1. Cellular Adaptation: Pathophysiology Wanda Lovitz, MSN, APRN The cell is the fundamental unit of disease

2. Objectives: Cellular Adaptation  Cite the general purpose of changes in cell structure and function that occur as the result of normal adaptive processes.  Describe cell changes that occur with atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia, anaplasia, and neoplasia.  Cite three sources of intracellular accumulations.  Differentiate between the effects of ionizing and non-ionizing radiations.  State how biological, physical, and chemical agents injury cells.  Describe cell changes that occur with ischemia and hypoxic cell injury.  Cite the reasons for the changes that occur with wet, dry, and gas gangrene.

3. Cellular Adaptation Permits survival and maintenance of cell function Permits survival and maintenance of cell function May alter differentiation of genes enabling a cell to change size or form. May alter differentiation of genes enabling a cell to change size or form. Is a normal adaptive response to an appropriate stimulus Is a normal adaptive response to an appropriate stimulus Abnormal cellular changes may also occur Abnormal cellular changes may also occur

4. (cells shrink) Atrophy (cells shrink) D/t  workload or adverse D/t  workload or adverse environmental conditions Is adaptive and reversible Is adaptive and reversible results in a decrease in cell size results in a decrease in cell size Types Types Disuse atrophy (paralysis) Disuse atrophy (paralysis) Degeneration atrophy (MS) Degeneration atrophy (MS) Ischemic atrophy (kidney, heart) Ischemic atrophy (kidney, heart) Malnutrition atrophy (starvation) Malnutrition atrophy (starvation) Loss of endocrine stimulation (uterine, breast) Loss of endocrine stimulation (uterine, breast) Bilateral Atrophy Unilateral

5. Brain atrophy (Brain atrophy with Alzheimer's) - Atrophic cells have lost endoplasmic reticulum, have fewer mitrochrondria, and myofliaments. Research has shown we are less likely to loose brain function if we continue to engage all parts of the brain

6. HYPERTROPHY  D/T  workload requirement of an organ part cell size & cell function  Causes an increase in cell size & cell function  *See  protein in cellular components with no  in cellular fluid  Results in an increase in tissue mass   Seen in cardiac, skeletal, and muscle tissue  These cells are not capable of mitosis (so, no  number or hyperplasia)  May be a normal physiologic response  as seen in an increase in muscle size with exercise (  size of cells)

7. HYPERTROPHY May be a pathological response as in myocardial hypertrophy from HTN or valve disease May be a pathological response as in myocardial hypertrophy from HTN or valve disease Example: Left ventricular hypertrophy (LVH) – Example: Left ventricular hypertrophy (LVH) – A HYPERTROPHY resulting in  size of heart d/t  workload caused by HTN. A PATHOLOGICAL HYPERTROPHY resulting in  size of heart d/t  workload caused by HTN. There is an increase in size but function is compromised There is an increase in size but function is compromised However, there is a LIMIT to the amount the tissue can enlarge However, there is a LIMIT to the amount the tissue can enlarge Left Ventricular Hypertrophy LVH) – seen with poorly controlled HTN Myocardial cells enlarge d/t  workload of pumping

8. HYPERPLASIA (  # of cells) Occurs d/t to a response from appropriate stimulus and ceases when stimulus is removed Occurs d/t to a response from appropriate stimulus and ceases when stimulus is removed An increase in NUMBER of cells An increase in NUMBER of cells Restricted to cells capable of mitosis Restricted to cells capable of mitosis epidermis, intestinal epithelium, and glandular tissue. epidermis, intestinal epithelium, and glandular tissue. Physiological hyperplasia Physiological hyperplasia uterus and breast enlarge in pregnancy uterus and breast enlarge in pregnancy

9. HYPERPLASIA (cont) May be a PHYSIOLOGICAL response and occur with hypertrophy (  in both cell size & number) May be a PHYSIOLOGICAL response and occur with hypertrophy (  in both cell size & number) Hyperplasia is important in wound healing Hyperplasia is important in wound healing May also be a non-physiologic hyperplasia May also be a non-physiologic hyperplasia Seen in prostatic hypertrophy (BPH), endometrial hyperplasia d/t increased hormone stimulation, or thyroid enlargement Seen in prostatic hypertrophy (BPH), endometrial hyperplasia d/t increased hormone stimulation, or thyroid enlargement Benign Prostatic Hypertrophy/Hyperplasia (BPH) – can cause difficulty with urination Goiter – thyroid hyperplasia

10. Hyperplasia seen in finger warts: epidermal hyperplasia d/t viral stimulation Plantar warts -  in # of epidermal cells Verrucae vulgaris – common warts (  DNA synthesis and mitotic division)

11. METAPLASIA  One cell type is replaced by another  May predispose to cancer  Involves reprogramming of undifferentiated stem cells  Allows to cells to better survive in a hostile environment  Is REVERSIBLE  Is a response to chronic irritation and inflammation

12. METAPLASIA Cells that are normally columnar or stratified may change tosquamous. Cells that are normally columnar or stratified may change to squamous. Examples: Examples: With continued smoke exposure, ciliated columnar cells are changed to stratified squamous cells With continued smoke exposure, ciliated columnar cells are changed to stratified squamous cells Cervical cells change when exposed to STDs or HPV Cervical cells change when exposed to STDs or HPV Think metamorphosis or change from one form to another Think metamorphosis or change from one form to another Continued exposure may predispose to cancerous transformations. Continued exposure may predispose to cancerous transformations. Stratifiied squamous cells Ciliated columnar cells

13. DYSPLASIA DYSPLASIA * (ATYPICAL HYPERPLASIA ) Deranged cell growth resulting in cells of varying size, shape, and appearance Deranged cell growth resulting in cells of varying size, shape, and appearance May be associated with chronic irritation or inflammation May be associated with chronic irritation or inflammation May be reversible if offending agent is removed May be reversible if offending agent is removed Dysplasia is considered A STRONG PRECURSOR OF CANCER!!! Example: Cervical dysplasia However, dysplasia is an adaptive process – may or may not lead to cancer However, dysplasia is an adaptive process – may or may not lead to cancer Decrease risk if irritation is removed or inflammation treated.

14. Anaplasia Cells differentiate to a more or embryonic form. Cells differentiate to a more IMMATURE or embryonic form. Malignant tumors are characterized by anaplastic cell growth. Malignant tumors are characterized by anaplastic cell growth. Ovarian cancer cells dividing

15. Summary: Cellular Changes Then anaplasia/neoplasia 

16. CELLULAR ACCUMULATIONS *(cellular infiltrations) Is a buildup of substances the cells are unable to dispose of Is a buildup of substances the cells are unable to dispose of Is a result of cell injuries Is a result of cell injuries Examples Examples Carbon/coal dust Carbon/coal dust Lipids Lipids Fluid/edema Fluid/edema

17. Cellular Infiltrations carbon, triglycerides Carbon can accumulate via inhaled coal dust. Can cause black lung disease (pneumonconiosis) Carbon can accumulate via inhaled coal dust. Can cause black lung disease (pneumonconiosis) Organs enlarged, i.e., Organs enlarged, i.e., “ MEGALY” Ex. spleenomegaly, hepatomegaly Ex. spleenomegaly, hepatomegaly Diseases d/t cellular accumulations MAY BE REVERSIBLE if d/t a correctable systemic disorder Diseases d/t cellular accumulations MAY BE REVERSIBLE if d/t a correctable systemic disorder Example: elevated triglyceride levels can result in a “FATTY” liver. Example: elevated triglyceride levels can result in a “FATTY” liver. This may reverse when triglyceride level is lowered with medication This may reverse when triglyceride level is lowered with medication hepatomegaly

18. CELLULAR ACCUMULATIONS: lipids and edema If the offending cause is not or cannot be corrected If the offending cause is not or cannot be corrected CELL DEATH may occur CELL DEATH may occur Example: Example: Abnormal lipids in the brain of child with Tay-Sachs disease (a genetic disorder) ultimately results in cell death, and a shortened life span. Abnormal lipids in the brain of child with Tay-Sachs disease (a genetic disorder) ultimately results in cell death, and a shortened life span. cellular swelling – extracellular water shifts into cells cellular swelling – extracellular water shifts into cells Cerebral edema

19. *Causes of cell injury Chemical agents Chemical agents Hypoxia Hypoxia Free radicals Free radicals Infectious agents (bacteria, viruses, fungi) Infectious agents (bacteria, viruses, fungi) Physical and mechanical agents Physical and mechanical agents Genetic factors Genetic factors Nutritional imbalances Nutritional imbalances **Individuals have different abilities to adapt to these stressors **Individuals have different abilities to adapt to these stressors

20. What are Free Radicals? Free radical – atoms or groups of atoms with an odd (unpaired) number of electrons Free radical theory of aging states that organisms age because cells accumulate free radical damage over time Antioxidants are believed to protect against free radical damage Some free radicals are formed during normal metabolism

21. CELLULAR INJURY  Cause: Mechanical Forces  Cellular injury may be reversible or irreversible determined by: the severity of the insult, blood supply, nutritional status, and regeneration capability  Physical Agents – trauma  Electrical  Temperature extremes  Radiation

22. Mechanical Injury: Physical Agents Cause: Physical Agents Mechanical forces such as physical trauma resulting in lacerations, fractures, burns, injury to blood vessels, and disruption in blood flow. Compound fracture laceration

23. Mechanical force injury: Electrical  Can cause extensive tissue injury and disruption of neural and  Can cause extensive tissue injury and disruption of neural and cardiac impulses  Vessels degenerate and create thrombi or clots  The body acts as a conductor of electrical current. Can see seizures or cardiac arrhythmias  Extent of injury determined by the amount of voltage and duration of exposure.  Lightning and high voltage wires produce most severe damage.

24. Mechanical force injury: Temperature extremes  Heat stroke or partial-thickness burns cause cellular injury  With an increase in intensity of heat, blood vessels coagulate and tissue protein loss occurs  Fried egg effect  Cold exposure increases blood viscosity and induces vasoconstriction which may cause tissue hypoxia  Disrupts the cell membrane

25. Mechanical force injury: Ultraviolet Radiation  Sunburns increase the risk of skin cancers  Damage to melanin-producing processes in skin and damage to DNA occurs  Risk of skin cancers  with number and severity of sunburns  Average 20 years from exposure to development of skin cancer

26. Radiation injury: Ionizing radiation  Direct injury causes immediate cell death or deranged replication  The endothelial cells in blood vessels are very sensitive Radiation dermatitis stomatitis

27. Radiation Injury  Ionizing radiation Chronic effect causes scarring or fibrosis Most radiation injury is d/t localized irradiation used to treat cancer Effects DNA synthesis and interferes with mitosis Bone marrow and intestines are very vulnerable to radiation exposure

28. Mechanical force: Chemical Injury Cells may be damaged by a vast array of chemicals Cells may be damaged by a vast array of chemicals A biochemical interaction between a toxic substance and the cell’s plasma membrane occurs and leads to  cell permeability A biochemical interaction between a toxic substance and the cell’s plasma membrane occurs and leads to  cell permeability Examples Examples air and water pollution tobacco smoke some processed or preserved foods carbon monoxide insecticides trace metals such as lead, and DRUGS

29. Chemicals in tobacco smoke

30. Tylenol/acetaminophen can cause chemical injury to cells. The cells in which organ are most affected by Tylenol?  Kidney  Brain  Liver  Heart

31. Chemical injury: Drugs  May damage cells directly or indirectly  Both prescription (RX) and over-the-counter (OTC) medication can cause cell damage.  Tylenol can damage liver cells  Ibuprofen can injure kidney cells  ETOH can harm gastric mucosa (gastritis) and liver cells and harm the developing fetus  Fetal Alcohol Syndrome ↔

32. Chemical injury: Drugs  Anti-cancer drugs can directly injure normal cells  Some drugs produce metabolic end-products that are toxic to the cells  Example:  Tylenol, which is detoxified in the liver, can cause massive liver necrosis when taken in large amounts

33. Lead paint tastes good.  True  False

34. Chemical injury: Lead Toxicity Lead is very toxic to the cells Sources include: flaking paint, lead-contaminated dust and soil, lead- contaminated root vegetables, lead water pipes, and newsprint Inhaled or ingested lead accumulates over time Lead is absorbed via the GI tract or via the lungs into the blood Lead is absorbed via the GI tract or via the lungs into the blood Lead is toxic d/t multiple biochemical effects: Lead is toxic d/t multiple biochemical effects: RBC’s become small and pale RBC’s become small and pale (anemia) Since lead is excreted by the kidneys, kidney damage leading to can occur Since lead is excreted by the kidneys, kidney damage leading to renal failure can occur

35. Lead (cont)  Lead causes demyelination of NERVE CELLS in the cerebral and cerebellar matter  causing death of neural and cortical cells  Lead toxicity can cause  a decrease in IQ  impaired neurobehavioral development in children  In adults see peripheral neuropathy

36. Injury from biological agents: viruses, bacteria, and parasites Biological agents are able to replicate and thus can continue to cause injury to cells Biological agents are able to replicate and thus can continue to cause injury to cells Viruses incorporate themselves into the DNA of the cell Viruses incorporate themselves into the DNA of the cell Bacteria secrete exotoxins or endotoxins that interfere with cellular reproduction of ATP, or release antitoxins that cause injury Bacteria secrete exotoxins or endotoxins that interfere with cellular reproduction of ATP, or release antitoxins that cause injury Parasites can cause direct injury to the cell Parasites can cause direct injury to the cell salmonella bacteria virus

37. Injury from nutritional imbalances  Nutritional excesses such as obesity and diets high in fats can predispose to atherosclerosis leading to ischemia  The body needs minerals, vitamins, certain fatty acids, and specific amino acids.  Nutritional and vitamin deficiencies interfere with cell metabolism and delay wound healing Infected decubitus ulcer 

38. Hypoxic/Ischemia Cell Injury *(the most common cell injury)  Hypoxic injury  Generalized  Is an inadequate supply of O2 in BLOOD affecting the entire body.  Sx include change in LOC, confusion, combativeness  Low pulse oximetry (less than 90%)  Localized  Causes ischemia of TISSUES  If not corrected, can see infarction or death of tissues ( heart, renal)  Ischemia affects local tissue and is reversible  Sx include pain, cyanosis,weak or absent pulses  Infarction is tissue death and is not reversible.

39. (cont) Hypoxic injury (cont)  The cell reverts to anaerobic metabolism causing a fall in PH  lactic acid accumulates in the cell  lactic acidosis  Causes of hypoxia Decrease of oxygen in the air Respiratory disease Ischemia Anemia d/t  hemoglobin Edema

40. Cellular Death Apopthosis Apopthosis Is essentially “cell suicide” or programmed cell death Is essentially “cell suicide” or programmed cell death Apopthosis is the process that eliminates: Apopthosis is the process that eliminates: Worn out cells (RBCs) Worn out cells (RBCs) Cells which have been produced in excess Cells which have been produced in excess ex. WBCs with infectious response/hepatocytes with hepatitis) Cells which have developed improperly Cells which have developed improperly ex. spontaneous abortion Cells which have genetic damage Cells which have genetic damage Ex cancer

41. Necrosis  Interferes with cell replacement and tissue regeneration.  Necrotic cells or tissue can:  Liquefication  cells  cells becomes liquefied  Ex: abcess, brain tissue  May result in wet gangrene  INFARCTION  cells die and become BLACK AND SHRIVELED eschar

42. A heart attack or myocardial infarction results in irreversible cell damage.  True  False

43. The picture below is an example of:  Wet gangrene  Dry gangrene  Gas gangrene

44. Gangrene Gangrene is necrosis of a mass of tissue Gangrene is necrosis of a mass of tissue  Death of many cells!  Death of many cells! Results from severe hypoxia and subsequent ischemia Results from severe hypoxia and subsequent ischemia Often seen with impaired circulation to lower extremities (PVD, Diabetes) Often seen with impaired circulation to lower extremities (PVD, Diabetes) Three types of gangrene: Three types of gangrene: 1) Dry gangrene 2) Wet gangrene 3) Gas gangrene

45. Dry Gangrene  Part of the tissue becomes dry and shrinks, the skin wrinkles and color changes to brown or black  Shriveled/mummified  Spread is slow  Results from chronic ischemia of tissue  Symptoms not as marked as with wet gangrene

46. Dry Gangrene  Line of inflammatory reaction occurs between dead tissue and health tissue  Usually d/t interference IN ARTERIAL supply to a part without interfering with venous return so no swelling  No bacterial infection  Mostly confined to extremities Note the clear line of demarcation

47. Moist or wet gangrene  Frequently occurs in internal organs (appendix)  If on the skin, surrounding area is cold, swollen, and pulseless  Skin in moist, black, and under tension  Blebs form on the skin, liquefaction occurs, and foul odor develops from bacteria  No line of demarcation  Spread is rapid

48. Moist or wet gangrene Severe systemic symptoms may develop Changes in VS, LOC, kidney function Death may occur Venous return is impaired so see swelling Bacterial invasion is present May affect extremities or internal organs Dry gangrene may become wet gangrene if a bacterial invasion occurs

49. membranes) Gas Gangrene *(destroys connective tissue and cellular membranes) Is a specialized type of wet gangrene Results from infection of devitalized with clostridium bacteria Anaerobic and spore forming, clostridium are often found in the soil Gas gangrene is more prone to occur when there is trauma with a compound fracture

50. Gas gangrene Bacteria produce toxins which dissolve cell membranes causing: death of muscle cells massive spreading edema hemolysis of RBCs renal toxicity Characteristic bubbles of hydrogen (sulfide gas) form in the muscle Can be fatal Note characteristic gas bubbles