Cell injury (Intracellular Accumulations // Pigments // Pathologic Calcification // Cell Aging) Flashcards
Decsribe Intracellular Accumulation ?
Accumulation of substances in abnormal quantities inside the cell : cytoplasm (esp: Lysosomes) or nucleus.
Mild IA => reversible cell injury
Severe IA => irreversible cell injury.
Types of Intracellular Accumulation substances ?
- Lipids
Triglycerides (Fatty change)
Cholestrol and cholestryl ester - Proteins
- Glycogen
- Pigment
Abnormal IA can be divided into 3 gp. EXPLAIN
1. Excessive Accumulation of normal cell constituents : **
Lipids (FA, Cholestrol) // Proteins // CARBS.
2. Accumulation of abnormal subsatnces produced by abnormal meatbolsim due to lack of enzymes **: storage disease // inborn errors of metabolism.
**3. **Accumulation of pigments : endogenous (under certain conditions) OR Exogenous (due to lack of enzymatic mechanisms to degrade them or to transport them to other sites )
Describe FC (Fatty change) or steatosis
Accumulation of neutral fat (triglycerides) inside the cytoplasm of the parenchymal cells.
Commonest site is liver but it also can happen in heart, kidneys, skeletal muscle.
What’s a Fatty Liver (FL) ?
Its causes ?
accumulation of fat in liver as it plays important role in fat metabolism.
Causes:
- Hyperlipidemia : fat entering liver cells exceeds the capacity of liver to metabolize it. As in diabetes mellitus, Obesity, congenital Hyperlipidemia.
- Alcohol (most common)
- Starvation : Protein calorie malnutrition
- Chronic illiness : Tuberclosis => endogenous toxin
- Hypoxia : anemia // congenital Heart failure
- Drusg : steroids // methotrexate.
- Hepatotoxins : Carbon Tetrachloride => exogenous toxin.
Lipids enter the liver cell from ………. or ………….
Diet // Adipose tissue (lipolysis)
What can cause a defect in fat metabolsim leading to a fatty liver ?
- Increase FA entering Liver
- Increase synthesis of FA by the liver
- Decreased oxidation of FA into ketone bodies => more esterification of FA into triglycerides.
- Decrease in alpha-Glycerophosphate => decrease esterification of FA into triglycerides.
- Decrease synthesis of Lipid Acceptor Protein => decrease in convertion of triglycerides into lipoprotein.
- Blocking excecretion of Lipoprotein out into the circulation.
How does the liver normally metabolzie the fat ?
- Normally, as FA enter the liver cell, most of it will be esterified into triglycerides & few will change into cholestrol, Ketone bodies and phospholipids.
- Intracellular triglycerides will be converted into lipoprotein reuiring the lipid acceptor protein.
- Excecretion of lipoprotein into the circulation as Plamsa Lipoprotein (LDL, VLDL)
Liver cell damage occurs when ……………..
Fat cannot be metabolized in it.
In most FL, It’s one of the mechanisms that occur but in ……………….., it’s all factors.
liver injury by chronic Alcoholism
What are morphologic features of FL ?
Grossly:
- Enlargment in liver, soft, tense glitering capsule.
- Pale Yellowish and greasy to touch.
Microscopically
- In H & E stain following paraffin technique shows the fat as unstained vacuoles in cytoplasm of hepatocytes as fat is dissolved in alcohol.
- Initially, fat vacuoles are small and present around the nucleus (Microvesicular).
- W/ progression of process, Vacuoles become large pushing the nucleus to the periphery of the cell to be flattened giving the ring appearance. (Macrovesicluar).
- Hepatocytes laden w/ large fat vacuoles may rupture causing these vacuoles to coalesce forming fatty cysts.
- Then, lipogranulomas appear consisitng of collection of lymphocytes, macrophages & some multinucleated giant cells.
What special stains to use to more observe fat ?
- Sudan dyes (III, IV, sudan Black).
- Oil red O
- Osmic acid
How does the body regulate cholestrol amount to prevent its accumulation ?
What happens to be accumulated ?
- Most cells use it to synthesize their cell memb.
- However, under certain pathological conditions, Phagocytic cells filled w/ lipids change into foam cells.
- Pathological conditions as :
* Sites of old hermorrages & infarcts : cholestrol is derived from broken RBCs & dead cells.
* Accumulation of cholestrol in tunica intima in arteries in case of atherosclerosis.
- Excess Accumulation of proteins appear in cytoplasm of cell as ………..
- I w conditions ?
- Eosinophilic cytoplasmic droplets.
- This can occurs in :
A. Kidney disorder resulting in heavy protein filtration (Proteinuria) : pinocytosis increases & fuse w/ lysosomes forming pink (eosinophilic) hyaline cytoplasmic droplets in epithelium of proximal convoluted tubule.
B. Rhinoscleroma : Accumulation of newly synthesized IG in rER in plasma cells cytoplasm as round eosinophilic => Russel bodies
What can cause Glycogen accumulation ?
AND Where ?
- As in Glycogen stroage disease, the lack of enzymes => abnormal glycogen metabolism=> its accumulation.
- In Cardiac M. Fibers, Skeletal M. Fibers, Liver cells w/ secondry tissue injury.
What are pigments ?
Colored substances that are either endogenous or exogenous.
Endogenous as : Melanin, Haemoprotein derived pigment (Haemosedrin), Lipofuscin.
Exgenous as : Inhaled pig. (Carbon) // Injected pig (Tattowing)
Describe the melanin ?
Brown-black pigment present in Hair, Skin, choroid od eye, Adrenal medulla, meninges.
What are Melanin pigmentation disorders ?
I. Hyperpigmentation
-
Generalized :
- Addison’s disease due to increase in MSH (melanin stimulating hormone) & ACTH (Adrenocorticotropic Hormone).
- Chloasma during pregnancy, in face / nipples genitalia => as stimulation of melanocytes by female sex hormones : estrogen & Progestrone => more melanin release.
2. localized :
- Freckles : brown skin patches in sun exposed areas.
- Melanotic tumors : Benign as pigmented nevi, and malignant melanoma due to increase melanogenesis.
II. Hypopigmentation :
-
Generalized :
Albinism : tyrosinase activity of melanocytes is genetically defective => no melanin is produced. -
Localized :
- Vitiligo
- Leprosy : as wound healing
What can cause excessive Haemosedrin storage ?
Increase in RBCs Breakdown or systemic iron overload.
Iron is stored in the tissues in 2 froms : ………. & ………..
Describe each form ?
- Ferritin & Haemosedrin.
- Discription :
I. Ferritin :
- is iron attached to apoferritin.
- Soluble
- NO LM, ONLY EM.
II. Haemosedrin :
- Aggregation of Ferritin.
- Identified by LM as golden yellow to brown granular pigments.
- Normal amounts can be found within mononucleated phagocytes in Liver, spleen, bone marrow where RBCs breakdown taked place.
- Insoluble.
- Special Stain : Perl’s or Prussian Blue Reaction => deep blue granules.
Haemosedrin Accumulation can cause : ……. & ……
Haemosidrosis & Haemochromatosis
Describe Haemosidrosis
def // types
- Deposition of hemosedrin in mononuclear phagocytes w/o causing tissue injury.
=> Localized : - Caused by hemorrhage in tissue => breakdown of RBCs => HB degraded and stored in Macrophage as Haemosedrin.
- EX : IN Chronic Pulmonary Venous Congestion : we can find **Brown induration **resulting from small hemorrhages. & Heart Failure cells w are Haemosedrin-laden alveolar MQ.
-
=> Generalized :
Caused by systemic iron overload due to : - Reapeated blodd transfusion or parenteral iro therapy.
- Chronic Haemolytic Anemia as Thalassemia.
- Excessive dietary intake of iron.
Describe Haemochromatosis ?
=> Progressive & more extensive accumulation of Haemosedrin in parenchymal cells throughout the body esp. in Liver, pancreas, heart, endocrine glands with tissue injury.
=> Primary (hereditary)
- caused by excessive intestinal absorption of iron even when the amount taken is normal.
- Autosomal dominant disease ccc by a triad : pigmented liver cirrhosis & pancreas damage => diabetes mellitus & bronze colored skin pigmentation (bronze diabetes)
=> Secondary (Acquired)
- Long term of generalized Haemosiderosis.
Describe Lipofuscin ?
Color, Site
- Yellow to brown intracellular lipid pigm.
- Found in atrophic cells => “wear & tear pig).
- Sites : Myocardial fibers (brown atrophy of Heart) / hepatocytes / neurons / Leydig cells in testis.
