Concepts in Pathology and Cellular Injury Flashcards Preview

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1
Q

Pathology

A

The study of the essential nature and characteristics of disease, including signs/symptoms, complications, pathogenesis, and morphologic consequences including structural and functional alterations in cells, tissues, and organs

2
Q

Disease

A

An impairment of the normal state of the living animal or plant body or one of its parts that interrupts or modifies the performance of the vital functions, is typically manifested by distinguishing signs and symptoms, and is a response to environmental factors (as malnutrition, industrial hazards, or climate), to specific infective agents (as worms, bacteria, or viruses), to inherent defects of the organism (as genetic anomalies), or to combinations of these factors

3
Q

Homeostasis

A

the tendency toward a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes.

4
Q

Morbidity

A

a diseased state or symptom; the incidence of disease : the rate of sickness

5
Q

Comorbidity

A

the simultaneous presence of two chronic diseases or conditions in a patient.

6
Q

Mortality

A

the state of being subject to death.

7
Q

Iatrogenic

A

of or relating to illness caused by medical examination or treatment.

8
Q

Idiopathic

A

relating to or denoting any disease or condition that arises spontaneously or for which the cause is unknown.

9
Q

Signs and Symptoms

A

signs: any indication of a medical condition that can be objectively observed
symptom: any manifestation of a condition that is apparent to the patient

10
Q

Self-limiting Disease

A

a disease process that resolves spontaneously with or without specific treatment.

11
Q

death

A

the action or fact of dying or being killed; the end of the life of a person or organism.

12
Q

Illness

A

an unhealthy condition of body or mind – (sickness or disease)

13
Q

Syndrome

A

a group of signs and symptoms that occur together and characterize a particular abnormality or condition

14
Q

Etiology

A

Cause
• Genetic
• Acquired

15
Q

Pathogenesis

A

• Temporal sequence and patterns of cellular injury that lead to disease

16
Q

Morphology

A
  • Gross changes

* Microscopic changes

17
Q

Clinical Significance

A
  • S+S specific for the disease
  • Disease course (complications)
  • Prognosis
18
Q

What are the gold standards for microscopic tissue examination?

A

Hematoxylin and Eosin (H&E) is the gold standard
• Eosin stains the cytoplasm, RBC’s and collagen pink to red
• Hematoxylin stains nuclei and bacteria (and some other structures) blue to purple

19
Q

Other stains used for tissue examination?

A
  • Prussian blue – Iron
  • Congo red – amyloid
  • Gram stain – bacteria
  • Trichrome - cells and CT
20
Q

Molecular Techniques

A
  • Protein electrophoresis
  • Southern blot
  • Northern blot
  • Western blot
  • Dot blot
  • PCR
21
Q

Hypoxia

A

Most common cause of cellular injury
• Lack of oxygen results in the inability of the cell to synthesize sufficient ATP by aerobic oxidation
• Ischemia - Most common cause
• Cardiopulmonary failure
• Decreased oxygen carrying capacity (anemia CO)

22
Q

How do Infections cause cellular injury?

A
Viruses, bacteria, parasites, fungi, and prions
Causes injury by:
• Direct infection
• Toxins
• Host inflammatory response
23
Q

Immunologic reactions

A
  • Hypersensitivity reactions

* Autoimmune disease

24
Q

What are the major causes of cellular injuries?

A
Hypoxia
Infections
Immunological Reactions
Congenital Disorders
Chemical Injuries
25
Q

Congenital Disorders

A

Inborn errors of metabolism and genetic disorders

26
Q

Chemical Injuries

A
  • Drugs
  • Poisons
  • Pollution (Smog)
  • Occupational exposure
27
Q

Cloudy Swelling

A

If continued, this leads to irreversible damage. Intracellular proteins accumulate in the serum with cellular degeneration.

28
Q

Physical forms of injury

A
  • Trauma
  • Burns
  • Frostbite
  • Radiation
  • Pressure changes
29
Q

Nutritional or vitamin imbalance

A

• Marasmus: decrease in total caloric intake
• Kwashiorkor: decrease in total protein intake
• Anorexia
- Excessive Caloric Intake: obesity; atherosclerosis

30
Q

• Vitamin A

A

squamous metaplasia, immune deficiency, night blindness

31
Q

Vitamin C

A

Scurvy

32
Q

Vitamin D

A

Rickets & Osteomalacia

33
Q

Vitamin K

A

Bleeding Diathesis

34
Q

Vitamin B 12

A

Megaloblastic anemia, neuropathy, spinal cord degeneration

35
Q

Folate

A

Megaloblastic anemia and Neural Tube Defects (NTD)

36
Q

Niacin

A

Pellagra (diarrhea, dermatitis, and dementia)

37
Q

Cellular Responses to Injury

A
  • Adaptation
  • Reversible injury
  • Irreversible injury and cell death (necrosis/apoptosis)
38
Q

Cloudy Swelling And Hydropic Degeneration

A
  • Cellular swelling appears whenever cells are incapable of maintaining ionic and fluid homeostasis
  • Decreased ATP concentration and decreased Na pump activity causes Na and water to accumulate intracellularly (Calcium also rises).
  • The result is an isosmotic gain of water.
39
Q

Cellular Response Depends Upon:

A
  • Type of injury
  • Duration, and pattern of injury • Severity and intensity of injury • Type of cell
  • Cells metabolic state
  • The cells ability to adapt
40
Q

Critical Intracellular Systems that are Susceptible to Injury are:

A
  • DNA
  • Production of ATP via aerobic respirations
  • Cell membranes Protein synthesis
41
Q

What causes injury to critical inracellular systems?

A

Damage to DNA, lipid membranes, proteins, and circulating lipids (LDL) caused by oxygen- derived free radicals

42
Q

Important Mechanisms of Cell Injury

A
  • Mitochondrial Dysfunction
    • Decrease in oxidative phosphorylation –> ATP –> mitochondria highly permeable
    • Release of cytochrome c is a trigger for apoptosis
    • The Na+K+ATPase pumps start to fail
    • Influx of Na and H20; Efflux of K
    • Cellular swelling
    • Swelling of the ER
43
Q

ATP depletion

A

Increased cell membrane permeability –> Influx of calcium
• Second messenger
• Activates a wide spectrum of enzymes
• Proteases–> protein breakdown
• ATPase –> contributes to ATP depletion
• Phospholipases –> cell membrane injury
• Endonucleases –> DNA damage

44
Q

Severe membrane damage

A
  • Marked mitochondrial dysfunction leading to swelling and decreased ATP
  • Rupture of lysosomes
  • Nuclear changes
  • Pyknosis (degeneration and condensation of nuclear chromatin
  • Karyorrhexis (nuclear fragmentation)
  • Karyolysis (dissolution of the nucleus
45
Q

Morphologic Types of Necrosis

A
Coagulative Necrosis
Liquefaction Necrosis
Caseous Necrosis
Fat Necrosis
Fibrinoid Necrosis
Gangrenous Necrosis
46
Q

Coagulative Necrosis

A
  • Most common form of necrosis
  • Denaturing and coagulation of proteins in cytoplasm (mosquito reminder)
  • Common in most organs like liver, heart kidney
47
Q

Liquefaction Necrosis

A
  • Cell destruction by hydrolytic enzymes
  • Due to autolysis (release of proteolytic enzymes)
  • Found in abscesses, brain infarcts and pancreatic necrosis
48
Q

Caseous Necrosis

A
  • Combination of coagulation and liquefaction necrosis
  • Gross: soft, friable “cottage cheese- like” appearance
  • Characteristic of granulomatous diseases like TB
49
Q

Fat Necrosis

A
  • Caused by lipases acting on adipocytes

* Fat necrosis has a chalky white appearance

50
Q

Fibrinoid Necrosis

A
  • Necrotic CT that resembles fibrin
  • Has an eosinophilic (pink) pattern
  • Often from acute immunologic injury (hypersensitivity type reaction)
51
Q

Gangrenous Necrosis

A
  • General term for dead tissue
  • Common in the LE, GB, GI tract
  • Dry gangrene micro appearance is Coagulative necrosis
  • Wet gangrene micro appearance is liquefactive necrosis
  • Gas – specific to Clostridium perfringens
52
Q

Apoptosis

A

Specialized form of cell death without an inflammatory response; Suicide Programmed Cell Death
• Regulated by genes
• Usually only affects only single
cells or small groups of cells
• Morphologic appearance:
o Cell shrinks and has dense eosinophilic cytoplasm
o Chromatin condensation then fragmentation
o Formation of membrane blebs o Breakdown of the cell into fragments (apoptotic bodies)
o Phagocytosis of apoptotic bodies by macrophages
• NO INFLAMMATORY RESPONSE

53
Q

What is the stimulus for apoptosis?

A
  • Cell injury and DNA damage
  • Lack of growth factors or needed hormones
  • Receptor-ligand signals
  • Fas binding to the Fas ligand
  • Tumor necrosis factor TNF binding to TNF receptor 1 (TNFR1)
54
Q

Tumor necrosis factor TNF binding to TNF receptor 1 (TNFR1)

A
  • an orderly progression without inflammation
  • changes in adhesion
  • cell membrane divides into apoptotic bodies
  • essential for involution of tissues
  • essential for cancer cures
55
Q

Which genes regulate Apoptosis?

A

bcl-2 (inhibits apoptosis)
- Prevents release of cytochrome c from mitochondria
- Binds pro-apoptotic protease activating factor (Apaf-1)
p-53 (stimulates apoptosis)
- Elevated by DNA injury and arrests the cell cycle
- If DNA repair is impossible, p53 stimulates apoptosis

56
Q

How is the execution of apoptosis mediated?

A
  • Mediated by a cascade of caspases
  • Caspases digest nuclear and cytoskeletal proteins
  • Caspases also activate endonucleases
57
Q

Host susceptibility factors

A
  • Emotional states: Unresolved states, Cognitive dissonance, Sympathetic dominance, Dysfunctional breathing patterns, Perfectionism, Secondary gain, Negative self-talk
  • Air
  • Water
  • Rest
  • Sleep (REM sleep)
  • Activity (Walking and gait)
58
Q

Atrophy

A
• Decrease in cell or organ size and functional ability
Causes include:
• Decreased workload or disuse (immobilization)
• Ischemia (atherosclerosis)
• Lack of hormonal or neural
stimulation
• Malnutrition
• Aging
59
Q

Hypertrophy
What are the causes?
What is it mediated by?

A

Increase in cell size and functional ability due to increased synthesis of intracellular components
Causes include:
- Increase Mechanical Demand
• Physiologic: striated muscle or weight lifters
• Pathologic: cardiac muscle in hypertension
• Increased endocrine stimulation
• Puberty (GH, androgens/estrogens)
• Gravid Uterus (estrogen)
• Lactating breast (prolactin & estrogen)
Hypertrophy is mediated by:
• Growth factors, cytokines, and other trophic stimuli
• Increased expression of genes and increased protein synthesis
Hypertrophy and hyperplasia often occur together

60
Q

Hyperplasia

A

Increase in the number of cells in a tissue or organ
Some cell types are unable to exhibit hyperplasia (e.g., nerve, cardiac, skeletal mm cells
• Physiologic causes of hyperplasia:
• Compensatory (after partial hepatectomy)
• Hormonal stimulation (breast development during puberty)
• Antigenicstimulation(lymphoidhyperplasia)
• Pathologic causes of hyperplasia • Endometrialhyperplasia
• Prostatic hyperplasia of aging
• Hyperplasia is mediated by:
• GF, cytokines and other trophic stimuli
• Increasedexpressionofgrowthpromoting genes (proto-oncogenes)
• IncreasedDNAsynthesisandcelldivision

61
Q

Metaplasia

A
  • Reversible change of one cell type to another, often in response to irritation
  • It’s suggested that the replacement cell is better able to tolerate the environmental stresses
  • i.e. bronchial epithelium undergoes squamous metaplasia in response to the chronic irritation of tobacco smoke
  • Proposed mechanism: the reserve cells (or stem cells)j of the irritated tissue differentiate into a more protective cell type due to the influence of growth factors, cytokines, and matrix components
62
Q

Dysplasia

A
  • An abnormal proliferation of cells that is characterized by changes in cell size, shape and the loss of cellular organization
  • Dysplasia is not yet cancer, buy may progress to cancer and this is considered to be a pre-neoplastic lesion
  • Examples: cervical dysplasia, actinic (solar) keratosis, and oral leukoplakia
63
Q

Types of Intracellular Accumulations

A

Lipids:
• Triglycerides (fatty change in liver cells)
• Cholesterol (atherosclerosis, xanthomas)
• Complex lipids (sphingolipid accumulation)
Glycogen storage diseases:
upcoming lectures

64
Q

Where does Fatty infiltration commonly occur?

A
  • pancreas
  • lymph nodes
  • right heart
  • muscle (CF
65
Q

Fatty Change or Steatosis

A
  • Abnormal accumulation of triglycerides. Seen in
  • liver
  • heart
  • muscle
  • kidneys
  • macrophages of the arterial intima in atherosclerosis.
  • Usually due to cellular metabolic damage and increased lipids
66
Q

Mechanism of Steatosis

A
• Too much free fat coming to the liver 
• Too much fatty acid synthesis
• Impaired fatty acid oxidation
• Excess esterification of fatty acids to triglycerides
• Too little apoprotein synthesis 
• Failure of lipoprotein secretion 
• Liver hypoxia
Morphology: A normal liver weighs 1500 gm – fatty infiltration may be as large as > 4000 gm
67
Q

Anthracosis –

A

Carbon Deposits

68
Q

Endogenous Pigment - Lipofuscin

A

• Wear and tear pigment
• Fine, granular often perinuclear yellow-
brown pigment
• Indigestible material within lysosomes
• Common in the liver and heart
• Composed of lipid, phospholipid and protein
• Aka lipochrome
• Derived from lipid peroxidation of subcellular membranes
• Not a pathological substance

69
Q

Endogenous Pigment - Hemosiderin

A
  • Hemoglobin derived
  • Golden yellow or brown
  • A major storage form of iron
  • Apoferritin + iron = ferritin
  • With local or systemic iron overload ferritin forms hemosiderin
70
Q

Local hemosiderosis: A bruise (ecchymosis)

A
  • Blood is phagocytosed by macrophages which recovers the iron
  • Heme is converted to biliverdin (green)
  • Biliverdin is converted to bilirubin (yellow)
  • Iron is incorporated into ferritin and eventually hemosiderin.
71
Q

Hyaline Degeneration

A
intracellular inclusions of any protein that stains pink with H&E stain
• ie. viral inclusions
• Deposits in alcoholic hepatocytes
• Keloid collagen
• Proximal tubule epithelial cells
• Amyloid* -(actually extracellular)
• Fibrinoid
72
Q

Calcification

A

• a process in which tissue or non-cellular material becomes hardened as the result of deposits of insoluble salts of calcium.
• structures that commonly calcify in adults:
pineal media of large arteries mitral valve annulus tracheal cartilages

73
Q

Metastatic Calcification

A
Occurs when there is elevated serum calcium or phosphate
when cancer destroys bone
milk abuse 
antacid abuse
parathyroid adenoma
74
Q

Dystrophic (Abnormal) Calcification

A
  • local calcification of non-viable tissues
  • Atheroma
  • TB
  • Psammoma bodies
  • Damaged heart valves
75
Q

Myxomatous Degeneration

A

definition – increased ground substance with damage to connective tissue fibers
• Cystic medial necrosis
• Mitral valve prolapse

76
Q

Amyloidosis

A
Idiopathic disease characterized by extracellular accumulation of amyloid in organs and tissues.
Amyloid is a pathologic protein found in a wide variety of clinical conditions
- B cell proliferations 
- Chronic inflammation 
- Chronic renal failure 
- Alzheimer disease 
- Type II diabetes
- Prion disease