patoloji-ders-notlari

Title

Serdar Balcı

Cellular Responses to Stress and Injury

Serdar BALCI

Adaptations

• Reversible changes in respone to environment
• Changes in:
  • Number
  • Size
  • Phenotype
  • Metabolic activity
  • Functions

Physiologic

Pathologic

• Normal stimulation

  • Hormones
  • endogenous chemical mediators

• Uterus in pregnancy

• Breast in lactation

• Stress

  • allow cells to modulate their structure and function
  • escape injury

• Response to pathology (as a protective mechanism)

• Pathologic itself

Hypertrophy

Hyperplasia

Atrophy

Metaplasia

Hypertrophy

• Increase in size of cells
• Which causes increase in organ size
• Caused by
  • Increased functional demand
    • Skeletal muscle, hearth
  • Growth factor or hormonal stimulation
    • Breast during pregnancy

Physiologic

Pathologic

Physiologic hypertrophy

Physiologic hypertrophy and hyperplasia of the uterus during pregnancy

Pathologic hypertrophy

Atlas of Autopsy Pathology, 2 nd __ ed. Figure 15-33 Left ventricular hypertrophy. The short-axis plane of section shows the cavities and entire circumference of the ventricular walls to good advantage. In this patient with hypertension, the left ventricular cavity is small because of concentric hypertrophy of the walls and papillary muscles.__

Atlas of Autopsy Pathology, 2 nd __ ed. __ Figure 15-34 *   Right ventricular hypertrophy. These short-axis cuts of the heart from an adult with a congenital ventricular septal defect show the right ventricular hypertrophy and marked cavity dilation that are associated with long-standing pulmonary hypertension. In the normal heart, the right ventricular apex does not quite reach the apex of the heart, so in this specimen the apical cut (top) is particularly revealing. The left ventricle is relatively normal. ** *RV, __ Right ventricle; __ LV, __ left ventricle. __

Atlas of Autopsy Pathology, 2 nd __ ed. __ Figure 15-35    Concentric and eccentric hypertrophy. The difference between concentric hypertrophy and eccentric hypertrophy is illustrated in these two short-axis cuts from two different hearts of approximately the same weight ( left, __ 575 g; __ right, __ 600 g). In the specimen on the left, the left ventricular cavity __ (LV) __ is dilated and the walls appear nearly normal in thickness. In contrast, the heart on the right has very thick left ventricular walls that diminish the cavity. Both specimens showed histopathologic features of hypertrophy. __

Atlas of Autopsy Pathology, 2 nd __ ed. __ Figure 15-37 **   Right ventricular hypertrophy and dilation. Normally, the right ventricular apex does not quite reach the apex of the heart. This apical cut of a heart from a patient with chronic liver disease shows the right ventricular cavity, consistent with pulmonary hypertension. **

Mechanisms of Cardiac Hypertrophy

• mechanical triggers
  • Stretch
  • increase in the amount of blood volume
  • Push blood to a resistant channel
• trophic triggers
  • Growth factors
  • Adrenergic hormones

mechanical triggers

trophic triggers

Induction of genes

Production of proteins

more proteins and myofilaments per cell

more proteins and myofilaments per cell

increases the force generated with each contraction

meet increased work demands

So, we are happy

Mechanisms of Cardiac HypertrophyThings start to change

switch of contractile proteins from adult to fetal or neonatal forms

α-myosin heavy chain is replaced by the β form of the myosin heavy chain, which produces slower, more energetically economical contraction

• Then it reaches the limit
• Muscle mass cannot compansate the burden
• Large proteins are likely to pump less effectively
• Degenerative changes start
  • Fragmantation
  • Loss of fibrillary elements

Maybe the vessels are not enough

Mitochondria cannot supply ATP properly

**The synthesis of new proteins are not effective **

Mechanisms of Cardiac HypertrophyEnd up with

Huge, dilated

So called “bovine hearth”

Cannot pump enough

Even cannot pump enough to supply itself

Cell injury

A vicious circle

Adaptations

Hypertrophy

Hyperplasia

Atrophy

Metaplasia

Hyperplasia

increase in cell number

adaptive response in cells capable of replication

Hypertrophy and hyperplasia can occur together

Physiologic hypertrophy and hyperplasia of the uterus during pregnancy

physiologic hyperplasia

Hormonal Hyperplasia

Compensatory hyperplasia

Female breast

Puberty, pregnancy

proliferation of the glandular epithelium

Residual tissue growth

After removal or partial loss of organ

Liver

Compensatory Hyperplasia of Liver

One can donate part of liver when (s)he is alive

Mitosis starts 12 hours later

Restore liver to original weight

Then proliferation stops

Examples of pathologic hyperplasia

• Endometrial hyperplasia
  • Disturbance of the hormonal balance in favor of estrogen over progesterone

Hyperplasia in wound healing

Fibroblasts, blood vessels proliferate

Local effect of mediators from leukocytes

Hyperplasia in viral infection

• **Papillomaviruses **
  • cause skin warts and mucosal lesions
  • __ masses of hyperplastic epithelium. __
• Growth factors may be encoded by viral or infected host cell genes.

Hyperplasia

The hyperplastic process remains controlled; if the signals that initiate it abate, the hyperplasia disappears

In cancer, in which the growth control mechanisms become dysregulated or ineffective in many cases

Pathologic hyperplasia constitutes a fertile soil in which cancers may eventually arise

Hypertrophy vs Hyperplasia

Hypertrophy

Hyperplasia

increase in the size of cells

increase in the size of the organ

no new cells, just bigger cells

increased amount of structural proteins and organelles

when cells are incapable of dividing

• increase in cell number
• adaptive response in cells capable of replication
  • (remember G0,G1,S,M phases of mitosis)

Adaptations

Hypertrophy

Hyperplasia

Atrophy

Metaplasia

Atrophy

Shrinkage in the size of the cell

by the loss of cell substance

After many cells become atrophic tissue and organs become atrophic

Cells decrease function, not dead

Normal brain of a young adult

an 82-year-old man with atherosclerotic disease.

Atrophy of the brain is due to aging and reduced blood supply

Causes of atrophy

• decreased workload
  • immobilization of a limb after fracture
• loss of innervation
• diminished blood supply
• inadequate nutrition
• loss of endocrine stimulation
• aging (senile atrophy)

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Physiologic atrophy

Pathologic atrophy

• Decrease in size of uterus
  • Decrease hormones after menopouse

Denervation atrophy

Cellular changes are same

Cells get smaller until a point where survival is still possible

Mechanism of atrophy

Decreased protein synthesis

Increased protein loss

Reduced metabolic activity

ubiquitin-proteasome pathway

Nutrient deficiency and disuse activate process

Increased catabolism

Adaptations

Hypertrophy

Hyperplasia

Atrophy

Metaplasia

Metaplasia

• reversible change
• one adult cell type
  • epithelial or mesenchymal)
• replaced by another adult cell type

Question to think aboutWhich one is pathologic?

Hormonal Hyperplasia

Hormonal hyperplasia

Female breast

Increased prolactin in circulation

Puberty, pregnancy

proliferation of the glandular epithelium

Male breast

Increased prolactin in circulation

Reason is usually prolactin secreting pituitary tumor

Acini are not present in male breast. Ductules and stroma is affected.

Question to thinkWhich one is pathologic inCompensatory Hyperplasia of Liver

Hyperplasia after donation

Regenerative nodules in cirrhosis

One can donate part of liver when (s)he is alive

Mitosis starts 12 hours later

Restore liver to original weight

Then proliferation stops

3D architecture is preserved

After cirrhosis occurs

Functional liver cells required

Liver cells are capable of dividing

They start to divide to compansate

Cannot reform the 3D architecture of liver

Question to think aboutDoes brain gets hyperplastic/hypertophic changes?

No

Yes

With ongoing learning stimuli new connections are being made

Brain has ability to plasticize

Nerve cells are stabile

They do not proliferate

They do not increase in size