9. Cellular Pathology 4: Autophagy, Intracellular Accumulations and Calcifications
A 38-year-old man has a health screening examination. He has a routine chest x-ray that shows a 2 cm nodule in the right lower lobe. The nodule has focal calcifications. A wedge resection of the nodule is done. On microscopic examination the nodule shows caseous necrosis and calcification. Which of the following processes explains the appearance of the calcium deposition? A. Dystrophic calcification B. Apoptosis C. Hypercalcemia D. Metastatic calcification E. Excessive ingestion of calcium
A. dystrophic calcification because "caseous necrosis and calcification"
Microtubular Abnormalities: - What condition is associated with defective neutrophil movement?
Chediak-Higashi syndrome
Microtubular Abnormalities: - immobilization of cilia of the respiratory tract can lead to BRONCHIECTASIS in what syndrome?
Kartagener's syndrome
Fatty Change: (Steatosis) - Decreased protein intake in diet causes decreased synthesis of apolipoproteins. ___ is another cause of fatty change
Kwashiorkor
Examples of Intermediate Filament Defects: - Ubiquitenated NEUROFILAMENTS from degenerated substantia nigra neurons?
Lewy bodies
Fatty Change: (Steatosis) - What organs are affected?
Liver (most common) heart muscles kidneys
Chediak-Higashi and Kartagener's syndrome involves?
MICROTUBULES
Metastatic Calcification: - Patient with hyperparathyroidism has calcification of tubular basement membrane of the nephron?
Nephroncalcinosis
Examples of Intermediate Filament Defects: - Ubiquitenated NEUROFILAMENTS in brain as seen in old age or Alzheimer's disease?
Neurofibrillary tangle
Hemosiderosis: - Hemosiderosis is the accumulation of hemosiderin within macrophages. Does it cause associated tissue or organ damage?
No hemosiderosis = no damage
Hyaline Change: - Can be intracellular or extracellular. Russel bodies, Mallory alcoholic hyaline PAS positive globules in periportal hepatocytes These are all?
intracellular hyaline
Autophagy: 1.What is sequestered in an autophagic vacuole?
intracellular organelles cytosol
Hyaline Change: - Mallory bodies (alcoholic hyaline) are masses of what filaments within hepatocytes?
keratin intermediate filaments note the eosinophilic masses
Cholesterolosis - is the accumulation of cholesterol laden MACROPHAGES where?
lamina propria of Gall Bladder
Pigment Accumulations: - ____ - is a LIPOCHROME (wear and tear or aging pigment), undigestible, non injurious to the cell, yellow brown and finely granular morphology, peri-nuclear
lipofuscin
Pigment Accumulations: - lipofuscin is seen in what organs of aging patients, malnutrition patients or cancer cachexia?
liver heart
What are the two types of hemosiderosis?
local systemic
What type of hemosiderosis consists of deposition that results from hemorrhage into tissues such as in pulmonary congestion (leftheart failure)?
local hemosiderosis
Autophagy: 2. Autophagic vacuoles with organelles and cytosol then fuse with?
lysosome
Examples of Intermediate Filament Defects: - KERATIN FILAMENTS seen in hepatocytes of alcoholics, and is a microscopic feature of alcoholic hepatitis?
mallory bodies
Examples of Intermediate Filament Defects?
mallory bodies lewy bodies neurofibrillary tangles
Hyaline Change: - What intracellular hyaline is seen in alcoholic liver disease?
mallory bodies (alcoholic hyaline)
Cytoskeletal Abnormalities: - What happens to proteins that are ubiquitenated?
marked for destruction
Pigment Accumulations: - ___ - endogenous brown-black pigment formed when TYROSINASE catalyzes ox. of tyrosine into dihydrophenylalanine
melanin tyrosine --> (tyrosinase)-->dihydrophenylalanine
___ ___ - deposition of calcium in normal and undamaged healthy tissue
metastatic calcification
Cytoskeletal Abnormalities: - What is composed of tubulin?
microtubules
Cholesteatoma is a collection of cholesterol in what structure that leads to hearing loss?
middle ear
Intracellular accumulations: - water, lipids, proteins and carbohydrates accumulate inside the cell. what are these?
normal cellular constituents
Metastatic Calcification: - Calcification of the basal ganglia can occur due to high levels of ____
phosphorous
Hyaline Change: - most commonly occurs due to accumulation of ___
proteins
Hypercalcemia: - Vitamin D intoxication leads to or related disorders can cause hypercalcemia how?
unable to process calcium
Metastatic Calcification: - due to an increase in serum ____
calcium hypercalcemia
Dystrophic Calcification: - Morphology on microscopy
calcium salts have basophilic appearance
Cytoskeletal Abnormalities: - What aids in proper protein folding?
chaperon
Lipid Accumulations: - What lipid accumulation is responsible for atherosclerosis, Xanthomas, Cholesterolosis, Niemann pick disease type c?
cholesterol
Fatty Change: (Steatosis) - Cue to increased NADH in the body after alcohol use, synthesis of ___ _ __ is increased.
glycerol 3 phosphate
Fatty Change: (Steatosis) - what does PAS stain magenta?
glycogen
Dystrophic Calcification: - Patients with tuberculosis or histoplasmosis patients can also have calcifications known as?
granulomas
____ - accumulation of hemosiderin within parenchymal call WITH tissue damage and organ dysfunction
hemochromatosis
Pigment Accumulations: - ___ - is an iron containing pigment found in macrophages that appears golden yellow to brown on H&E, identified by PRUSSIAN BLUE STAIN
hemosiderin
While in a home improvement center warehouse buying paint, a 35year-old man hears 'Look out below!' and is then struck on the leg by a falling pallet rack, which strikes him on his left leg in the region of his thigh. The skin is not broken. Within 2 days there is a 5 x 7 cm purple color to the site of injury. Which of the following substances has most likely accumulated at the site of injury to produce a yellow-brown color at the site of injury 16 days later? A. Lipofuscin B. Bilirubin C. Melanin D. Hemosiderin E. Glycogen
hemosiderin
Hyaline Change: - Patients with hypertension or DM will suffer from what extra-cellular hyaline in small vessels?
hyaline arteriosclerosis
____ change - nonspecific term used to describe intracellular or extraceullar accumulation which has a PINK homogenous appearance?
hyaline change
Hyaline Change: - What extracellular hyaline will affect the lungs of babies?
hyaline membrane disease of the newborn notice lung section
Hypercalcemia: - can cause renal failure by increasing?
hypercalcemia --> hyperphosphatemia --> renal failure see kidney pic
Hypercalcemia: - pt with primary parathyroidism suffers from hyperplasia and adenoma. What is the cause of hypercalcemia?
increased PTH
Hypercalcemia: - Causes?
increased PTH destruction of bone Vitamin D related disorders Milk and antacid abuse
Cytoskeletal Abnormalities: - what filaments are important in integration of cell organelles and examples are: keratin, vimentin, desmin, neurofilaments, glial filaments?
intermediate filaments
Intracellular accumulations: - Accumulations of abnormal amounts of substances occur within cells. What are the three categories of substances?
1. normal cellular constituents 2. pigments 3. abnormal substances
Pigment Accumulations: - Carbon/coal dust is an anthracotic pigment what can be inhaled via AIR POLLUTION. Inhalation leads to accumulation by alveolar macrophages in lymphatics, lymph nodes and lungs. A patient presents with black coloration. What is the condition described?
Anthracosis
An 84-year-old man dies from complications of Alzheimer disease. At autopsy, his heart is small (250 gm) and dark brown on sectioning. Microscopically, there is light brown perinuclear pigment with H&E staining of the cardiac muscle fibers. Which of the following substances is most likely increased in the myocardial fibers to produce this appearance of his heart? 20% 20% A. Hemosiderin from iron overload B. Lipochrome from 'wear and tear' C. Glycogen from a storage disease D. Cholesterol from atherosclerosis E. Calcium deposition following necrosis
B. aging patient with lipofuscin accumulations in the heart, peri-nuclear
A patient presents with: cirrhosis diabetes mellitus skin pigmentation hereditary hemochromatosis due to HFE gene mutation. What condition is this?
BRONZE DIABETES
Fatty Change: (Steatosis) - A patient that works in the cleaning industry presents with a "fatty liver" what would be the cause?
CCl4
Pigment Accumulations: - Coal miners can accumulate dust which induseas FIBROBLASTIC reactions that lead to LUNG DISEASE. What do these patients have?
COAL WORKER'S PNEUMOCONIOSIS
Dystrophic Calcification: - Dystrophic calcification on the mitral valve indicates?
Calcific mitral stenosis
A 49-year-old man with a history of alcohol abuse has increasing abdominal girth. On examination his liver edge is firm. A liver biopsy shows cirrhosis, and individual hepatocytes contain red, globular inclusions positive for cytokeratin with immunohistochemical staining. Which of the following structural elements are these intracellular globules most likely to contain? A. Actin and myosin B. Cholesterol esters C. Fatty acids D. Fibronectin E. Intermediate filaments F. Microtubules
E. intermediate filaments mallory bodies in pt with alcoholic hepatitis --> keratin intermediate filaments
Dystrophic Calcification: - Dystrophic calcification visible on X-rays indicates?
Enzymatic Fat Necrosis
Cytoskeletal Abnormalities: - What chaperon marks abnormal proteins for degradation?
Heat Shock Protein (ex. ubiquitin)
What is caused by the mulation in HFE gene, and leads to hemosiderin deposition and organ damage in liver?
Hereditary hemochromatosis
Hemochromatosis types?
Hereditary hemochromatosis Secondary hemochromatosis
Hyaline Change: - what intracellular hyaline is involved in alpha-1-antitrypsin deficiency?
PAS positive globules in periportal hepatocytes
Hypercalcemia: - Squamous cell carcinoma of the lung can be ectopic and cause hypercalcemia how?
PTH related protein secretion
Examples of Intermediate Filament Defects: - Lewy bodies are ubiquitenated NEUROFILAMENTS seen in what disease?
Parkinson's disease
___ ___ - the abnormal deposition of calcium in tissues?
Pathologic calcification
Dystrophic Calcification: - ___ ___ - a single calcified cell may acquire outer layers of calcium giving rise to these bodies
Psammoma bodies
Cholesterol: - cells use cholesterol for membrane synthesis. Accumulation of cholesterol is seen in many pathological conditions?
atherosclerosis xanthomas cholersterolosis cholesteatoma nieman pick disease type c
Dystrophic Calcification: - Deposition of cholesterol can lead to plaques, and superimposed calcium deposition can occur in?
atherosclerotic plaques
Hyaline Change: - What intracellular hyaline is seen inside plasma cells due to excess immunoglobulin accumulation in RER which fuse to form eosinophilic globules?
Russel bodies
What is hemochromatosis is caused by multiple blood transfusions, as in patients with beta thalassemia major?
Secondary hemochromatosis
Fatty Change: (Steatosis) - To rule out water and glycogen accumulation in a liver microscopy stain, What kind of stains can be performed? How does lipid stain?
Sudan IV and Oil Red O PAS
____ ____ - double membrane bound vacioles in which cytoplasmic materials, including organelles are sequestered and degraded following fusion of vesicles with lysosomes
autophagic vacuoles
_____ - process in which a cell "eats" its own contents
autophagy
____ - tumor like masses composed of clusters of MACROPHAGES (foamy cells) containing cholesterol
Xanthomas
Intracellular accumulations: - Exogenous minerals and endogenous products of abnormal metabolism accumulate. What are these considered?
abnormal substances
Cytoskeletal Abnormalities: - What filaments are involved in contractile processes?
actin
Causes of Fatty Change: - What is the most common cause of fatty change in the liver?
alcohol
Hyaline Change: - What extracellular hyaline is present in multiple organs?
amyloid
Dystrophic Calcification: - Dystrophic calcification in the BICUSPID aortic valve?
aortic stenosis
Fatty Change: (Steatosis) - Alcohol use also decreases the process of __ ___ of fatty acids, thus fatty acids accumulate
beta-oxidation
Hypercalcemia: - Multiple myeloma, breast cancer and Paget's disease all cause hyperglycemia in what way?
bone destruction
A 12-year-old boy has had multiple episodes of ear pain accompanied by fever. On examination his right tympanic membrane is red and bulging with yellow exudate. Laboratory studies of the exudate show culture positive for Hemophilus influenzae. A year later he has conductive hearing loss on the right, and a head CT scan shows a mass in the right middle ear. Which of the following materials is most likely to be seen in the tissue curetted from his middle ear? A. Lipofuscin pigment B. Russell bodies C. Neutrophil granules D. Cholesterol crystals E. Anthracotic pigment
d. cholesterol crystals
Pigment Accumulations: - Tattooing is localized pigmentation of skin which is phagocytosed by what cells?
dermal macrophages
Autophagy: 3. Lysosomal enzymes are released into the autophagic vacuole. What happens?
digestion of cellular components
Pathologic Calcification: __ ___ - occurs in DEAD, DYING and NECROTIC tissues, associated with damaged HEART VALVES,
dystrophic calcification
Pathologic Calcification: two forms?
dystrophic calcification metastatic calcification
Pigment Accumulations: - such as lipofuscin, melanin and hemosiderin are synthesized within the body and are ____.
endogeneous
Fatty Change: (Steatosis) - Gross morphology?
enlarged liver with yellow discoloration
Hyaline Change: - Hyalime arteriosclerosis - arterioles present with a glassy, amorphous appearing ____ colored material on the vessel wall.
eosinophilic notice eosinophilic material on vessel wall
Pigment Accumulations: - Pigment accumulations from carbon/coal dust or tattoo ink come from outside the body, and are considered ____.
exogenous
Hyaline Change: - Can be intracellular or extracellular. Hyaline arteriosclerosis Amyloid Hyaline membrane disease of newborn these are all?
extracellular hyaline
Fatty Change: (Steatosis) - what does Sudan IV and oil red O stain orange?
fat
Fatty Change: (Steatosis) - After alcohol use, there is an increased amount of acetyl coA, which increases synthesis of?
fatty acids
___ ___ (____) - is the abnormal accumulation of TRIGLYCERIDES in parenchymal cells, due to the imbalance among uptake, utilization and secretion of FAT
fatty change (Steatosis)
Fatty Change: (Steatosis) - In microscopy, the liver presents with nucleus pushed to the periphery and single or multiple fat droplets fuse to form?
fatty cysts
Pigment Accumulations: - Hemosiderin consists of aggregates of ____
ferritin
Pigment Accumulations: - Lipofuscin is a sign of __ ___ injury and __ ___
free radical injury lipid peroxidation
Fatty Change: (Steatosis) - During a state of ____, there is increased mobilization of fatty acids from adipose tissue which causes a fatty change.
starvation
Xanthomas occur in what connective tissues?
sub-epithelial connective tissues tendons
What type of hemosiderosis is generalized deposition that occus from blood transfusions, excessive Fe intake or hemolysis?
systemic hemosiderosis
Dystrophic Calcification: - Psammoma bodies are indicative of which cancers involved with calcium deposition?
thyroid cancer ovarian cancer
Lipid Accumulations: - What lipid accumualtion is responsible for the fatty change?
triglycerides
Lipid Accumulations: - What kind of lipid accumulations occur within the cell?
triglycerides cholesterol