GenPath - Autophagy - PL

Refers to lysosomal digestion of the cell's own components

Autophagy

⭐ A survival mechanism in times of nutrient deprivation

Autophagy

Also involved in the clearance of misfolded protein.

Autophagy

might result in the accumulation of misfolded proteins that can cause neuro-degenerative diseases.

Defective autophagy

In autophagy, Intracellular organelles and portions of the cytosol are sequestered within an

autophagic vacuole

The autophagic vacuole fuses with a lysosome forming an

autophagolysosome

breakdown the cellular components

lysosomal enzymes

Targeted proteins are translocated across the lysosomal membrane in a complex with chaperone proteins (such as Hsc-70) that are recognized by the lysosomal membrane receptor lysosomal-associated membrane protein 2A (LAMP-2A), resulting in their

unfolding and degradation.

Chaperone-mediated autophagy (СМА)

By Invagination of the lysosome membrane, cytosolic components are directly taken up by the lysosome itself through.

Micro-autophagy

It could be selective or non-selective

Micro-autophagy

This is an area of active investigation, autophagy can both promote - growth and act as a defense against —.

Cancer

In ____, formation of autophagosomes is accelerated. (Neurodegenerative disorders)

Alzheimer disease

In ____, mutant protein huntingtin impairs autophagy. (Neurodegenerative disorders)

Huntington disease

Many pathogens are degraded by autophagy; these include mycobacteria, Shigella spp., and HSV-1.

This is one way by which microbial proteins are digested and delivered to antigen presentation pathways.

Infectious diseases

Macrophage-specific deletion of Atg5 increases susceptibility to

tuberculosis

Studies have linked both Crohn disease and ulcerative colitis to autophagy related genes.

Inflammatory bowel diseases

Cells may accumulate abnormal amounts of various substances

• Maybe harmless of maybe associated with varying degrees of injury.

Intracellular accumulations

⭐any abnormal accumulation of triglycerides within parenchymal cells

most often seen in the liver

may also occur in the heart, skeletal muscle, kidney, and other organs

caused by toxins, protein malnutrition, diabetes mellitus, obesity, and anoxia

alcohol abuse and diabetes are the most common causes of fatty liver in industrialized nations

Steatosis (Fatty Change)

much less common than lipid accumulations

occurs when excesses are presented in cells

or if the cells synthesize excessive amounts

Proteins

common exogenous pigment - carbon, a ubiquitous air pollutant of urban life.

when inhaled, are phagocytosed by

alveolar macrophages → lymphatic

channels to the tracheobronchial

lymph nodes.

Pigments

(Pigments) aggregates blacken the draining lymph nodes

accumulation of carbon in the lungs.

There's a black pigment in the lung tissues

anthracosis

an insoluble brownish-yellow granular intracellular material.

Lipofuscin

accumulates in a variety of tissues.

It represents complexes of lipid and protein that derive from the free-radical catalyzed peroxidation of polyunsaturated lipids.

Lipofuscin

(Lipofuscin) the brown pigment imparts an appearance to the tissue called

brown atrophy

Pale golden brown finely granular pigment in nearly all hepatocytes is

lipochrome (lipofuscin)

This is a "wear and tear" pigment from the accumulation of autophagolysosomes over time.

This pigment is of no real pathologic importance

Lipofuscin pigment

endogenous, non-hemoglobin derived, black-brown pigment synthesized by melanocytes in the epidermis

Melanin

acts as a screen against harmful ultraviolet radiation

Melanin

can also accumulate melanin, as in freckles, as well as dermal macrophages

keratinocytes

Adrenal glands not making enough aldosterone.

Addison's disease

It is caused by the stimulant effect of excess adrenocorticotrophic hormone (ACTH) on the melanocytes to produce melanin.

Addison's disease

is an acquired pigmentation, light-brown or dark brown, which appears and is accentuated by exposure to sunlight.

accumulation of pigment to certain parts of the body

Cloasma (melasma)

It can be associated with pregnancy, the use of oral contraceptives and other medicines, or alternatively without any apparent cause (idiopathic).

Cloasma (melasma)

These are light to dark brown pigmented birthmarks that commonly appear on a newborn's skin. Spots can change in size and number over time.

Café au lait spots

usually inherited as an autosomal dominant trait,

is the combination of skin hyperpigmentation and Peutz-Jeghers polyps in the gastrointestinal tract.

Peutz Jeghers Syndrome

The pigmentation consists of clusters of black-brown perianal and genial are the

Peutz Jeghers Syndrome

More than six café-au-lait spots can be a sign of an underlying genetic condition like

neurofibromatosis type 1 (NF 1).

The hyperpigmentation is caused by high levels of circulating

ACTH that bind to the melanocortin 1 receptor on the surface of dermal melanocytes.

Addison's disease

has long been considered as a harmless pigmentation of the colorectum associated with the use of laxatives containing anthraquinone.

Melanosis coli

affects the production of melanin, the pigment that colours skin, hair and eyes. It's a lifelong condition, but it does not get worse over time.

Albinism

People with _____ have a reduced amount of melanin, or no melanin at all. This can affect their colouring and their eyesight.

Albinism

was defined as either a small acquired isolated depigmented lesion without typical segmental distribution, or two to three small acquired lesions localized in a non-segmental area with a maximum of 5 cm.

Iris

small, scattered patches of depigmentation.

Focal vitiligo

People who have this type tend to see rapid color loss on one side of the body.

Segmental

hemoglobin derived granular pigment

golden-yellow to brown

accumulates in tissues when there is a local or systemic excess of iron

Hemosiderin

In hemosiderin, iron is normally stored in cells in association with the protein, apoferritin, forming

ferritin micelles

represents large aggregates of ferritin micelles

Hemosiderin pigment

Common process in a wide variety of disease states

implies the abnormal deposition of calcium salts, with small amounts of iron, magnesium, and other minerals.

Pathologic calcification

is the abnormal tissue deposition of calcium salts.

Pathologic calcification

The deposition occurs locally in dying tissues

It occurs despite normal serum levels of calcium and In the absence of derangements In calcium metabolism

Dystrophic Calcification

The doposition of caklum salts in otherwise normal tissues

It almost always results from hypercalcemia secondary to some disturbance in calcium metabollsm

Metastatic Calcification

Visible in atheromas of advanced atherosclerosis

* Aorta and large arteries, characterized by accumulation of lipids

Can also develop in aging or damaged heart valves

Dystrophic Calcification

(Dystrophic Calcification) ultimate end product of pathogenesis is the formation of

crystalline calcium phosphate

have been linked to increased risk of cancers, heart disease, dementia and mortality.

Shortened telomeres

is the result of a progressive decline in the life span and functional capacity of cells.

Cellular aging

This study is notable for showing a connection between a common form of psychological stress, phobic anxiety, and a plausible mechanism for premature aging.

Anxiety Linked to Shortened Telomeres, Accelerated Aging

⭐ In neurons, a defective autophagy might result in accumulation of misfolded proteins that can cause diseases.

neurodegenerative

⭐ A starved cell subsists by:

eating its own components

⭐During initiation of autophagy _ complexes that sense nutrient deprivation and eventually stimulate the formation of an autophagic vacuole.

multi-protein

⭐How autophagy is regulated and executed at the molecular level have been made in:

Yeast

⭐There are __ different autophagy related genes

32

⭐Which of the following types of autophagy is selective?

chaperone mediated

⭐Chaperone proteins are recognized by a lysosomal membrane receptor

LAMP 2A

⭐Microautophagy occurs by:

invagination of the lysosomal membrane

⭐Accumulated substance may be found in the cytoplasm, lysosomes and

nucleus

⭐When phagocytic cells may become overloaded with lipids

hypercholesterolemia

A hemoglobin-derived granular pigment accumulates in tissues when there is a local or systemic excess of iron

Hemosiderin

Major causes:

Increased secretion of parathyroid hormone

Destruction of bone

Vitamin-D related disorders, including vitamin-D intoxication and sarcoidosis

Renal failure, in which phosphate retention leads to secondary hyperparapthyroidism

Metastatic Calcification

local excess of iron and consequently of hemosiderin, result from

hemorrhage

The most common site of cholesterol accumulation is in the

Arteries

The iron can be unambiguously identified by the

Prussian blue histochemical reaction

is responsible for the stimulation which hyperactives the hormones for the production of the adrenaline

Pituitary gland (adrenal gland)