CELLULAR AND EXTRA-CELLULAR INJURIES AND DISORDERS
CELLULAR AND EXTRA-CELLULAR INJURIES AND DISORDERS
Types of Cellular Injuries
PROTEIC
Intracellular Hyaline degeneration
Granular/vacuolar (hydropic) degeneration
Extracellular
Hyaline degeneration
Amyloid degeneration
LIPIDIC
Simple lipids
Liver steatosis (fatty change)
Complex lipids (storage diseases)
Niemann Pick Disease
Gaucher Disease
PIGMENT DEPOSITS
Cholestasis (bile pigment)
Definition of Injuries
Pathologic processes caused by the general or local metabolism of specific substances or chemical products.
PROTEIC DEGENERATION
Granulovacuolar (Hydropic Degeneration)
Stages and Etiology:
Clear intumescence: Viral infections, acute intoxications
Granular degeneration (cloudy intumescence): Acute infections, burns, inanition
Vacuolar degeneration:
Affects renal tubule cells after IV hypertonic sucrose or in dioxan and diethylene glycol intoxications.
Results in decreased ATP and ability to utilize ATP leading to the Na/K pump failure, increasing intracellular water and electrolyte, causing hydration and increased cell volume.
Granular degeneration (reversible) < Vacuolar degeneration (irreversible)
Gross and Microscopy Features
Kidneys
Gross Features:
Weight and volume increase, distended capsule, pale opaque color
Cut surface appears moist and cloudy, comparable to "boiled meat" or "withered leaf".
Microscopic Features:
Granular degeneration: Cells enlarged, foamy, and granular cytoplasm with a conserved nucleus
Vacuolar degeneration: Pronounced cloudy aspect with a foamy appearance due to vacuole presence, cytoplasm retracts around clear spaces. Special stains for lipids are negative.
PROTEIC DEGENERATIONS
Hyaline Degeneration
Definition:
Irreversible process characterized by the deposition of acellular, dense, eosinophilic, homogeneous, translucent proteic material called hyaline.
More frequently found extracellular than intracellular.
Gross Features of Hyaline
White-pearly, translucent deposits with a glassy appearance similar to cake glaze.
Intracellular Hyaline
In Kidneys
Affects proximal convoluted tubules with Russell bodies in plasma cells leading to Nephrotic syndrome, where proteins reach the glomerular filtrate through pinocytosis.
Chronic inflammatory disease causes accumulation of monoclonal proteins inside the dilated cisterns of the endoplasmic reticulum in multiple myeloma.
Mallory-Denk Bodies
Seen in hepatocytes during chronic alcoholic hepatitis where intermediate filaments accumulate in the cytoplasm.
Reinke Crystals
Found in testes.
Crooke Inclusions
Found in basophilic cells from the hypophysis, appears physiologically in Leydig interstitial cells and is related to Cushing syndrome.
Extracellular Hyaline
Physiologic vs Pathologic
Pathologic
Corpus Albicans: Involution of the corpus luteum, producing white, fibrous scar tissue.
Keloid Scar: Hyalinization of the arterioles in hypertension and Diabetes Mellitus, with plasma proteins extravasating and depositing on the basal membrane. This results in:
In DM deposits found in glomerular capillaries, forming Kimmelstiel-Wilson nodules leading to nephrosclerosis and chronic renal disease.
Amyloid Proteic Degeneration
Extracellular Proteic Accumulations
Amyloid Definition:
Paraprotein formed by fibrillary proteins (95%) and a P component (non-fibrillar) (5%).
Functional disturbances occur without inflammatory reactions.
Special Stains for Amyloid
Gross Stains:
Virchow reaction with Lugol solution produces brown-mahogany staining; with sulfuric acid yields blue.
Microscopy Stains:
Congo Red shows red-orange tint and appears apple green birefringent under polarized light.
Other stains: Methyl violet, toluidine blue, Thioflavin T, and Van Gieson.
Types of Amyloidosis
Primary Amyloidosis: Associated with light chain amyloidosis, affects multiple systems including renal and cardiac.
Secondary Amyloidosis: Results from chronic infections/inflammatory diseases, involving AA protein synthesis in the liver (e.g., rheumatoid arthritis).
Hereditary Amyloidosis: Familial Mediterranean fever with characteristics of fever and serositis; amyloid polyneuropathy.
Localized Amyloidosis: Confined to one organ (e.g., senile cardimyopathy, Alzheimer's disease).
Renal Amyloidosis
Clinical Features
Extracellular accumulation of eosinophilic material leading to nephrotic syndrome (proteinuria, hypoalbuminemia, edema). Diagnosis via kidney biopsy.
Gross and Microscopic Features
Late stages show contracted kidneys with rough, pale, waxy cut surface.
Glomerular Involvement: Thickening of the basement membrane and distortion of glomerular capillary tufts.
Splenic Amyloidosis
Types
Sago Spleen: Enlarged with translucent, waxy nodules resembling tapioca; amyloid deposits in white pulp arteriolar walls.
Lardaceous Spleen: Marked splenomegaly with cut surfaces showing amyloid areas, involving small arteries and connective tissues within the organ.
Cholestasis
Pigment Deposits
Cholestasis refers to the bile pigment accumulation into biliary canaliculi, causing distension and a brown-green pigment filling.
Bio characteristics include hyperbilirubinemia and increased serum alkaline phosphatase levels leading to clinical symptoms of jaundice, pruritus, and xanthomas.
Causes of Jaundice
Increased bilirubin production due to excessive RBC destruction (unconjugated hyperbilirubinemia).
Defect in bilirubin handling due to hepatocellular injury (biphasic jaundice).
Impaired bilirubin transport in biliary system (conjugated hyperbilirubinemia).
Gross and Microscopic Features of Cholestasis
Features include distended capsule, brownish-green color, and hard consistency; cut surface reveals dilated bile ducts with leaked bile. Pigment is seen in hepatocytes and Kupffer cells.
Lipidic Dystrophies
Steatosis
Steatosis denotes intracellular accumulation of simple lipids, predominantly triglycerides (TG), in non-adipocyte cells such as hepatocytes or myocytes.
Etiology includes alcohol consumption, malnutrition, poison intoxications, diabetes, hypoxia, and others.
Gross Features of Hepatic Steatosis
Microscopy: Volume increase in hepatic structure, friable parenchyma, yellow coloration; appears accentuated in lobular architecture and reveals different distributions based on etiology (e.g., alcoholic centrolobular steatosis).
Macroscopic Steatosis
Microvesicular steatosis characterized by intracytoplasmic vacuoles with perinuclear disposition leading to a ‘signet ring’ appearance.
Storage Diseases
Gaucher Disease
Definition: Autosomal recessive disease due to a deficiency of beta-glucosidase resulting in glucocerebroside accumulation in macrophages.
Symptoms include organomegaly, bone pain, and hematologic dysfunctions (anemia, leukopenia).
Types of Gaucher Disease
Type 1: Affects organs such as bone marrow, spleen, and liver, rarely CNS; onset in young adults/adolescents with reduced survival.
Type 2: Acute neuronopathic, onset in infancy with severe CNS lesions; survival limited to 2-4 years.
Type 3: Subacute neuronopathic, with neurologic symptoms and reduced survival beyond 30 years; onset in adolescence.
Microscopy Features of Gaucher Disease
Includes hepatomegaly and splenomegaly, nodular/diffuse infiltrate, and presence of macrophages with characteristic hyperchromatic nuclei and eosinophilic cytoplasm resembling crepe paper.
Niemann Pick Disease
Definition: Autosomal recessive disorder due to sphingomyelinase deficiency resulting in sphingomyelin accumulation in macrophage system.
Symptoms include hepatomegaly, splenomegaly, and neurologic dysfunctions.
Variants include types A, B, C, and D based on age of onset and involvement of CNS.
Comparison of Gaucher vs Niemann Pick Cells
Gaucher Cells: Larger macrophages with crumpled tissue paper-like cytoplasm.
Niemann Pick Cells: Smaller macrophages with foamy and vacuolated cytoplasm.