Homeostasis, feedback mechanism,cellular adaptations cell injry..etiology...types and its pathogenesis.. morphology of cellinjury necrosis calcification

1. CELL INJURY
AND
CELLULAR ADAPTATIONS

3. HOMEOSTASIS
• It is the condition of equilibrium in the body’s internal
environment due to constant interaction of body’s regulatory
processes.
• It is a dynamic condition.
• In response to changing condititions, body’s equlibrium will
shift to a narrow range which is compatable with maintaining
life.
• An important aspect of homeostasis is maintaining the
volume and composition of the body fluids.

4. CONTROL OF HOMEOSTASIS
• Disruptions in homeostasis come from the external
environment in the form of physical insults (from internal
environment) and from psychological stresses.
• Most cases, the disruptions in homeostasis is mild and
temporary and in other cases, it is intensed and prolonged.
• The body has many regulatory systems which bring the
homeostasis back to normal condition.
• These include endocrine system and nervous system.

5. FEEDBACK SYSTEMS
• It is the cycle of events in which the status of the body
condition is monitored, evaluated, changed, remonitored and
re-evaluated.
• Each monitored variable, such as blood pressure, blood
temperature and blood glucose, is called controlled
condition.
• Any disruptions that change the controlled condition is called
stimulus.

6. COMPONENTS OF FEEDBACK SYSTEMS
It consists of three components:
• Receptor
• Control centre
• Effector
Receptor :
• It is the body structure that monitors the controlled condition
and sent input to the control centre.
• The input is in the form of nerve impulses and chemical
signals.

7. Control centre:
• It sets the range of values within which a controlled condition
should be maintained, evaluates the input it receives from the
receptors, and sent output whenever needed.
• Output is in the form of nerve impulses, hormones, etc.
Effector:
• It is a body structure which receives the output from the control
centre and produces effect that changes the controlled
condition.
• Nearly every organ or tissue in the body can act as effectors.

8. TYPES OF FEEDBACK SYSTEMS
NEGATIVE FEEDBACK :
• It reverses a change in controlled condition.
• Eg : Homeostatic regulation of Blood pressure.
POSITIVE FEEDBACK
• It strengthens or reinforces the input.
• Eg: Positive feedback control of labor contractions during
pregnancy.

9. CELLULAR ADAPTATIONS
For the sake of the survival on exposure to stress, the cells make
adjustments in their environment to
•Physiological needs: Physiologic adaptation
•Non – lethal pathologic injury : Pathologic adaptation

14. PATHOLOGIC FEATURES:
• There is enlargement of the affected organs or tissue and
increase in the number of cells.
• This is due to the increased rate of DNA synthesis and hence
increased mitosis of the cells.

19. MORPHOLOGIC FEATURES:
• The affected organ is enlarged and heavy.
• Eg: A hypertrophied heart of a patient with systemic
hypertension may weigh 700-800mg as compared to average
normal adult weight of 350mg.
• There is enlargement of muscle fibres and nuclei.
• At ultrastructural level, there is increased synthesis of DNA
and RNA, increased protein synthesis and increased number
of organelles like mitochondria, endoplasmic reticulum and
myofibrils.

25. MORPHOLOGIC FEATURES:
• Organ is small, often shrunken.
• The cells become smaller in size, but not dead cells.
• Shrinkage is due to reduction in cell organelles, chiefly
mitochondria, myofilaments and endoplasmic reticulum.
• There is often increase in the number of autophagic vacuoles
containing cell debris. These autophagic vacuoles may persist
to form ‘residual bodies’ in the cell cytoplasm.

32. CELL INJURY

34. CAUSES OF CELL INJURY
The main causes of cell injury includes:
• Genetic causes
• Acquired causes
GENETIC CAUSES
1. Developmental defects:
• It includes fetal abnormalities arising due to effect in morphogenesis.
• It leads to:
 Intrauterine death
 Intrauterine growth retardation
 Functional defects
 Malformation
• The clinically important examples include:
 Thalidomide malformations
 Fetal alcohol syndrome

35. 2. Karyotypic defects:
• The photographic representation of chromosomes obtained on
staining is called karyotype.
• Chromosomal abnormalities mainly are of two types:
a) Numerical abnormalities:
It includes
 Polyploidy
 Down’s syndrome
 Kleinfelters syndome
b) Structural abnormalities
It includes
 Deletions
 Inversions
 Ring chromosome

38. PATHOGENESIS OF REVERSIBLE CELL INJURY
The biochemical mechanisms responsible for cell injury includes:
• Depletion of ATP
• Mitochondrial damage
• Influx of intracellular Calcium
• Defects in membrane permeability
• Reactive oxygen species

39. DEPLETION OF ATP

40. MITOCHONDRIAL DAMAGE

41. INFLUX OF INTRACELLULAR CALCIUM

42. DEFECTS IN MEMBRANE PERMEABILITY

43. REACTIVE OXYGEN SPECIES
• Cells generate oxygen by reducing molecular oxygen to water.
• During this process, small amount of partially reduced
reactive oxygen forms are produced.
• The generated free radical will further propagate the reaction.
• Imbalance between free radical generating and radical
scavenging system results in oxidative stress.

44. FREE RADICALS MAY BE INITIATED WITHIN CELLS IN SEVERAL WAYS
• Absorption of radiant energy.
• Enzymatic metabolism of exogenous chemicals or drugs.
• The reduction-oxidation reactions that occur during normal
metabolic processes.
• Transition metals such as Iron and Copper donate or accept free
electrons during intracellular reactions and catalyze free radical
formation.
• Nitric oxide (NO), an important chemical mediator can act as a free
radical.

45. Three reactions of reactive species are particularly relevant to
cell injury:
• Lipid oxidation of membranes
• Oxidative modification of proteins
• Lesions in DNA

49. • Several enzymatic and non enzymatic systems that contribute
to inactivation of free radical reactions.
• Enzymes: catalase, superoxide dismutase, glutathione
peroxidase.
• Antioxidants (non –enzymes): Vitamin A and E, ascorbic acid,
glutathione
• The final effects induced by the free radicals depends on net
balance between free radical formation and termination.

50. PATHOGENESIS OF IRREVERSIBLE CELL INJURY

51. MORPHOLOGY OF CELL INJURY
MORPHOLOGY OF REVERSIBLE CELL INJURY
Following are the morphologic forms of the reversible cell injury:
• Hydropic change
• Hyaline change
• Mucoid change
• Fatty change

52. Hydropic change (cloudy swelling/ vacuolar degeneration) : It is
the accumulation of water in the cytoplasm of the cell.
ETIOLOGY Acute and Sub acute cell injury from
•Bacterial toxins, chemicals, poisons, high fever, burns
•Intravenous administration of hypertonic glucose/saline
PATHOGENESIS •Impaired regulation of sodium and potassium in membrane
•Intracellular accumulation of sodium and escape of potassium
•Rapid flow of water and calcium inside the cell
•Cellular swelling occurs
MORPHOLOGY Macroscopically :
The affected organ such as kidney, liver, pancreas or heart muscle is
enlarged due to swelling.
Microscopically :
•Cells are swollen and the microvasculature compressed.
•Small clear vacuoles are seen in the cells.
•Small cytoplasmic blebs may be seen.
•Nucleus appears pale.

53. Hyaline change (Hyaline = glassy)
• It is a descriptive term for glassy, homogenous, eosinophilic
appearance of material in hematoxylin and eosin stained
sections.
• It may be intracellular or extracellular.
INTRACELLULAR HYALINE EXTRACELLULAR HYALINE
Seen in epithelial cells. Seen in connective tissues.
•Hyaline droplets in PCT (excess absorption
of plasma proteins)
•Hyaline degeneration of rectus abdominalis
(Zenker’s degeneration) in typhoid fever.
•Mallory’s hyaline aggregates of
intermediate filaments in hepatocytes in
alcoholic cell injury.
•Russel’s bodies representing excessive
Immunoglobulins in RER of plasma cells.
•Hyaline degeneration in leiomyomas of
the uterus.
•Hyalinised old scar of fibrocollagenous
tissue.
•Hyaline arteriosclerosis in renal vessels
in HTN and DM.
•Hyalinised glomeruli in chronic
glomerulonephritis.

54. Mucoid change:
• Mucus is a combination of proteins and mucopolysaccharides
• Secreted by mucous glands and mucin is its main constituent.
• Mucin is secreted by epithelial cells of mucous membranes
and glands, as well as by some connective tissues like in
umbilical cord.
EPITHELIAL MUCIN CONNECTIVE TISSUE MUCIN
•Catarrhal inflammation of mucus
membranes in respiratory tract, uterus.
•Obstruction of duct leading to mucocele
in oral cavity.
•Cystic fibrosis of pancreas.
•Mucin secreting tumors in stomach,
ovary, etc.
•Mucoid or myxoid degeneration in some
tumors
•Dissecting aneurysm of the aorta
•Myxomatous change in dermis in
Myxoedema.
•Myxoid change in the synovium in
ganglion on the wrist.

55. Fatty change(steatosis)
• Intracellular accumulation of fat within the parenchymal cells.
• The deposit is in the cytosol and represents an absolute increase in
the intracellular lipids.
• It is especially common in liver, heart, kidneys and other skeletal
muscles.
Fatty liver
• Liver is the commonest site for the accumulation of fat as it is the
site of lipid metabolism.
• Depending upon the cause and amount of accumulation, fatty
change may be
mild and reversible
Severe and irreversible

56. Etiology:
Two types of causes:
Condition with excess fat
(hyperlipidemia)
•Obesity
•Diabetes mellitus
•Congenital hyperlipidemia
Liver cell damage •Alcoholic liver disease
•Starvation
•Protein calorie malnutrition
•Chronic illnesses eg.Tuberculosis
•Hypoxia eg. Anemia, Cardiac failure
•Hepatotoxins
•Drug induced liver injury

57. Pathogenesis
Normal lipid metabolism

58. In fatty liver, intracellular accumulation of triglycerides can occur
due to defect in following mechanisms like
• Increased entry of free fatty acids into the liver.
• Increased synthesis of fatty acids by the liver.
• Decreased conversion of fatty acids into ketone bodies.
• Increased α- glycerophosphate causing increased conversion of fatty
acids to triglycerides.
• Decreased synthesis of lipid acceptor protein resulting in decreased
formation of lipoproteins.
• Block in the excretion of lipoprotein from the liver into plasma.

59. Morphology
• Macroscopically, the liver in fatty change is enlarged with a
tense, glistening capsule and rounded margins.
• Microscopically,
 The vacuoles are initially small and present around the
nucleus.
 But with progression of the process, the vacuoles becomes
larger pushing the nucleus to the periphery of the cell.
 At times, the hepatocytes with large lipid vacuoles may
rupture and lipid vacuoles coalesce to form fatty cysts.

60. Morphology of Irreversible cell injury
(CELL DEATH)
Autolysis (self digestion)
• It is the disintegration of cell by its own hydrolytic enzymes liberated from
lysozymes.
• It can occur in the living body when it is surrounded by inflammatory reaction.
• It is
 Rapid in pancreas, gastric mucosa(rich in hydrolytic enzyme)
 Intermediate in tissues like heart, liver and kidney
 Slow in fibrous tissue.
• Morphology : homogenous and eosinophilic cytoplasm with loss of cellular
details and remains of cell as debris.

61. NECROSIS
• It is defined as the localised area of death of tissue followed by
degradation of tissue by hydrolytic enzymes liberated from the
dead cells; it is accompanied by inflammatory reaction.
• Necrosis can be caused by various agents such as hypoxia, chemical
and physical agents, microbial agents, etc.
• Two essential changes occurred are:
1. Cell digestion by lytic enzymes: Morphologically identified as
homogeneous and intensely eosinophilic cytoplasm. Occasionally
shows dystrophic calcification and cytoplasmic vacuolation

62. 2. Denaturation of proteins:
• Morphologically seen as nuclear changes in necrotic cell.
• These nuclear change may include
Pyknosis ( condensation of nuclear chromatin)
Karyolysis (dissolution of chromatin fibres)
Karyorrhexis (fragmentation of nucleus)

64. TYPES OF NECROSIS
1. COAGULATIVE NECROSIS
• Most common type of necrosis caused by irreversible focal injury, mostly
from ischemia and often from bacterial and chemical agents.
• The mostly affected are heart, kidneys and spleen
Microscopically •Early stage : Pale, Firm and slightly swollen
•Later : yellowish, softer and shrunken
Macroscopically •Converted to tombstone
•The outline of the cells are retained so that the
cell type can still be recognized but their
cytoplasmic and nuclear details are lost.

65. 2. LIQUEFACTION NECROSIS
• Caused due to ischemia and often from bacterial and chemical agents.
• It occurs due to degradation of tissue by the action of powerful hydrolytic
enzymes
• Common examples are infarct brain and abscess cavity
Microscopically •Early stage :soft with liquefied centre containing
necrotic debris.
•Later :cyst wall formed
Macroscopically •The cystic space contains necrotic cell debris and
macrophages filled with phagocytosed material.
•The cyst wall is formed by proliferating
inflammatory cells, capillaries in case of brain and
proliferating fibroblasts in case of abscess cavity.

66. 3. CASEOUS NECROSIS : Found in the centre of foci of tuberculous infections
and is combined feature of both liquefactive and coagulative necrosis.
Microscopically •Resembles dry cheese.
•Soft, granular and yellowish.
Macroscopically •The necrosed foci are structureless, eosinophilic
and contain granular debris.
4. FIBRINOID NECROSIS
•It is characterized by deposition of fibrin like material has staining property of
fibrin and is found in arterioles in HTN, peptic ulcer, etc
Microscopically •Brightly eosinophilic, hyaline like deposition in the vessel
wall.
•Necrotic foci is surrounded by nuclear debris of neutrophils
•Local hemorrhage may occur.

67. 5. FAT NECROSIS
• It is a special form of cell death occurring at two anatomically different
locations but morphologically similar lesions.
• Fat necrosis hydrolyses fat present in adipose tissue to glycerol and free fatty
acids. The damaged adipose tissue assume cloudy appearance. The leaked
out fatty acids combine with calcium to form calcium soaps.
Microscopically •Yellowish-white and firm deposits
•Formation of Calcium soaps imparts firmer and chalky
white appearance.
Macroscopically •The necrosed fat cells have cloudy appearance and are
surrounded by inflammatory reaction.
•Calcium soaps are seen as amorphous, granular and
basophilic material.