أسئلة الثانية باثو PPPM (قبل التعديل)

Cell Injury: Definitions

• Cell injury involves changes to the structure of the cell due to internal and external stressors.
• Injured cells can have altered homeostasis.

Homeostasis and Cell Injury

• Homeostasis: Cells maintaining stable physiological parameters
• Cellular dysfunction leads to organ dysfunction presenting as clinical expressions.

Causes of Cell Injury

• Hypoxia ( Low tissue oxygen) can be caused by:
  • Ischemia by arterial occlusion
  • Inadequate oxygenation from heart or lung disease
  • Decreased oxygen supply (anemia)
• Infectious Agents: Viruses, Bacteria and Fungi
• Physical Agents: Trauma, Heat, Cold and Radiation
• Chemical Agents: Concentrated acids, alkalis, poison and drugs
• Immunologic Reactions: Autoimmune diseases
• Nutritional Disturbance: Excess(obesity) or deficiencies in protein and vitamins
• Genetic and Chromosomal Defects

Cell Injury Effects

• Effects are determined by nature, duration and severity of the injurious agents.
• Effects are also determined by the type and state of the injured cell.
• Brain tissue is very sensitive to hypoxia (2-5 min).
• Skeletal muscles can adapt to hypoxia for (2-6 hours).

Forms of Cell Affection

• Cell affection can be from the following:
  • Adaptation
  • Reversible cell injury
  • Irreversible cell injury
  • Intracellular and extracellular deposits

Cell Injury Overview

• Normal cells under stress can either adapt or undergo reversible injury.
• Cell injury can be severe and progressive, leading to irreversible cell injury, which can result in necrosis or apoptosis.

Adaptation -Definition

• Adaptation is a modification of cell structure and functions in response to excess physiologic or pathologic stress to preserve the vitality of cells.
• It's a reversible process
• Injury occurs when stress exceeds the cell's adaptive capacity.

Types of Adaptation

• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
• Dysplasia

Atrophy - Definition

• Atrophy: decrease in size of organ by a decrease in the size and/or number of its cells.
• Cells become smaller because:
  • Decreased protein synthesis
  • Increased protein degradation
  • Cell deaths.
• This can be due to decreased workload, blood supply, nutrition, hormones, or denervation.

Causes of Atrophy

• Physiological causes include: Aging, Uterus atrophy post labor and Thymus atrophy after puberty
• Pathological causes include: Disuse atrophy bone fracture, Neurogenic atrophy (denervation), Thermal atrophy(undescended testis), and issues with Ischemia, nutrition or the endocrine system

Hypertrophy - Definition

• Hypertrophy: increase in size of organ due increase in size of its constituent cells.
• This is due to an increased synthesis of structural proteins and organelles.
• Causes include increased functional demand, growth factors, and hormones.

Causes of Hypertrophy

• Physiological causes include uterine hypertrophy and muscle hypertrophy in athletes.
• Pathological causes include left ventricular hypertrophy in systemic hypertension

Hyperplasia - Definition

• Hyperplasia: Enlargement of organ due to increase in the number of its component cells.
• This is due to Cell proliferation.
• The cases include increased functional demand, growth factor stimulation, and hormonal stimulation.

Causes of Hyperplasia

• Physiological causes include hyperplasia of the female breast during puberty, pregnancy, and lactation.
• Pathological causes include bone marrow (after hemorrhage), skin or mucous membrane (around ulcer), liver cells (after partial destruction), and prostate & endometrium, stimulated by hormones.

Metaplasia - Definition

• Metaplasia is a change of one type of tissue to another type of the same category.
• It involves the reprogramming of stem cells.
• Stem cells differentiate along a new pathway that is better able to tolerate physical or chemical stress.

Characteristics of Metaplasia

• Always pathological.
• Respects histogenic boundaries, and is reversible.
• There is a risk of malignancy

Examples of Metaplasia

• Squamous metaplasia of respiratory epithelium in smokers.
• Intestinal metaplasia of the esophagus in reflux esophagitis (Barrett's esophagus).
• Squamous metaplasia of the urinary bladder in bilharziasis.

Reversible Cell Injury - Definition

• Degeneration (Sublethal) is caused by a mild injurious agent for a short duration.
• It Affects active functioning cells with higher rate of metabolism more than supporting stromal cells.
• Functional and morphologic changes are reversible if the damaging stimulus is removed.

Irreversible Cell Injury

• Irreversible damage is caused by severe injurious agents over a long duration.
• Irreversible damage includes Necrosis or Apoptosis (single cell death).

Reversible Cell Injury: Cloudy Swelling and Hydropic Degeneration

• Mild and excessive (in hydropic) intracellular water accumulation.
• Triggered by mild injury of short duration.
• Occurs in organs rich in mitochondria, such as renal tubules (mostly proximal convoluted tubules), cardiac muscles, and hepatocytes.

Pathogenesis of Cloudy Swelling and Hydropic Degeneration

• Mitochondrial function is disrupted first, leading to decreased ATP,
• This causes an increase in intracellular sodium and lactic acid.
• The increase in cytoplasmic osmotic pressure helps intracellular water accumulation, leading to cell swelling.

Morphology of Cloudy Swelling and Hydropic Degeneration

• Grossly, the affected organ appears swollen, soft, bloodless, and pale due to compression of the capillaries by the swollen cells.
• The outer surface is smooth with a tense capsule and rounded borders.
• The cut surface appears cloudy (less glistening), opaque, and bulges outwards.
• Microscopically; In cloudy swelling, the cells are swollen with compressed capillaries, the nucleus is normal, and the cytoplasm is granular.
• Microscopically, In hydropic degeneration, the cells are swollen with compressed capillaries, the nucleus is normal, and the cytoplasm is pale and shows multiple vacuoles.

Fatty Change (Steatosis) - Definition

• Reversible cell injury characterized by the accumulation of neutral fat in functioning cells.

Causes of Fatty Change

• Hypoxia.
• Bacterial toxins of acute and chronic infections.
• Chemical agents such as alcohol, phosphorus, and carbon tetrachloride.

Morphology of Fatty Change

• Grossly, the affected organ appears swollen, soft, and pale yellow.
• The outer surface is smooth with a tense capsule and rounded borders.
• The cut surface appears yellow, bulges outwards and is greasy to the touch.
• Microscopically, the cells appear swollen and show multiple tiny cytoplasmic vacuoles.
• Fat globules can fuse together, forming a big globule that pushes and flattens the nucleus against the cell membrane, giving the cell a signet ring appearance.
• Swollen cells compress the intercellular capillaries.
• Fat special stains are done on frozen sections.

Fat Stains

• During routine staining of sections (Hx and E), fat is dissolved during preparation.
• For demonstration of fat, frozen sections are used and stained by
  • Sudan III and oil red O to give an orange-red appearance
  • Osmic acid to give a Black appearance.