Apoptosis/Necrosis Flashcards by Ashley Bryant

A diagnosis based on case history, c/s, physical exam

Clinical diagnosis

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List of diseases that could account for clinical findings/lesions

Differentials

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Diagnosis based on changes in biochemistry, hematology, cytology

Clinical pathological

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Diagnosis based on clonclusive evidence that confirms cause of disease. What may it require?

Eitiologic May require ancillary testing

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Diagnosis based on predominant lesion or lesion pattern

Morphologic diagnosis

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Diagnosis based on conclusive evidence from clinical data and observed lesions

Definitive

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Causes of cell membrane injury

1) Transmembrane proteins (hijacked by microbes to enter cell)
2) Oxidative stress from free radicals
3) Loss of phospholipids through decreased synthesis/increased degradation
4) Cytoskeletal abnormalities

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Consequences of cell membrane injury

1) Loss of Na pump –> cell swelling
2) Increased permeability –> Ca includx - Mitochondrial damage - Apoptosis
3) Injury to RER and ribosome dissociation —> inhibited protein synthesis

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Oxidative damage is caused by (3)

1) Superoxide anion
2) Hydrogen peroxide
3) Hydroxyl radical

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Endogenous source of oxidative damage

1) Enzymatic reactions: lipoxygenase, prostaglandin synthetase, lipid peroxidation…etc
2) Transition metal cations (Cu, Fe)
3) Inflammation and tissue injury –> increased free radical production

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Exogenous sources of oxidative damage

Chemicals

Drugs

Toxins

Radiation

Tissue trauma

Aging

Stress

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Antioxidant defense mechanisms (5)

1) Superoxide dismutase (SOD)–> catalyzes superoxide anion to hydrogen and oxygen
2) Catalase: catalyzes hydrogen peroxide to water and oxygen
3) Glutathione perioxidase (catalyzes llipid hydroperoxidases to water and oxygen)
4) Vitamin E: neutralizes effects of free radicals
5) Selenium: co-factor of glutathione peroxidase

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What is White Muscle Disease caused by

Deficiency of Vit E and Selenium Muscle is oxidized, turns necrotic

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Implications of oxidative stress on health

1) Inflammatory conditions result in chronic oxidative stress causing ORGAN FAILURE and ACCELERATED AGING
2) Chronic oxidative stress can also cause CARCINOGENESIS and NEOPLASTIC DISEASE

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Causes of damage to mitochondria (2)

1) Oxidative stres
2) Calcium influx

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Consequences of damage to mitochondria (2)

1) Reduced ATP production
2) Leakage of proapoptopic proteins Cell death/apoptosis

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Causes of damage to nucleus

1) Oxidative stress: damages nuclear envelope DNA damage:
2) Reactive O2 species, reactive carbonyl species, lipid peroxidation products, alkylating agents, hydrolysis
3) Chemicals, drugs, radiation
4) Random mutations
5) DNA repair malfunction

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Cells most susceptible to hypoxia

Neurons

Hepatocytes

Cardiac myocytes

Renal tubules

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Pathogenesis of hypoxia

Lack of oxygen —> reduced ATP —> loss of Na/K pump function—> influx of ions (Na, Ca) and water –> cell swelling

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What is first step of reversible cell injury

Hydropic degeneration

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Types of cell injury

Reversible

Irreversible

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Gross features of cell swelling

Organ enlargement, pallor

Increased fluid in tissues (noticeable during cutting)

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Histological features of cell swelling

1) Cell enlargement
2) Cytoplasmic vacuolation
3) Cell membrane blebbing

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What is ballooning degeneration? What is it associated with?

Swelling that occurs in EPIDERMIS Cytoplasm becomes clear.

Peripheral nuclei Inclusion bodies (viral)

Usually associated with viral infection

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What is cytotoxic edema? Why is this area so susceptible

Swelling that occurs in CNS Susceptible to hypoxic injury due to lack of anerobic glycolysis

What are three types of irreverisible cell damage

Necrosis Apoptosis Post-mortem autolysis

Nuclear condensation, nucleus appears shrunken and dark

Pyknosis

Nuclear destruction

Karyolysis

Nuclear fragmentation

Karyorexis

Nuclear and cytoplasmic changes of necrosis

Pyknosis Karyorrhexis Kryolysis Cytoplasmic: 1) Eosinophilia (proteins) 2) Loss of boundaries, cell rupture 3) Loss of cell adhesions, individualization

Which type of necrosis occurs with sudden loss of blood - resulting in severe acute hypoxic injury

Coagulation necrosis

Is coagulation necrosis acute or chronic

Acute

Which type of necrosis has retention of cell outlines

Coagulation

Which type of necrosis has cytoplasmic hypereosinophilia and pyknotic or absent nuclei

Coagulation

Which type of necrosis occurs with bacterial infections

Caseation necrosis

Which type of necrosis manifests in granulomatous nodules?

Caseation necrosis

Appearance of caseation necrosis

Cottage cheese!

Which type of necrosis has an inflammatory zone

Caseation necrosis

What is histological appearance of caseation necrosis

Loss of tissue architecture Granulomatous/pyogranulomatous inflammation and cellular debris

Where do you find liquefactive necrosis

CNS, abscesses

Is caseation necrosis acute or chronic

Chronic

What is the chronic type of liquefactive necrosis

In CNS

Where does acute liquefactive necrosis occur

Abscess

What is malacia

Cavities filled with liquid Common in liquefactive necrosis in brain and spinal cord

Is malacia in CNS acute or chronic

ACUTE - severe cases result in death Mild cases will heal with glial scaring (chronic lesions)

Viscous, opaque, white/yellow/green fluid is known as what

Supparative inflammation

Is supparative necrosis associated with inflammation

Yes! Hyperemic ring

You see histologically an inflammed tissue with lots of degenerative neutrophils and bacteria. What type of necrosis?

Supparative (liquefactive)

Can supparative necrosis become chronic

Yes, if body walls it off

What is a combo of coagulative and liquefactive necrosis

Moist gangrene

Which type of necrosis is associated with bacteira

Moist and gas

What type of necrosis is coagulation and mummifcation

Dry necrosis

Which type of gangrene is acute? Which is chronic

Acute: dry Chronic: moist

What is a huge risk of moist gangrene

Fatal septicemia after tissue sloughing

You have a patient with black, shriveled tissue. What is this?

Dry gangrene

Your patient has malodorous, brown tissue that is soft. What is this

Moist gangrene

Your patient has black tissue with a hemorrahagic exudate that contains bubbles. What is this?

Gas gangrene

What type of bacteria are associated with gas gangrene

Anerobes such as Clostridium

Sequelae of necrosis

1) Inflammation - Neutrophils digest and liquify - Macrophages phagocytose 2) Healing/replacement - Regeneration - Fibrosis 3) Seuqestration - Occurs when necrotic tissue doesnt heal and is removed from body via degradation and phagocytosis (bones)

T/F cells undergo apoptosis first swell

False, they shrink

T/F inflammation is an important step in apoptosis

False! No inflammation in apoptosis, only in necrosis

Morphology of apoptosis (4)

1) Chromatin condensed 2) Cytoplasm condensed 3) Apoptotic bodies: fragmentation of cell in small membrane bound segments 4) Continue maintenace of cell membranes, to prevent inflammation

Physiological causes of apoptosis (2)

Fetal development Leukocyte apoptosis

Causes of pathologic apoptosis

1) Hypoxia 2) Withdrawal of growth factors 3) Cell mediated immune responses

Intrinsic pathway of apoptosis

Regulated by mitochondria 1) Initiated by withdrawal of growth factors/hormones or DNA damage 2) Release of pro-apoptotic factors from mitochondria. Caspase activation ---\> apoptosis

Extrinsic pathway of apoptosis

Initated by death receptors/ cytotoxic T-cells Fas/FADD signalling followed by caspase activation and apoptosis

Whats the name of the enzyme cascade in apoptosis

Capase enzyme cascade

What is autophagocytosis

Cellular house-keeping Removes and recycles damaged organelles and protein

Two types of pathological calcifications

Dystrophic - at site of injury and necrosis Metastatic - secondary to hypercalcemia

Examples of dystrophic calcificaiton (4)

1) Necrotic myocardium/skeletal muscle (white muscle disease) 2) Granulomas 3) Calcinosis cutis (collagen degeneration and calcification) due to hydroadrenocorticism ) 4) Calicnosis circumscripta : repetitive injury followed by calcification

6 causes of hypercalcemia in vet med \*\*

1) Renal failure 2) Primary hyperparathyrodism (rare) 3) Paraneoplastic (lymphoma and anal sac adenocarcinoma produced PTH-related protein) 4) Vit D toxicosis 5) Destructive bone tumor 6) Severe granulmatous disease

What causes irreversible cell damage

Oncotic necrosis

Calcinosis cutis is an example of what

Dystrophic calcification

What type of necrosis involved anerobic bacteria

Gas gangrene

What type of necrosis involved intracellular bacteria

Caseation necrosis

What type of necrosis involves extracellular bacteria

Suppurative inflammatory necrosis

Whats this