated?
To ensure cell membrane synthesis without significant intracellular accumulation
Cholesterol accumulation examples
- Atherosclerosis
- Hereditary or acquired hyperlipidemic syndrome
- Xanthomas
Atherosclerosis
-smooth muscle cells and macrophages are filled with cholesterol vacuoles
- atherosclerotic plaques appears yellow in colour
Hyperlipidemic Syndrome
Macrophages accumulates intracellular cholesterol in the skin
Xanthomas
Macrophages accumulates intracellular cholesterol in tendons ( mass name is Xanthomas )
Protein accumulation examples :
- Nephrotic syndrome
- Russell bodies
- Alcoholic hyaline or Mallory bodies in alcoholic liver disease
Nephrotic Syndrome
- characterised by proteinuria
( heavy protein leakage across the glomerular filter )
-increased pinocytic reabsorption of proteins resulting in hyaline or pink appearance cytoplasmic droplets in the renal tubular epithelium
Nephrotic syndrome is ………….. meaning that ………
Reversible , proteinuria ends , the droplets disappears
Russell bodies
Accumulations of synthesised immunoglobulins in the RER in the plasma cells
Mallory bodies or alcoholic hyaline
They are eosinophilic , intracytoplasmic lesions composed of aggregated intermediate filaments that resist degradation
Why does glycogen accumulate within cells ?
Abnormalities in the metabolism of glucose or glycogen
Glycogen accumulation found in : (Cases )
1.poorly controlled DM
2. Glycogen storage disorders or glycogenosis due to genetic disorders
Glycogen accumulation sites in DM
- Renal tubular epithelium
- Cardiac myocytes
3.beta cells of the islets of langerhan
Glycogen storage disorders
Enzymatic defects in synthesis or break down of glycogen
Resulting in massive accumulation of glycogen with secondary injury and cell death
What are pigments ?
They are coloured substances that me be endogenous or exogenous
Exogenous pigment
Carbon ( Coal Dust )
Carbon as a pigment leads to
Anthracosis without affecting the cellular function and then may cause pneumoconiosis ( coal dust workers disease )
How does anthracosis happen ?
1.Carbon inhalation
2. Carbon phagocytosis by alveolar macrophages
3.Carbon transportation to the regional lymph nodes through lymphatic channels
4. Carbon aggregation
5. Blacken the draining lymph nodes and pulmonary parenchyma
How does pneumoconiosis happen?
1.Anthracosis
2. Heavy accumulation of Carbon
3. Fibroblast reaction
Endogenous pigments
1.lipofuscin
2.melanin
3.hemosiderin
Lipofuscin
- wear and tear pigment
- brownish- yellow
- liver , brain and heart
- by aging mainly
- e.x : brown atrophy of the heart
Melanin
- produced by melanocytes in the epidermis layer of the skin
- brownish black pigment
- acts as endogenous screen against harmful UV radiation
Hemosidrin
-hemoglobin - derived pigment
- caused by excess of iron locally or systemically
- local excess of iron occurs due to bruise ( haemorrhage in the skin )
- it produces golden yellow to brown colour
What is hemosiderosis ?
It is a condition characterised by systemic overload of iron with hemosiderin deposition .
Where does hemosiderosis starts ?
Firstly , mononuclear phagocyte in the liver , bone marrow , spleen and lymph nodes
Where does hemosiderosis spread later on ?
Parenchymal cells in the body mainly in the liver , heart , pancreas .
What triggers hemosiderosis :
- Increased absorption of dietary iron
- Haemolytic anaemias
- Blood transfusion
- Trauma
Increased absorption of dietary iron :
- it is the concept of hereditary hemochromatosis
Hereditary hemochromatosis :
- Inborn errors of metabolism
- Excessive absorption of iron from intestines
- Extensive accumulation of iron in tissues
- Causes : A) liver cirrhosis B) heart failure C) DM
Frequent blood transfusion :
RBCs with exogenous load of iron
Trauma = localised hemosiderosis
- found in : hands, feet , trunk or face
- caused by local haemorrhage under the skin
- brownish —> bluish —> yellowish
Hemosiderosis detection :
Prussian blue Reaction ( Perl’s solution and deep blue colour )
If it is stained in the blue colour , this conforms the presence of hemosiderosis…
What is pathologic calcification in general ?
Abnormal deposition of calcium salts in tissues
Pathologic calcification is classified into :
- Destrophic calcification
- Metastatic calcification
What is destrophic clacification ?
Calcium salts deposition in necrotic tissue with normal calcium level in blood
What is metastatic calcification ?
Calcium salts deposition in normal tissue due to increased calcium levels in blood ( hypercalcemia )
Why does destrophic calcification occur?
- TB caseous necrosis
- Atheromas of advanced atherosclerosis ( extremely common )
- Calcific aortic valve in the elderly
4.Carcinoma of the breast
Why does metastatic calcification occur ?
- Inreased secretion of parathyroid hormone
- Bone destruction
- Vit-D related disorders
- Renal failure
Cases involve bone destruction :
- Immobilisation
- Tumors as in myeloma , leukaemia , diffuse skeletal metastases
Renal failure and metastatic calcification:
Phosphate retention leading to secondary hyperthyroidism
How does destrophic calcification appear grossly ?
- Fine , white granules or clumps
- felt gritty or or stony hard
Does dystrophic calcification resemble metastatic calcification ? And How?
YES , they affect the interstitial tissues of the blood vessels , kidneys , lung and gastric mucosa
