Lectures 9 & 10 - Basis of Disease I & II Flashcards
1
Q
What is pathology?
A
Study of the structural and functional changes in cells, tissues, and organs of the body that cause or are caused by disease
2
Q
What is pathophysiology?
A
Not only cellular and organ changes that occur with disease, but also the effects that these changes have on total body function
3
Q
What 2 factors impact the cell’s response to stress?
A
- Duration of stress
2. Intensity of stress
4
Q
Are cellular adaptations to stress reversible?
A
YUP
5
Q
What are 5 cellular adaptations to stress?
A
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
- Dysplasia
6
Q
Describe atrophy.
A
Decrease in the size of a tissue resulting from a decrease in cell size or in the number of cells
7
Q
6 causes of atrophy?
A
- Disuse
- Loss of trophic stimuli
- Insufficient nutrients
- Decreased blood flow
- Persistent cell injury
- Aging
8
Q
Describe hypertrophy.
A
Increase in cell size, and thus an increase in the amount of functioning tissue mass
Involves an increase in the functional components of the cell that allow it to achieve equilibrium between demand and functional capacity
9
Q
Cause of hypertrophy?
A
Results from an increased workload imposed on an organ or body part
10
Q
Describe hyperplasia.
A
Increase in the number of cells in an organ or tissue and can only occur in tissues that are capable of mitotic division
Controlled process that occurs in response to an appropriate stimulus and ceases after the stimulus has been removed
11
Q
Physiologic hypertrophy examples?
A
- Exercise
2. Pregnancy: breasts, uterus
12
Q
Pathophysiogic hypertrophy example?
A
Kidney transplant: compensatory hypertrophy
13
Q
Describe metaplasia.
A
One adult cell type is replaced by another adult cell type
Thought to involve the reprogramming of undifferentiated stem cells that are present in tissue
14
Q
Cause of metaplasia?
A
Usually occurs in response to chronic irritation and inflammation which allows for substitution of cells that are better able to survive
15
Q
Describe dysplasia.
A
Characterized by deranged cell growth of a specific tissue that results in cells that vary in size, shape, and appearance
Involves sequential mutations in proliferating cell populations
Strongly implicated as a precursor of cancer
16
Q
Where is dysplasia most frequently encountered?
A
Metaplastic squamous epithelium of the respiratory tract and uterine cervix
17
Q
2 examples of pathophysiologic metaplasia?
A
- Trachea and bronchial tree ciliated columnar cells to stratified squamous cells in response to smoking
- Chronic GERD: epithelial cells of esophagus turn into gastric epithelial cells
18
Q
Why is dysplasia often thought of as irreversible (even though it is not)?
A
Because the stressors causing dysplasia are often very hard to remove (e.g. HPV)
19
Q
What does cell stress lead to?
A
- Adaptation
OR - Cell injury
20
Q
Can cell injury be reversible?
A
YUP, but not always
21
Q
7 causes of cell injury?
A
- Mechanical forces
- Electrical injuries
- Nutritional imbalances
- Biological agents
- Poisons and chemical agents
- Hypoxia
- Extremes of temperature
22
Q
How does heat affect cells?
A
- Accelerates cell metabolism
- Inactivates temperature sensitive enzymes
- Disrupts the cell membrane
- Coagulation of blood vessels
- Coagulation of tissue proteins
23
Q
How does cold affect cells?
A
- Increases blood viscosity
- Induces vasoconstriction (SNS)
- Ice crystal formation
- Capillary stasis
- Arteriolar and capillary thrombosis
24
Q
Is there a safe level of lead in the body?
A
NOPE
25
4 effects of high levels of lead in the body?
1. Mental retardation
2. Coma
3. Convulsions
4. Death
26
4 effects of low levels of lead in the body?
1. Reduced IQ and attention span
2. Impaired growth
3. Reading and learning disabilities
4. Hearing loss
27
Can lead cross the blood-brain barrier? Why/why not? What to note?
YUP because cannot tell the difference between lead and calcium
It also damages it
28
What other parts of the body does lead affect other than the CNS?
1. Causes an increase in ROS, and a decrease in antioxidant systems
2. Glomerular fibrosis and proximal tubule mitochondrial damage
29
How do agents causes cell injury?
1. Some agents (like heat) produce direct cell injury
2. Some agents (like genetic derangement) produce their effects indirectly through metabolic disturbances and altered immune responses
30
3 common causes of cell injury?
1. Depletion of ATP
2. Free radical formation
3. Disruption of intracellular calcium homeostasis
31
How does the depletion of ATP injure the cell?
1. Na+/K+ ATP-ase failure so the RMP is disturbed => membrane depolarization => increase in intracellular Ca++ and Na+ => cellular swelling => lysis
2. Switch to anaerobic metabolism => increase in lactic acid => decrease in cellular pH => lysing of lysosomes => lysosymes released => lysis
32
Is cellular swelling reversible?
YUP
33
What is the ischemic reperfusion cell injury?
Reperfusion of an ischemic tissue is more damaging than the ischemia itself
Ischemia => inflammation due to chemokines and ROS released by endothelial cells => reperfusion causing massive inflammatory response
34
On what organ are experiments studying ischemic reperfusion injuries done? Why?
Kidneys because the kidney only has one arterial blood supply to it's easy to cause ischemia
35
3 major effects of free radicals?
1. Lipid peroxidation on cellular membranes
2. Oxidative modification of proteins
3. DNA effects
36
What is a free radical?
Molecules with an unpaired electron
37
Other name for free radicals?
ROS
38
What is an anti-oxidant?
Molecule that can donate an electron to protect against free radicals
39
What causes the formation of free radicals? 6
1. Metabolism in mitochondria
2. Inflammation
3. Air pollution
4. Smoking
5. Ionizing radiation
6. UV light
40
Why does inflammation cause free radical formation?
WBCs are full of free radicals and when they phagocytose antigens they release these to help degrade them
41
What molecules do ROS target?
Large molecules
42
In what disease are ROS important?
Atherosclerosis
43
2 types of cell death? Describe each.
1. Apoptosis = programmed cell death that is rapidly cleared so it does not elicit an inflammatory response
2. Necrosis = disorganized cell death
44
4 steps of apoptosis?
1. Small blebs form
2. Nucleus begins to break apart, the DNA breaks into small pieces, and organelles are also located in the blebs
3. Cell breaks into several apoptotic bodies and the organelles are still functional
4. Apoptotic cells are phagocytosed by nearby immune cells which are signaled to approach
45
4 steps of necrosis?
1. Small blebs form and the structure of the nucleus changes
2. Blebs fuse and become larger and no organelles are located in them
3. Cell membrane ruptures and releases the cell's contents into the interstitial space and the organelles are not functional
4. Inflammatory response is triggered by cell contents and nearby cells are damaged
46
What is apoptosis propagated by?
A family of proteases called caspases
47
2 apoptotic pathways? Provide examples.
1. Intrinsic pathway: stress, viruses
| 2. Extrinsic pathway: tissue growth, embryological limb development, menstrual cycle
48
5 physiological reasons for apoptosis?
1. Removal of proliferating cell populations (intestinal epithelia)
2. Death of host cells that have served their useful purpose
3. Embryogenesis (webbing between the toes)
4. Control of immune cell numbers
5. Hormone-dependent involution of endometrial cells during the menstrual cycle
49
3 pathophysiological reasons for apoptosis?
1. Growth of cancers
2. Viral infections
3. Neurodegenerative disorders
50
What intracellular ion concentration increases with necrosis? What does this cause?
Ca++ => activates calpain => lysosome rupture => cathepsin release => cell death
51
Complication of necrosis?
Gangrene
52
2 types of gangrene? Describe each.
1. Dry gangrene: due to interference with arterial blood supply and starts in the extremities due to necrosis leading to bacterial infections => Hb breakdown into sulfate Hb => black color
2. Wet gangrene: due to interference with venous blood supply => same mechanism
53
In what patients is dry gangrene common?
Diabetics
54
Treatment for dry and wet gangrene?
Amputation
55
In what patients is wet gangrene common?
Bed ridden patients
56
What appears first when there is a liver issue: jaundice or bilirubin in urine?
Bilirubin in urine
57
What is HBsAG?
Hepatitis B surface antigen
58
What is hepatitis B?
DNA hepadnavirus
59
How is Hep B transmitted?
Transmitted by inoculation of infected blood or by sexual contact due to presence in saliva, semen, and vaginal secretions
60
5 groups at risk for Hep B?
1. Patients and staff at hemodiaylysis centers
2. Physicians
3. Dentists
4. Nurses
5. Personel working in clinical and pathology labs and blood banks
61
What do half of acute hep B patients have in common?
Half of all patients with acute hepatitis B have previously been incarcerated or treated for an STD
62
Hep B prevalence?
1.25 million people in US infected
400 million worldwide
63
What are the 2 major pathophysiology mechanisms of liver injury by the Hep B virus?
1. Direct cellular injury by the virus
| 2. Induction of the immune response
64
6 clinical signs of liver inflammation?
1. Fatigue
2. Hepatomegaly
3. Athralgias
4. Polyarteritis nodosa
5. Membranoproliferative glomerulonephritis
6. Jaundice
65
Describe what happens during HBV infection.
HBsAg is bound by hepatocyte surface receptors => immune tolerant phase during which the virus replicates without damaging the cell => viremia/immune response phase during which completed virions enter the circulation and infect other hepatocytes (ACUTE HEPATITIS) => virions taken up by APCs => APCs degrade virions and present them to lymphocytes => CD8 T cells become sensitized to HBV antigens present on infected hepatocyte cell surface =>
1. Non-specific inflammatory molecules released: TNF, ROS, proteases
2. Cytotoxic T cells destroy infected hepatocytes
=> AST/ALT, bilirubin, alkaline phosphatase levels increase
66
How long does the HBV immune tolerance phase last?
Up to 6 months or more
67
How often are RBCs recycled?
Every 120 days
68
What are RBCs broken down into? Pathway?
Broken down by the reticuloendothelial system into:
1. Globin (protein)
2. Heme => broken down by heme oxydase => biliverdin => bilirubin (from biliverdin with biliverdin reductase and NADPH) => carried to liver by albumin
69
3 possible immune outcomes of HBV infection?
1. HBsAg totally cleared = immune stage
2. Inactive carrier stage = no injury or inflammation of hepatocytes but patient can suffer from acute flares
3. If virus cannot be cleared and replication continues for >6 months = chronic hepatitis => continual destruction and regeneration of liver parenchyma
70
What is chronic hepatitis commonly due to?
Commonly due to poor T cell response in immunocompromised host due to HIV or in neonates
71
What does chronic hepatitis increase the risk of?
Cirrhosis and carcinoma
72
What is the risk if you have hep B + hep D?
Risk of chronic liver disease and fulminant hepatits
73
4 effects of liver failure?
1. Reduced liver protein synthesis
2. Impaired glycogenolysis and gluconeogenesis
3. Reduced production of bile salts
4. Impaired processing of endogenous steroid hormones
74
What 2 effects of HBV infection cause symptoms?
1. Non-specific inflammatory molecules released: TNF, ROS, proteases
2. Cytotoxic T cells destroy infected hepatocytes
75
What is the basis of many chronic diseases?
Chronic inflammation
76
Describe the inflammation pathway.
1. Infection, trauma, exposure to physical or chemical agents, tissue necrosis, foreign bodies, hypersensitivity reactions, endothelial injury
2. Immediate response of body's immune system = acute inflammation
3a. Vascular reaction = delivers plasma proteins and immune cells to the site of inflammation
3b. Cellular reaction = leukocyte extravasation and activation
77
Describe the vascular reaction in the inflammation pathway.
1. Histamine/NO release => vasodilation
2. Kinin system/Angiogenesis-related leakage/Endothelial contraction/leukocyte induced injury => increased vascular permeability
1 + 2 = 3. Increase in blood viscosity
4. Activation of complement proteins
5a. Increase vascular permeability
5b. Leukocyte adhesion, chemotaxis and activation
5c. Phagocytosis via opsonization
5 => further #2
78
Describe the cellular reaction in the inflammation pathway.
1. Endothelium activation
2. Leukocyte margination
3. Leukocyte rolling and pavementing
4. Leukocyte adhesion
5. Leukocyte emigration through endothelium
6. Leukocyte chemotaxis toward site of injury/infection
7. Leukocyte activation and phagocytosis
8a. Elimination
OR
8b. Tissue injury
79
4 examples of chemokines?
1. Bacterial products
2. Anaphylotoxins
3. Leukotrienes
4. Cytokines
80
Describe the chronic inflammation pathway.
1. Continuous activation of T cells
2. Accumulation and activation of macrophages
3a. Release of TNF-alpha
3b. Release of ROS and reactive nitrogen species => tissue damage => #6
4. Fibroblast proliferation
5. Tissue fibrosis
6. Altered structure and function of tissue
81
What is TNF-alpha?
A cytokine
82
Other than fibroblast proliferation, what are the other effects of TNF-alpha?
1. Increased cytokine release
2. Increased microbicidal activity
3. Tissue wasting
4. Increased expression of MHC II => increased inflammation and cell recruitment => inflammation exacerbation
83
Are males or females more affected by diabetic nephropathy? Why?
Males because stronger inflammatory response
84
What are athralgias?
Joint pain
85
What are polyarteritis nodusa?
Systemic vasculitis of small- or medium-sized muscular arteries
