Path1: Cell injury

Reversible cell injury

Cellular swelling

Irreversible cell injury

Cell death

1. Reversible injury, cell recovery, and return to normal function

2. Apoptosis and programmed cell removal

3. Cell death and necrosis

What are the 3 outcomes of cell injury?

Apoptosis

Death of cells that occurs as a normal and controlled part of an organism's growth or development

1. Within range of Homeostasis

2. Cell membrane left relatively intact (pumps)

3. Mitochondria able to sustain energy demands

4. Mild and/or short-lived

5. Cell returns to its original state

What are the characteristics of reversible cell injury?

-change in oxygen level (brief hypoxia or anoxia)

-low concentration of toxins

What can cause reversible cell injury?

Hypoxia

decreased oxygen supply

Anoxia

Complete deprivation of oxygen

injury stops->cell goes back into the original steady state

If adverse conditions causes a cellular response that remains within the range of homeostasis:

1. Brief hypoxia, anoxia or low concentration of toxins decreased function in Na/K pump

2. Na/K pump can't maintain concentration gradient --> Na+ flows into cell (Cl-follows)---> increased NaCl inside cell

3. Water flows easily into cell ----> Swelling of cytoplasm and organelles

What's hydrophic changes in the cell?

-swollen microvilli

-Vacuolar degeneration: invagination of the cell membrane

-swollen mitochondria and dialated RER

-loss of intercellular contact (cellular junctions-desmosomes)

How do reversible cell injury affect cellular structure?

1. Reduced energy production (swollen mitochondria generate less ATP)

2. Decreased protein synthesis (pH of cell becomes acidic which slows metabolism)

3. Increased autophagy (cell pH is acidic-->lysosomes enzymes are released)

What are some functional changes of reversible cell injury?

cause is removed or energy source is restored (oxygen)

Hydrophic change is reversible if:

mild; short lived

Reversible cell injury is typically ____________ or ______________ so cell can revert back to the steady state homeostasis

1. Anoxia and prolonged hypoxia

2. Heavy doses of toxins

3. Other overwhelming insults (severe trauma)

4. Microbes (pathogens)

5. Inflammation and immune reactions

6. Genetic/ metabolic disorders

What can cause irreversible cell injury?

nucleus

In irreversible cell injury, ___________________ is damaged

1. Pyknosis ("dense")-condensation of chromatin (formed by complex of DNA)

2. Karyorrhexis-nucleus break down into small particles (nuclear dust)

3.Karyolysis-Lysis of chromatin (as a result of enzymatic digestion)

What are the stages of nuclear damage in irreversible cell injury?

permeability

Irreversible cell injury also cause changes in the cell membrane _______________

cell integrity; cell membrane

Nuclear changes cause Loss of ______________ and rupture of the ________________

Cytoplasmatic enzymes

Dead cell release ___________________________ into extracellular fluid and into blood

AST: Asparate Amino Transferase

ALT: Alanine Transferase

LDH: Lactate Dehidrogenase

What are some cytoplasmatic enzymes?

cellular injury

Cytoplasmatic enzymes shown in laboratory blood tests are sign of ________________

Myocardial infarct or viral hHepatitis

Cytoplasmatic enzymes elevated in:

energy production (ATP)

Low oxygen will cause low ____________________

1. Obstruction of airway (suffocation secondary to drawing)

2. Decreased oxygen transportation (pneumonia, severe anemia)

3. Inability of cell to use oxygen (cyanide poisoning inhibits cellular oxidative enzymes)

What cause low oxygen level in the blood?

Re-oxygenation

Short lived reversible cell injury due to Hypoxia may be repaired by ________________

-Oversupply of oxygen ----> oxygen toxicity

-too much oxygen too fast may form Oxygen radicals (Hydrogen peroxide & Superoxide)

What are the risk of Re-oxygenation?

-direct toxin

-indirect toxin

-drug and alcohol

What are some toxins?

Direct toxin

Mercury-deactivation of very important cellular enzymes

Indirect toxin

When ingested is metabolized into a toxic free radical

eg. Carbon tetrachloride (commercial metal cleaning product)

1. Bacteria produce toxins---> may inhibit various cell functions

2. Viruses invade cells and kill from within

How do microbial pathogens cause cell injury?

Food poisoning: exotoxins released by bacteria cause GI tract cells poisoning

-nausea, vomiting, diarrhea

What is an example of bacteria causing cell injury?

some viruses integrate into cellular genome ---> the genetic material of these viruses encodes the production of foreign protein---> causes the immune system to attack it's own cell

How do virus invade the cell?

Biologically active substances: cytokines, interferons, complement proteins

-produced by the body in response to infection or in immune reactions

What are the mediators of inflammation and immune reactions?

They eliminate infectious diseases but also kill own body's cells

How do mediators of inflammation and immune reactions cause cell injury?

Many genetic diseases cause disturbances to metabolism and accumulation of toxic metabolites

How do genetic and metabolic disturbances cause cell injury?

Diabetes Mellitus (carbohydrate metabolic disease)

High blood sugar causes pathological changes to small blood vesslels---> diabetic microangiopathy--->ischema: inadequate blood supply to a local area due to blockage of blood vessels leading to that area

What is an example of metabolic disturbance causing cell injury?

prolonged exposure to adverse or exaggerated normal stimuli

Cell adaptations occur after:

1. Atrophy

2. Hypertrophy and Hyperplasia

3. Metaplasia

4. Intracellular accumulations

5. Aging

What are the main forms of adaptation?

Atrophy

decrease in size of a cell, tissue, organ, or the entire body

1. physiologic & predictable

2. pathological

What are two types of atrophy?

-Atrophy of thymus after puberty

-Aging: brain atrophy because nerve cells cannot regenerate

- atrophic bones: elderly people more prone to fracture

What are examples of physiological atrophy?

-lack of nutrition

-chronic ischemia

-denervation (muscle)

-inactivity (muscle)

Pathologic atrophy is caused by:

Hypertrophy

increase in size of tissue or organs due to enlargement of individual cells

-hypertrophy of the heart in hypertension

-hypertrophy of skeletal muscles in body builder

What are examples of pure hypertrophy?

Hyperplasia

increased number of cells in a tissue or organ

-often combined with hypertrophy

hormonal stimulation

Pure hyperplasia typically occurs as a result of ___________________

1. Endometrial hyperplasia caused by the action of estrogen

2. Benign Prostatic hyperplasia in elderly men

3. Callus (corn) on the heels (tight shoes)

4. Hyperplastic polyps of intestine

5. Nodular hyperplasia in liver

What are some examples of hyperplasia?

Metaplasia

change of one cell type into another

smokers - Columnar cells of the bronchial mucosa---> stratifies squamous epithelium

What is an example of metaplasia?

reversible

Metaplasia is _________________ change

Dysplasia

-disorderly arrangement of cells and nuclear change

If stimulus remains, the metaplasia may progress to ____________________

Neoplasia (malignancy)

Dysplastic cell can progress to ________________

finite

All the cells in human body have ___________ life span

stem cells

some cells may be replaced from _________________

brian cell

Some cells are irreplaceable, such as _____________

1. Necrosis

2. Apoptosis

Cell death occurs in two forms:

Necrosis

Localized death of cells or tissues in a living organism

Apoptosis

Programmed death of single cells or tissues within a living organism

Autolysis

Death of cell and tissues in a dead organism

exogenuously (from the environment)

Necrosis is _________________ induced cell death

1. Coagulative necrosis

2. Liquefactive necrosis- in the brain

3. Caseous necrosis -Tuberculosis

4. Enzymatic fat necrosis -acute pancreatitis

What are forms of necrosis?

Coagulative necrosis

What is the most common type of necrosis?

Anoxia

What is the cause of Coagulative necrosis?

cell membrane is preserved, organelles and nucleus coagulate

What is the characteristic of Coagulative Necrosis?

solid internal organs: heart, liver, kidneys

Which organs are affected by Coagulative Necrosis?

pyogenic bacteria (pus)

Tissue is completely digested by hydrolytic enzymes

What is the cause of Liquefactive Necrosis?

Dissolution of tissues --> soft and liquefy

What is the outcome of Liquefactive Necrosis?

Brain, skin, joints

Which organs are affected by Liquefactive Necrosis?

TB patients ---> center part of Tuberculous Granuloma becomes necrotic and cells fall apart

What is the cause of Caseous Necrosis?

yellow-white and cheesy

How does tissue in Caseous necrosis appears?

lungs

Which organ is affected by Caseous Necrosis?

Granulomas

collections of inflammatory cells at site of tissue infection

Enzymatic fat necrosis

Form of liquefactive necrosis caused by the action of lipolytic enzymes

-Limited to fat tissue

Rupture of Pancreas

-cause enzymes release into adjacent fat tissue, degrade fat into glycerol and free fatty acids

-free fatty acids bind with calcium ---> forms calcium soaps

What is the cause of Enzymatic fat necrosis?

1. Gangrene

-often seen in necrotic tissue especially on toes and lower extremities (diabetic atherosclerosis)

2. Calcification

What are the complication of necrosis?

Bacterial infection of Coagulated tissue ---> inflammation and secondary liquefaction-> wet gangrene

Necrotic tissue dried out--> dark black and mummified ->Dry gangrene

What cause Gangrene?

Dystrophic calcification

Necrotic tissue attracts calcium salts

-arteries with atherosclerosis, damaged heart valves, tumours

Metastatic calcification

Hypercalcemia followed by deposition of calcium salts in Normal tissues

Hyperparathyroidism

What is the most common cause of Hypercalcemia?

single cells

Apoptosis affects:

Exogenous: Long-lasting viral infection

Endogenous: Lack of growth factors in brain cell

What are the cause of Apoptosis?

energy

Apoptosis requires ____________

Physiological apoptosis

plays an important role in formation of many body parts

1. Muscular dystrophy (genetic disease)

2. Transplanted organs

3. Chronic lymphocytic leukemia

What are some examples of pathologic apoptosis?

Muscular dystrophy

Deficiency of specific cell components cause lack of cell proteins --> the skeletal muscle undergo apoptosis

Transplanted organs

Transplanted cells are attacked by the host's immune cells

Chronic lymphocytic leukemia

Mutation of the proaptotic gene (suicidal gene) ---> the lymphocytes do not die at their normal rate ----> high number in blood ---> Leukemia

Necrosis

1. Exogenous injury

2. Vital processes are inhibited

3. Multiple cells, organs

4. Cell membrane rupture, tissue death, bacterial infections

Apoptosis

1. Exogenous or endogenous

2. Actie programmed process

3. single cells

4. Phagocytosis by macrophage