Intracellular accumulations

What are intracellular accumulations?

Abnormal buildup of substances in cells

What causes intracellular accumulations?

Cell stress and injury

Two categories of intracellular accumulations?

Normal and abnormal substances

Examples of normal accumulated substances?

Water, lipids, proteins, carbohydrates

Examples of abnormal substances?

Minerals and infectious products

First pathway of intracellular accumulation?

Defective metabolism and transport

Example of defective metabolism accumulation?

Fatty liver

Second pathway of intracellular accumulation?

Defective protein folding and transport

Example of protein folding defect?

α1-antitrypsin accumulation

Third pathway of intracellular accumulation?

Inherited enzyme deficiency

Example of inherited enzyme defect?

Glycogen storage disease

Fourth pathway of intracellular accumulation?

Inability to degrade exogenous material

Example of exogenous accumulation?

Anthracosis

Major intracellular accumulations?

Fat, pigments, proteins, glycogen, calcium

What is steatosis?

Triglyceride accumulation in cells

Most common organ affected by steatosis?

Liver

Other organs affected by steatosis?

Heart, muscle, kidney

Causes of fatty change?

Alcohol, diabetes, obesity, hypoxia

What does NASH stand for?

Nonalcoholic steatohepatitis

Gross appearance of fatty liver?

Yellow, soft, greasy

How large can fatty liver become?

2–4 times normal size

Which stains detect fat in tissue?

Oil Red O and Sudan IV

Color produced by Oil Red O stain?

Orange-red

What accumulates in fatty change?

Triglycerides

What is tigered heart?

Yellow streaked myocardium from hypoxia

What causes tigered heart?

Moderate hypoxia

What infection can cause fatty change in heart?

Diphtheria

What accumulates in atherosclerotic plaques?

Cholesterol esters

Which cells become foam cells in atherosclerosis?

Macrophages and smooth muscle cells

What are xanthomas?

Cholesterol-filled macrophage collections

What disease is caused by defective cholesterol trafficking?

Niemann-Pick disease type C

What is cholesterolosis?

Cholesterol-laden macrophages in gallbladder

Appearance of intracellular protein accumulations?

Eosinophilic droplets or aggregates

What causes renal protein reabsorption droplets?

Proteinuria

What disease shows neurofibrillary tangles?

Alzheimer disease

What are proteinopathies?

Protein aggregation diseases

What is hyaline change?

Glassy pink appearance in tissue

How does hyaline appear on H&E?

Homogeneous eosinophilic pink

What are pigments?

Colored substances in tissues

Two pigment categories?

Exogenous and endogenous

Examples of exogenous pigments?

Coal and silica

Examples of endogenous pigments?

Lipofuscin and hemosiderin

What is lipofuscin?

Wear-and-tear pigment

What causes lipofuscin accumulation?

Free radical injury

Composition of lipofuscin?

Lipid and protein

Color of lipofuscin?

Brown

Organs containing lipofuscin?

Heart, liver, brain

What does lipofuscin indicate?

Previous free radical damage

What is melanin?

Brown-black endogenous pigment

Which enzyme forms melanin?

Tyrosinase

What amino acid forms melanin?

Tyrosine

Which cells produce melanin?

Melanocytes

What is the only endogenous brown-black pigment?

Melanin

What is ochronosis?

Pigment deposition in connective tissue

What is hemosiderin?

Iron storage pigment

Color of hemosiderin?

Golden yellow-brown

What protein stores iron with hemosiderin?

Apoferritin

Which stain identifies hemosiderin?

Prussian blue stain

What disease causes systemic iron overload?

Hemochromatosis

Most common exogenous pigment?

Carbon

What is anthracosis?

Coal dust accumulation in lungs

Which cells ingest carbon pigment?

Alveolar macrophages

Where is inhaled carbon transported?

Lymph nodes

What color do anthracotic lymph nodes become?

Black

What is pathological calcification?

Abnormal calcium deposition in tissue

Two types of pathological calcification?

Dystrophic and metastatic

Gross appearance of calcification?

White gritty deposits

What is dystrophic calcification?

Calcium deposition in dead tissue

Serum calcium level in dystrophic calcification?

Normal

Where is dystrophic calcification commonly seen?

Atheromas and damaged valves

What complication can dystrophic calcification cause?

Aortic stenosis

First step of dystrophic calcification?

Initiation

Second step of dystrophic calcification?

Propagation

Where does calcification initiate intracellularly?

Mitochondria

What combines with calcium during propagation?

Phosphate

What is metastatic calcification?

Calcium deposition in normal tissue

Serum calcium level in metastatic calcification?

Elevated

Main cause of metastatic calcification?

Hypercalcemia

Cause of metastatic calcification from PTH excess?

Parathyroid tumors

Bone diseases causing metastatic calcification?

Paget disease and tumors

Vitamin D disorders causing metastatic calcification?

Vitamin D intoxication and sarcoidosis

How does renal failure cause metastatic calcification?

Secondary hyperparathyroidism

Microscopic appearance of metastatic calcification?

Eosinophilic deposits on H&E

What is cellular aging?

Progressive cellular deterioration

What accumulates during aging?

DNA damage and mutations

What is replicative senescence?

Reduced cell division from telomere shortening

What are telomeres?

Chromosomal end regions

What worsens cellular aging?

Chronic inflammation and stress

What slows cellular aging?

Calorie restriction and exercise

What happens to proteins during aging?

Misfolded proteins accumulate

What is defective protein homeostasis?

Loss of normal protein balance