Cell Injury and Cell Death

Cell Injury and Cell Death

Learning Objectives:

• Describe the ways cells adapt to stress and injury

• Understand how cell injury occurs following hypoxia and ischemia

• Summarise how oxidative stress causes cell injury

• Differentiate between cell death via necrosis and apoptosis

• Discuss the different classification of necrosis

• Recognise pathological calcification

Pathology - the study of disease

Pathophysiology - the study of abnormal changes in the body

Pathogenesis - the sequence of events and changes in the tissue that lead to disease

Aetiology - the cause of disease

Congenital disease - present before birth

Acquired disease - acquired after birth

Acute disease - sudden appearance of symptoms and signs that lasts a short time

Idiopathic - the cause of the disease is unknown

clinical manifestations - signs and symptoms of a disease

sequelae - a condition that is the consequence of a previous disease, treatment, or injury

Cellular Adaptation

• cells adapt to environmental stressors in order to protect themselves from injury

• can be result of exposure to chemicals, toxins, hormones, or physical stressors

• can be physiological or pathogenic

• typically reversible

• stressor continuous, adaptive capacity of cell exceeded, cell injury can develop leading to irreversible injury and cell death

1. Hypertrophy

2. Hyperplasia

3. Atrophy

4. Metaplasia

5. Dysplasia

Hypertrophy

Increase in cell size which results in increased size of organ

No new cells, existing cells larger

Seen in cells that have a limited capacity to divide

→ cardiac, skeletal muscle, uterus

Physiological hypertrophy

• when muscle size increases with exercise or extreme muscle building

• seen in uterus in pregnancy, which increases in size to accommodate growing foetus

• both examples will go back to normal size without stressors of pregnancy or extreme exercise

Pathological hypertrophy

• growth of cells caused by disease state

• e.g. heart, left ventriclar hypertrophy, typically result of long term hypertension

• heart compensate for increased BP and workload by getting bigger to produce higher contractile force

Hyperplasia

• An increased number of cells produced by an organ

• Generally occurs only in cells capable of replication, or organs with abundant stem cells

  

Physiological Hyperplasia

• hormonal hyperplasia is seen in the proliferation of glandular tissue in the breast in puberty and pregnancy

• compensatory hyperplasia where tissue regenerates after its removal or loss e.g. liver regeneration after resection, can manage with removal of 2/3 of liver, return to normal size due to hyperplastic reaction

Pathological hyperplasia

• often caused by excessive hormonal disruption or growth factor stimulation

• can increase risk of endometrial cancer

• e.g. endometrial hyperplasia that results in abnormal menstrual bleeding and benign prostatic hyperplasia

  

Atrophy

• shrinkage of size of cells

• entire tissue or organ reducing in size

• common in skeletal muscles, heart, sex organs, and the brain

causes

• decreased work load

• loss of nerve innervation

• loss of blood supply

• inadequate nutrition

• decreased hormonal stimulation

• aging

B12 deficiency

Metaplasia

• one cell type is replaced by another cell type

• a constant stressor can convert one cell type to another cell type that can deal with the stress better

• respiratory epithelium of a cigarette smoker will convert from ciliated columnar epithelium to stratified squamous epithelium to survive the damage of the cigarette smoke better

• ciliated columnar specialised for respiratory tract, captures any foreign particle inhaled and helps propel mucous out of lung

• smoker’s cough without this, preneoplastic/precancerous chnage to bronchioepithelium, can result in full neoplastic changes

Dysplasia

• disorderly proliferation of cells

• proliferation: the process where cells increase in number through growth and division

• loss of uniformity of cells and their architecture

• presence of dysplasia increases risk of the tissue for developing an invasive cancer

• example: traditional cervical screening tested for abnormal cells on the surface of the cervix

• cervical cancer

Cellular Injury

• hypoxia

• ischemia

• oxidative stress

• pathological calcification

• cells can only survive in narrow range of physiological parameters → Homeostasis

• Injury:

  

General causes of cellular injury

• physical: cold, heat, radiation, blunt force trauma

• chemical agents: toxins, cigarette smoke, heavy metals, carbon monoxide

• infectious agents: viruses, bacteria, parasites

• genetic conditons: sickle cell anemia

• nutritional deficiencies: lack of vitamins, minerals, glucose

• immune conditions: autoimmune disease

• hypoxic injury: lack of sufficient oxygen

Hypoxia

• when oxygen saturation of tissue falls below 90%

• significant hypoxia is below 88%

• whole body

causes

• inadequate oxygenation of blood

• decreased oxygen carrying capacity of the blood

or

• severe blood loss

consequences

• cyanosis, mental confusion, rapid breathing and if untreated can result in coma, seizures, and brain death

• seen in mountain climbers

• can measure oxygen saturation from arterial blood samples by looking at arterial blood gases → through pulse oxyometer, clips onto finger

• it measures change in light aborption in oxygenated and deoxygenated blood

• can give reasonably accurate reading of accurate oxygenation

Ischemia

• interruption of blood flow to cells and tissues

• this can include anything that blocks blood supply

• e.g. a blood clot, atheroscelosis, or a traumatic injury to a blood vessel (frostbite)

• blockage of the blood vessel also blocks the movement of all fluids such as removal of waste

• this can lead to necrosis (death of tissue) and build up of metabolic waste products

• frostbite: extreme cold caused vasoconstriction of blood vessels in attempt to conserve body heat

• ischemia can cause hypoxia, but hypoxia doesn’t lead to ischemia

Oxidative stress

• an imbalance between free radicals and antioxidants in the body

• free radicals: oxygen containing species with a single unpaired electron in an outer orbit

• → unstable

• → react readily with DNA, proteins, or lipids (organic molecules) and steal their electrons to become stabilised

• →this destabilises the cell and a chain reaction is started with electrons being stolen from other molecules

• called Oxidative stress - can cause pathological conditions in the body: some neurodegenerative diseases, gene mutations, cancers etc.

• some factors can increase production of free radicals: pollution, smoking, alcohol consumption

• donate free electron, can reduce activity of free radical

Pathological calcification

Dysrtrophic calcification:

occurs in areas of degenerated and dying tissue despite normal levels of calcium and normal calcium metabolism

• commonly seen in advanced atherosclerotic arteries

• reduces the flexibility of the arteries

• also seen in damaged heart valves

Metastatic Calcification

• calcification that occurs with hypercalcaemia

• causes: conditions that cause bone resorption

• → hyperthyroidism, bone marrow tumours, vitamin D disorders etc.

• → affects gastric mucosa, kidneys (failure included in picture), lungs, systemic arteries, pulmonary veins

  

Cell Death

Causes:

• Apoptosis

• Different types of necrosis

Apoptosis

• programmed for organised cell death

• essential for human development

• provides a protective mechanism against disease

• apoptosis can also occur after exposure to radiation and cytotoxic drugs

STAGES OF APOPTOSIS

• cell membrane remains intact

• enzymes break down cell contents

• cell condenses and undergoes fragmentation

• cell forms smaller apoptotic bodies that are consumed by phagocytes

Necrosis

• is the major pathway of cell death due to irreversible injury

• can be caused by physical injuries: burns, lacerations, hypothermia, oxygen deprivation

• ischemia can cause this

• pathological processes and results in a premature death of tissue due to autolysis

• in autolysis: the cell membrane is broken down and cellular contents released, including cellular enzymes

  

Coagulative and liquefactive necrosis

coagulative necrosis

• architecture of the tissue is preserved

• tissue has a firm texture

• infiltration of leukocytes

• common in heart and kidney

• myocardial and renal infarction

• kidney: dead cells → viscous liquid, yellow

liquefactive necrosis

• dead cells are digested and transformed to a viscous liquid

• tissue architecture lost

• necrotic material is commonly yellow discoloured due to the presence of neutrophils

Caseous necrosis

• commonly seen in tuberculosis

• dead tissue appears yellow/white and cheeselike

• dead cells and debris are enclosed in a distinctive inflammatory border

• in the case of TB, this is known as a granuloma

Gangrenous necrosis

• fingers completely black

• result of dead tissue from no blood getting to area

• tissue not salvagable

• dry gangrene: type that does not have a bacterial infection

• wet gangrene: includes bacterial infection and tisk of sepsis is high

Necrosis vs Apoptosis