Week 3: Cell injury and healing

What are the two types of cell death?

Apoptosis and necrosis.

What type of cell adaptation is atrophy?

A decrease in tissue mass due to decrease in size or number of cells after normal growth

What type of cell adaptation is Hyperplasia?

An increase in tissue mass due to increase in number of cells.

What type of cell adaptation is Hypertrophy?

An increase in tissue mass due to an increase in the size of existing cells.

What type of cell adaptation is Metaplasia?

A change in cell type where one differentiated cell type is replaced by another.

What cell types are an example of Metaplasia?

Pseudostratified columnar to Striated Squamous

What are the three characteristics of Necrosis?

Membrane rupture

Protein Denaturation

Inflammation

What are the three characteristics of apoptosis?

Programmed cell shrinkage

Fragmentation

No inflammation

What are the two phases of apoptosis?

Initiation phase

Activation phase

What are the two pathways of the initiation phase?

Intrinsic pathway (mitochondrial)

Extrinsic pathway (death receptor-initiated)

What is the main characteristic of the activation phase?

caspase enzyme cascade (8,9,10,3)

Why is enzyme three important in the activation phase?

Authorizes denaturing of DNA

Which cellular change involves cell shrinkage and fragmentation?

Apoptosis

What are the three types of necrosis-nuclear changes?

Pyknosis

Karyorrhexis

Karyolysis

Which necrosis nuclear change condeses the nucleus?

Pyknosis

Which necrosis nuclear change causes a fragmented the nucleus?

Karyorrhexis

Which necrosis nuclear change causes a dissolution of the nucleus?

Karyolysis

What are the three characteristics of the morphology of apoptosis?

Condensation of chromatin

Condensation of cytoplasm

Fragmentation of the cell in to small-bound segments

What is the fragmentation of the cell into small membrane bound segments?

apoptotic bodies

Shrunken cell and fragmentation into small membrane bound bodies?

Apoptosis

Swollen cell and rupture of plasma membrane

Necrosis

What type of cell death is Pyknosis and karyolysis

Necrosis

Chromatin condensation and fragmentation of the nucleus

necrosis

Which type of cell death has inflammation abscent?

Apoptsis

Which cell death has inflammation present?

Necrosis

Which cell death has dead contiguous cells?

Necrosis

What are the 5 different types of necrosis?

Coagulative

Caseous

Liquefactive

Gangrenous

Fat

What are the common causes of Coagulative Necrosis?

Loss of blood supply (ischemia)

Free Radicals

Toxins

Burns

X-rays

What are the characteristics of the appearance of Coagulative Necrosis?

Gray or white- unless mixed with blood

Depressed compared to surrounding living tissue

What is the characteristics of the hisologic appearance of Coagulative Necrosis?

Outline of the necrotic cell is preserved

Homogeneous strongly acidophilic or eosinophilic cytoplasm

Nuclear changes (Pyknosis, Karyolysis, Karryorrhexis)

A 3-day-old foal is found dead unexpectedly. Postmortem examination reveals an umbilical abscess, septic joints, and hemorrhages throughout the body. Multifocal renal infarction are present bilateraly. What microscopic features would you expect to see within the areas of the renal infarction?

A. Normal cellular architecture on renal tubules?

B. Enhanced cytoplasmic detail of tubular epithelial cells

C. Renal epithelial cells with hypereosinophilic cytoplasm and loss of cell borders

D. Normal nuclei with open chromatin patterns

C. Renal epithelial cells with hypereosinophilic cytoplasm and loss of cell borders

What type of cell death is White Muscle Disease?

Coagulative Necrosis

What causes White Muscle Disease?

Acute oxidative injury (free radical)

What is another name of White Muscle Disease?

Nutritional Myopathy

What nutrients are you deficient in to get White muscle disease?

Vitamin E

Selenium

What does white muscle disease demonstrate?

Importance of antioxidative mechanisms

What are the characteristics of the histology of White Muscle Disease?

Multifocal to coalescing coagulative necrosis

Increase in eosinophilia and preservation of myofiber architecture

What are the three characteristics of oxidative stress?

Damage caused by free radicals

A free radical is any molecule with unpaired electron

Includes reactive oxygen species

What are the three types of ROS?

Super anion

Hydrogen Peroxide

Hydroxyl Radical

What are the 5 sources of free radicals?

Endogenous

Metabolic enzymatic reactions

metal cations (Cu+ Fe+)

Inflammatory disease

Neoplastic disease

What are examples of exogenous?

Chemicals

drugs

toxins

radiation

tissue trauma

What does superoxide dismutase do?

Catalyzes the superoxide radical into oxygen or hydrogen peroxide

What does catalase do?

Catalyses the conversion of hydrogen peroxide or water and oxygen

What doe glutathione peroxidase do?

Catalyzes the conversion of lipid hydroperoxides to their corresponding alcohols and reduces free hydrogen peroxide to water

Oxidative Stress causes a type of cell injury that is an important component of many chronic diseases. In addition, there is an acute, oftern fatal, disease in veterinary medicine that is also caused predominately by free radical injury.

A) Acute cell swelling

B)White Muscle Tissue

C)Granulomatous hepatitis

D) Acute Renal Infarction

B) White muscle disease

What is the cause and the pathogenesis of White Muscle Disease?

Cause: Deficiency of Vitamin E and Selenium

Pathogenesis: Free Radical

What is the common cause of Caseous Necrosis?

Toxins of certain micro-organisms

What does the gross appearance of caseous necrosis look like?

Milk curd or cheese

Dry, greasy, and breaks easily

What does the Histological appearance of Caseous Necrosis look like?

Loss of cell outline and normal tissue architecture

Granular and stain purple

What is the common causes of liquefactive necrosis?

Loss of blood supply (Ishemia)

Free Radicals

Toxins

Burns

X-rays

What does the gross appearance of Liquefactive necrosis look like?

Occurs in the CNS and abscesses

Small or large cavities containing yellowish fluid

Necrotic tissue is converted to liquid phase

What does the Histologics appearance of Liquefactive Necrosis look like?

Clear spaces with or without pink staining proteinaceous precipitate in the necrotic area

Why does the tissues of the brain and spinal cord liquifies after death?

The high lipid content and poor connective tissue content

What attributes to the liquefaction of abscesses?

Toxins present in some bacteria

Abscess leukocytes produce hydrolytic enzymes that liquify dead tissue in inflammatory areas

What are the 4 different types of Fat Necrosis?

Enzymatic

Traumatic

Nutritional

Idiopathic

What does the gross appearance of Fat Necrosis look like?

White opaque firm and grandular

What does the Histological appearance of Fat Necrosis look like?

Large shadowy outline with blueish or purple material in areas of necrosis

Necrotic adipose tissue with saponification

Where does Gangrenous necrosis usually occur?

Occur in distal aspects of extremities and dependent parts of organs

What are the two types of Gangrenous Necrosis?

Wet and Dry

What is the common cause of Dry Gangrene?

Loss of blood supply resulting in coagulative necrosis

What is the common cause of wet gangrene?

Infection of necrotic tissue by certain bacteria

What are the characteristics of dry gangrene?

Coagulation necrosis of an extremity followed by mummification

No bacterial involvement

Gross appearance

Dry Leathery textureW

What are the characteristics of wet gangrene?

Combination of coagulation necrosis and liquefactive necrosis

Occurs with infection

Red-Black and wet tissue

What is an example of a bacteria that can cause wet gangrene?

Staphylococcus

What type of necrosis has a cheese like appearance?

Caseous

What type of necrosis preserved cell outline and tissue architecture?

Coagulated

What type of necrosis is firm white fat?

Fat

What type of necrosis has hard necrotic tissue in the distal extremity

Dry gangrene

What type of necrosis has cavitated CNS tissue?

Liquefactive

What type of necrosis has soft wet necrotic tissue in the distal extremities?

Wet gangrene

What type of necrosis has grey depressed tissue?

Coagulative

What are the characteristics of Healing by regeneration?

Dead cells are replaced by an identical cell type

Best chance of tissue homeostasis being restored

What are the characteristics of healing by repair?

Dead cells must be replaced by another cell type; usually fibrous scar tissue

Homeostasis is restored or nearly restored

What type of healing requires that the progenitor cells and underlying supportive tissue is still in place?

Healing by Regeneration

What type of healing occurs if there is loss of the progenitor cells and underlying supportive tissue?

Healing by repair

What are the three type of regenerative cells in the body?

Labile

Stable

Permanent

What are the characteristics of a labile cell?

High regenerative capacity

Tissue are regenerating for the lifespan of the host

Never in G0

Very Short G1

Where would you find Labile cells?

Skin

GI tract

Genitals

Bone marrow

A 4 month old Labrador retriever was just adopted from a breeder. No history of deworing or vaccination. The patient is lethargic and has bloody diarrhea. On physical exam, the abdomen is tense and painful, and the animal has a high temperature.

What body system is involved?

The Gastrointestinal Tract

What are some causes of Diarrhea and a tense abdomen?

Toxins

Foreign Bodies

Viruses

Bacteria

What do you run first to narrow does the possibilities of the Diaherra?

X-rays

Snap test

Parvo test

Fecal cytology

Fecal FloatWha

Diagnostic Tests of the Lab were run these were the results:

Xrays: no significant finding

Fecal Float: negative for parasites

Fecal cytology: Mixed bacteria consistent with normal flora

Parvovirus antigen test: Positive

What does the dog have?

Parvo

What are the characteristics of Canine Parvovirus-2

Highly virulent virus of young dogs

Infects rapidly dividing labile cells which are the crypt cells in the GI

What body system is effected by Parvo and what happens?

GI tract

Infects Labile cells resulting in epithelial necrosis of the mucosa and inability to repopulate lost cells

What is leukopenia?

Low white blood cell count

What causes severe leukopenia?

Consumption of immune cells

Necrosis of labile cells

How does Parvo effect WBCs?

By causing necrosis of WBC in bone marrow which means no production of inflammatory cells to fight off infection.

How long do clinical signs of parvo last and why?

7-10 days

For parvo to run its course and the labile cells are able to repopulate ( heal by regeneration)

Which cells regenerate when stimulated

Stable Cells

What cells make up organs like liver, kidneys, pancreas, adrenal gland, bone, tendon, nerve and smooth muscle

Stable

What kind of regenerative capacity does the liver have?

Highly rengenerative

What type of regenerative capacity does the kidney have?

Can only regenerate some cell types specifically in the tubules

What do stable cells respond to?

Growth mediators.

Hormones

Other factors

What fungi produces Aflatoxin?

Aspergillus spp.

Where is Aspergillus usually found and what does this cause?

In contaminated feed, acute ingestion results in poor growth and liver necrosis

What type of necrosis occurs in the liver during Alfatoxin?

Hepatic Coagulative

When you test the pigs' blood with Alfatoxin, you find a mild elevation of liver enzymes, indicating liver necrosis. What will you tell the farmer about the pig’s long-term prognosis for recovering hepatic function?

Mild necrosis: Progenitor cells and underlying connective tissue are spared,

Hepatocytes are stable cells and can regenerate

When you test the pigs' blood with Alfatoxin, you find a severe elevation of liver enzymes, indicating liver necrosis. What will you tell the farmer about the pig’s long-term prognosis for recovering hepatic function?

Severe necrosis: loss of underlying connective tissue and progenitor cells

May not be enough cells to repopulate the tissue

If that animal survies but there is a loss of progenitor cells and supporting structures these tissues will undergo what type of healing?

Repair

Bone is made up of what type of regenerative cells?

Stable