Pathology 2 Flashcards
What are the forms of repair?
Regeneration and scarring
What’s regeneration?
Repair with the growth of fully functional tissue to replace injured or dead tissue
What is required for total pure regeneration?
An intact connective tissue scaffold or only superficial injury (so it’s rare)
What’s a superficial injury?
Only affects epidermal or epithelial layer
Scarring replaces injured/dead tissue with ______.
Fibrous tissue lacking the specialized function of the tissue it replaces
What’s the most common scenario of wound repair?
A regeneration/scarring combo
Removal of one kidney causes _______. Is this regeneration?
Hyperplasia and hypertrophy of the remaining kidney, which doubles in size. Nope, not regeneration.
Removal of one lobe of the liver causes ______. Is this regeneration?
Hyperplasia and hypertrophy of the remaining lobe, which generate the same volume of fully functional liver tissue as pre-removal. Yep, regeneration.
What’s an ulcer?
A local defect in the surface of an organ or tissue produced by shedding of inflamed necrotic tissue
What’s an erosion?
Superficial sloughing of mucosa (or epidermis)
T or F: Ulcers are too deep to heal by regeneration.
T
What’s an adhesion?
An abnormal connection between any two things in the body
Early on, adhesions are composed primarily of _____. What is this called?
Fibrin, fibrinous
Later on, adhesions are referred to as _____.
Fibrous
What’s a fistula?
An abnormal opening between two places in the body
T or F: Fibrous adhesions are an inevitable side-effect of surgery.
T
What’s a common complication of fibrous adhesions?
Intestinal obstruction
_________ cells have self-renewal capacity.
Stem
Stem cells undergo ____ replication.
Asymmetric: in every division, one daughter cell retains self-renewing capacity and the other enters a differentiation pathway to a mature cell.
What are pluripotent stem cells?
They can give rise to any tissue
T or F: Adult stem cells can give rise to any tissue.
F: Limited number of tissues
What is the replicative capacity of labile cells?
They continuously lose cells and replace them by proliferation of mature cells and stem cells
What are examples of labile tissues?
Skin and linings of the mouth GI tract Bladder Vagina Cervix Uterus Fallopian tubes Exocrine gland ducts Bone marrow
What is the replicative capacity of stable cells?
They’re composed of cells capable of proliferation, but they’re not normally called on to proliferate
What are examples of stable tissues?
Liver Kidney Pancreas Smooth muscle tissues Blood vessel linings Fibroblasts
What is the replicative capacity of permanent cells?
They don’t proliferate except under extraordinary circumstances
What are examples of permanent tissues?
Parenchymal cells of the brain and heart (neurons and cardiac myocytes)
Which tissues are particularly vulnerable to radiation injury?
Continuously proliferating labile tissues
Erythema
Redness
Pruritis
Itching
Desquamation
Sloughing
Side effects of radiation
- Skin: erythema, pruritis, desquamation, loss of hair
- Chest/Abdomen: vomiting, nausea, diarrhea
- Bone marrow: Leukopenia
The process of healing is orchestrated by _____.
Growth factors
What does EGF stimulate?
Fibroblast migration and proliferation
What does FGF stimulate?
Fibroblast migration and proliferation
Monocyte chemotaxis
Angiogenesis
What does PDGF stimulate?
Fibroblast migration and proliferation
Monocyte chemotaxis
(more prevalent early in the process)
What does TGF-beta stimulate?
Fibroblast migration and proliferation
Monocyte chemotaxis
Collagen synthesis
T or F: TGF-beta is more prevalent early in the repair process.
F: more prevalent later in the process
What growth factors mediate monocyte chemotaxis?
PDGF, FGF, TGF-beta
What growth factors mediate fibroblast migration and proliferation?
PDGF, EGF, FGF, TGF-beta
What growth factors mediate angiogenesis?
FGF and VEGF
What growth factors mediate collagen synthesis?
PDGF and TGF-beta
What comprises the extracellular matrix?
Basement membrane and interstitium
Where is the basement membrane of the ECM?
Right underneath the epithelium and around blood vessels
What’s the interstitium of the ECM?
Supporting tissue between epithelium and vessels and between cells in connective tissue
What does the interstitium of the ECM contain?
Fibrillar collagen, fibrillin, elastin, hyaluronic acid, and proteoglycans
Which types of collagen are fibrillar?
I, II, III, and V
Review time! What’s the general structure of collagen?
3 polypeptide chains braided into a ropelike triple helix
What strengthens fibrillar collagen?
Lateral cross links
What are characteristics of the classical form of Ehlers-Danlos syndrome?
- A disease that causes defective type V collagen, leading to hypermobile joints and hyperextensible skin
- Autosomal dominant
What are characteristics of the vascular type of Ehlers-Danlos syndrome?
- It causes defective type III collagen, which is prevalent in blood vessels and bowel wall
- Autosomal dominant
What are characteristics of the kyphoscoliotic type of Ehlers-Danlos syndrome?
- It’s due to deficiency of lysyl hydroxyls enzyme, which impairs the cross linking of type I and III collagen
- Results in crooked spines
- Autosomal recessive
Fibrillin is secreted by ______ and is a major component of _____.
Fibroblasts, microfibrils
Microfibrils serve as scaffolding for the deposition of ________, an integral component of elastin.
Tropoelastin
What are the characteristics of Marfan syndrome? :(
- Caused by defects in the fibrillin gene
- Long body, long limbs, fingers, and toes
- Aorta prone to rupture
Loss of microfibrils leads to _____.
Excessive TGF-Beta
What is being evaluated as treatment for Marfans?
ARBs (angiotensin receptor blockers) that inhibit the activity of TGF-Beta, which is in excess in Marfan syndrome
What enzymes catalyze the formation of the covalent bonds cross-linking fibrillar collagen? What cofactor is needed?
Prolyl hydroxylase and lysyl hydroxylase; Vitamin C
What happens in vitamin C deficiency?
It weakens blood vessels, resulting in bleeding and poor wound healing
What pattern of inheritance do genetic defects in structural proteins tend to have?
Autosomal dominant
What pattern of inheritance do genetic defects in enzymes tend to have?
Autosomal recessive
What’s granulation tissue?
Healing tissue with residual chronic inflammatory cells, cellular debris, fibroblasts, neovascularization, and new collagen
What does granulation tissue look like?
Red or pink, soft, and granular
What are the number 1 and 2 features that are most characteristic of granulation tissue?
- Angiogenesis
2. Proliferating activated fibroblasts
What makes granulation tissue soft?
The new blood vessels of early granulation are leaky and the fluid that leaks out of them makes granulation tissue soft
What makes granulation tissue hard?
Replacement of granulation tissue by scar
What is organization?
The process replacing injured, necrotic, and inflamed tissue by healing and scar tissue
Who’s the key player in the process of organization?
Fibroblast
What’s the order of cell appearance in skin wound inflammation and healing?
- Neutrophils
- Macrophages
- Fibroblasts
- Lymphocytes
What’s the order of cell appearance in MI inflammation and healing?
- Neutrophils
- Lymphocytes
- Macrophages
- Fibroblasts
What do macrophages do in skin wounds?
Come early, peak fast, and leave fast
What do macrophages do in MI?
Come late, peak slowly, and persist for weeks
What’s angiogenesis?
The formation of new blood vessels in healing tissue, tumors, and atherosclerosis
What mediates angiogenesis?
VEGF (which also increases vascular permeability, endothelial migration, and proliferation)
How does angiogenesis work in skin wounds?
Starts early, peaks soon, and dissipates fast
How does angiogenesis work in MI?
Begins simultaneously with fibroblast infiltration on day 4, and persists for weeks
What are the phases of skin wound healing?
Inflammation
Proliferation
Maturation
When does healing by first intention occur?
When wounds are clean, uninfected, and have their edges approximated by sutures
When does healing by second intention occur?
In larger wounds with commonly irregular edges
In healing by first intention, on what day do all the playas come in?
1: Neutrophils
2: Epithelial cells
3: Macrophages
4: Fibroblasts
5: Granulation, angiogenesis
7-14: Collagen
What happens in healing by second intention?
- A larger blood clot fills the space of the wound
- More intense inflammation and more granulation tissue
- Wound contraction by myofibroblasts
- Scar formation
- Tissue remodeling
- Thinning of epidermal layer
The third phase of healing is a matter of ______.
Tissue remodeling, which alters the cellular content and extracellular matrix
What is the “high point” of healing?
The proliferative phase (middle phase)
What are the most characteristic features of the proliferative phase?
- Angiogenesis
2. Fibroblast proliferation
What is the most important growth factor driving angiogenesis?
VEGF
What do VEGF growth factors do?
Stimulate migration and proliferation of endothelial cells at the site of injured blood vessels, which sprout new blood vessels
When is neovascularization harmful?
In some retinal diseases such as wet diabetic retinopathy, macular degeneration, and retinopathy of prematurity
How do you treat retinal diseases where neovascularization is harmful?
By injecting antibody to VEGF into the eye
What is the most important growth factor driving fibroblast migration, proliferation, and collagen synthesis?
TGF-beta
Remodeling of ECM requires ________.
Breaking down collagen and other matrix components
What enzymes assist in the break down of collagen and other ECM components? (5)
Matrix metalloproteinases (MMP-1, 2, etc) Cathepsin G Plasmin Neutrophil elastase Serine proteinases
Matrix metalloproteinases depend on ____ for their action.
zinc
How are MMPs controlled?
By TIMPS (tissue inhibitors of metalloproteinases) and by tight control of their synthesis and secretion
How does location of a wound affect its healing?
Relative blood supply determines how well a wound heals
What can impair wound healing?(11)
- Infection
- Age
- Diabetes
- Anemia
- Corticosteroids
- Mechanical stress
- Poor perfusion
- Foreign material
- Obesity
- Chemo/radiation
- Fibroblast aberrancy
What is the most important cause of impaired wound healing?
Infection
How can corticosteroids delay wound healing?
By inhibiting protein and collagen synthesis
How can diabetes mellitus impair wound healing?
Primarily because of microangiopathy (small blood vessel disease) associated with it, but it also pours excess sugar into the wound (nutrients for infecting organisms)
How can anemia delay wound healing?
It decreases oxygen delivered to the site of repair
Why was grandma right about not picking your scabs?
It can disrupt the underlying partial epidermal layer and granulation tissue, setting back the healing process
What’s dehiscence?
Rupture of a surgical wound or anastomosis
What’s a hernia?
Protrusion of a body part somewhere it doesn’t belong
Keloid
Hypertrophic scar
Contracture
Abnormal excess wound contraction resulting in deformity and impaired movement
Where is contracture most common and what disease is associated with it?
Palms (Dupuytren’s contracture)
Soles (Lederhosen disease)
Penis (Peyronie disease)
What’s fibrosis?
Excessive interstitial collagen deposition usually due to chronic inflammation, recurring injury, persistent toxin, radiation, or autoimmune attack
What causes the WORST fibrosis? And why?
Autoimmune diseases because the inciting agent is continually present and can’t be limited or eliminated
What’s scleroderma?
It shows how bad fibrosis can be! Progressive fibrosis of the fingers until they’re fixed into a claw hand, sometimes with gangrene of the fingertips. The face undergoes fibrosis until its frozen into an “iron mask”. It kills peristalsis to move food into the stomach. It also leads to renal failure. Basically your life is the worst.
Who made the link of disease to malfunction at the cellular level?
Virchow
What are common causes of cell injury? (7)
- Oxygen deprivation
- Physical agents/trauma
- Chemical agents and drugs
- Infectious agents
- Immunologic reactions
- Genetic derangements
- Nutritional imbalances
T or F: All cells have potential for exhibiting both reversible and irreversible cell injury.
T
If an injurious stimulus is such that a cell can recover, you’ll see ______.
Reduction in biochemical and physiological function
T or F: You’ll see gross pathologic changes due to cell injury first.
Nope, you’ll see those last
Atrophy
Decrease in the size and function of a cell or organ
Common causes of atrophy (6)
- Disuse
- Loss of innervation
- Diminished blood supply
- Inadequate nutrition
- Loss of endocrine stimulation
- Aging
What are gyri vs. sulci?
Gyri: brain substance
Sulci: spaces between the substance of the brain
If you have brain atrophy, what happens to the sulci?
They get bigger
Hypertrophy
Increase in size of a cell caused by an augmented functional demand or specific hormonal stimulation
Growth in the size of uterine muscle fibers during pregnancy is an example of _______.
Physiologic hypertrophy
Increased thickness of the left ventricular wall of the heart in systemic hypertension is an example of ______.
Pathologic hypertrophy
Hyperplasia
Increase in the number of cells in an organ or tissue
Increased number of lactational units in the breast during pregnancy is an example of ______.
Physiologic hyperplasia
What’s an example of pathologic hyperplasia?
Benign prostatic hyperplasia
Malignancy of epithelial tissue is known as ______.
Carcinoma
Polyploidy
The state of a cell nucleus containing three or more haploid chromosomal sets
T or F: Polyploidy may occur naturally or as cellular adaptation.
T
T or F: Polyploidy is an indicator of unrestricted cell growth.
It’s an indicator but it doesn’t always indicate unrestricted cell growth
Metaplasia
Conversion of one differentiated cell type to another differentiated cell type
T or F: Metaplasia is irreversible.
F
What are the types of metaplasia?
Epithelial metaplasia and mesenchymal metaplasia
Epithelial metaplasia commonly occurs as a precursor to ______.
Dysplasia/neoplasia
T or F: Mesenchymal metaplasia is commonly preneoplastic.
F: rarely if ever
What effects can smoking have on respiratory epithelium?
Can change pseudoolumnar ciliated epithelium to squamous epithelium
What effects can HPV have on cervical epithelium?
Can change columnar to squamous
Dysplasia
Alteration of size, shape, and organization of the cellular components of a tissue
What are the characteristics of dysplasia?
- abnormal size and shape of cells
- enlargement, irregularity, and hyperchromasia of the nuclei
- disorderly arrangement of cells within the epithelium
- generally a preneoplastic condition
T or F: Dysplasia is almost always preneoplastic.
T
Which pigments are brown?
- Iron compounds
- Lipofuschin
- Melanin
What entities are responsible physiologically for iron stores?
Ferritin and hemosiderin
What is the principal storage form of iron?
Ferritin
What does hemosiderin consist of?
Intracellular granules in iron-storing cells
What is hemochromatosis?
A hereditary disorder in which too much iron is absorbed or retained
What is hemosiderosis?
Iron overload due to systemic or local causes
Hemosiderin is visible by _____.
Routine microscopy
Hemochromatosis is an (exogenous/endogenous) disease of iron storage, and hemosiderosis is (exogenous/endogenous).
Hemochromatosis: endogenous
Hemosiderosis: exogenous
What stain can be applied to brown iron pigment to make it blue?
Prussian blue stain
What’s lipofuschin?
- “Wear and tear pigment”
- A brown pigment of aging
- A polymer of oxidized lipids which are present in long-lived cells
What’s melanin?
- Brown pigment normally present in the basal layer of skin, retina, and some other ectodermal derived tissues
- Absorbs harmful UV light
Black pigments encountered in pathology most often include ______.
Carbon
What is anthracosis?
Black pigment grossly and microscopically in the lungs, pulmonary lymph nodes, and in distant tissues
-Permanent but harmless as long as surrounding tissues don’t react to the carbon
What happens when silica is inhaled at the same time as carbon?
Bad things happen
What benefit does proper calcification provide?
Maintains our skeletal framework
What is dystrophic calcification?
- Generally localized process, related to some tissue injury
- Plasma calcium levels are normal
What is metastatic calcification?
- Generalized process, may be calcification of many tissues
- Calcium levels may be elevated
- May be disarrangement of the balance between calcium and phosphate
Which is more common: dystrophic or metastatic calcification?
Dystrophic
Calcium salts using _________ and _______ stain are purple.
Hematoxylin and eosin
When does dystrophic calcification have a positive clinical use?
In mammograms
Why might water and electrolytes leak into cells?
Due to vacuole formation or to hydropic swelling
T or F: Hydropic swelling is an early indicator of cell damage.
T
Which lipids may accumulate in cells under abnormal conditions?
Triglycerides and cholesterol
What is xanthelasma?
Soft, yellow, orange-like plaques on the eyelids or on the medial canthus; they represent abnormal lipid deposition
How are triglycerides seen grossly?
As yellow, greasy deposits in diseased organs whose cells are engorged with triglyceride droplets and vacuoles (Steatosis)
Where is steatosis most common?
Liver (most common!), but also in heart, skeletal muscle, and kidney cortex
What is kwashiorkor?
- A disease related to a low protein/high carb diet
- Results from the lack of protein synthesis and retention of lipid components
Abnormal deposition of cholesterol can lead to _______.
Can lead to severe disease or may only be a histologic curiosity
________ may increase intracellularly in conditions such as diabetes or hypoxia.
Glycogen
Where might you see a Laffora body?
In some severe CNS diseases
Where might you see corpora amylaceae?
Typically extracellular; may be seen in the meninges, ventricles, and in the ependyma
-generally of no significance
What is Mallory’s alcoholic hyalin?
Condensed cytoskeletal protein seen in the cytoplasm of patients who have been exposed to alcohol in extreme amounts over long periods of time
Homeothermic
Capable of maintaining body temperature within very narrow limits
What temperature reflects the temperature of the core of the body most accurately?
The esophagus at the cardia
Normal body temperature can vary due to ___________.
Exogenous or endogenous factors
What are examples of exogenous factors that can change the normal core temperature?
Climatological environment Peripheral insulation Diet Physical activity Drugs
What are examples of endogenous factors that can change the normal core temperature?
Rhythms (i.e. circadian rhythm) Gender Age and body size Subcutaneous insulation Water content Physiological state
Most energy is lost as ____.
Heat
Total energy expenditure =
Internal heat produced + external work performed + energy stored
Radiation
Heat transmitted via electromagnetic waves
Conduction
Heat transfer within a solid or between two or more solids in close contact
Convection
Heat transfer in a fluid or between a fluid and a solid
Evaporation
Heat transfer by means of a change in state, from a liquid to a gas.
What factor affects evaporation?
Humidity – dry air increases evaporation, humid air decreases evaporation
What is the zone of thermal neutrality?
The range of ambient temperature in which the body maintains its heat balance without increasing heat production or loss above their minimum level
T or F: Higher the ratio SA/V, higher the heat loss.
T duhh
What serves as the primary overall integrator of reflexes and the brain’s inner thermostat?
Hypothalamus
Where are warm fibers located?
In Ruffini’s corpsucles
Where are cold fibers located?
In the end-bulb of Krause
What effect does epinephrine have on metabolic activity?
It increases metabolic activity
(Vasodilation/Vasoconstriction) leads to reduced heat loss.
Vasoconstriction
Neonatal ______ may occur if brown fat is lacking.
Hypothermia
How does thyroid hormone affect metabolic rate and heat production?
TH acts on the sodium/potassium pump and increases O2 consumption. This increases metabolic rate and heat production.
(Hot/Cold) temperatures activate thyroid hormone.
Cold
What is the relationship between hyperthyroidism and temperature control?
Metabolic rate is increased so heat production increases
What is the relationship between hypothyroidism and temperature control?
Metabolic rate decreases and there is decreased heat production (extreme sensitivity to cold)
What must happen for thyroid hormones to be maximally active?
The sympathetic nervous system must be simultaneously activated by cold temperatures
Sweating is accomplished through _______.
Specialized eccrine sweat glands found in the dermis and epidermis
Where don’t we have eccrine sweat glands?
Margins of the limbs, sex organs, and ear drums
Sweat glands consist of __________.
A deep coiled portion and a duct that opens on the skin
The duct of the sweat gland aids in ________.
Resorption of electrolytes (mainly Na and Cl) in the sweat so that the fluid discharged onto the skin has a reduced electrolyte concentration
Why do we shiver?
It results from somatic activation of skeletal muscles which asynchronously contract.
How can you suppress shivering?
It’s normally involuntary, but it can be suppressed by higher cortical input (a learned process)
What are differences in body temperature in men and women?
- Core body temperature cools more slowly in women
- Women can’t create as much metabolic heat through exercise or shivering
- The rate of cooling of the extremities is faster among women
What does the body do during heat exhaustion?
- Vasodilation
- Excess sweating –> decreases ECF volume –> decreased blood volume –> decreased arterial pressure –> fainting
What does the body do in heat stroke?
The body temperature increases to a point of tissue damage
What is malignant hyperthermia?
A usually hereditary condition where there is a massive increase in metabolic rate
What are the differences between fever and hyperthermia?
- Fever is regulated, hyperthermia is an impairment
- Fever is independent of ambient temperature, and hyperthermia is dependent on ambient temperature
- Fever has increased thermopreferendum, and hyperthermia has decreased thermopreferendum
What are some microbial stimuli that can induce fever?
Viruses, bacteria, mycobacteria, and fungi
What are some non-microbial pathogenic stimuli that can induce fever?
Antigens, inflammatory agents, plant lectins, or host-derived stimuli
What are the benefits of fever?
- enhanced neutrophil migration and T-cell proliferation
- enhanced phagocytosis
- increased IFN production/activity
- increased radical production
- reduced growth rate and viability of iron-dependent microorganisms
- increased survival rate
What are some hazardous effects of high or prolonged fever?
- dehydration
- delirium
- cardiopulmonary strain
- negative nutrient balance
- teratological consequences
