Pathology week 1 Flashcards
Describe the adaptive changes cells and tissues undergo in pathological and physiological cases: hypertrophy
Hypertrophy: increase stress leads to an increase in size of cells results in increase of organ. Trying to work capability. May occur with hyperplasia = hypertropic organ. Can result in cellular injury if stress is not relieved.
Examples: pathologic: heart or physiologic (uterus)
Cell needs to get larger = cytoskeleton needs to grow = gene activation and protein synthesis; for a larger cell more organelles will need to be produced
Describe the adaptive changes cells and tissues undergo in pathological and physiological cases: hyperplasia
Uncontrolled hyperplasia can lead to what?
Hyperplasia: increase in cell number in response to stress. Important for wound healing - a balanced and controlled event. Uncontrolled can lead to neoplasia/cancer
Physio: hormonal, compensatory (pregnancy)
Patho: (eg endometrial hyperplasia) excess of hormones or growth factor can progress to dysplasia and eventually to cancer; another example prostatic hyperplasia (prostate)
Produced from stem cells
Exception: Benign prostatic hyperplasia (BPH) no increased risk of cancer
Example: uterus during pregnancy hyperplasia and hypertrophy occur together
- Exception: permanent cells undergo hypertrophy only (lack stem cells)
- permanent cells: cardiac myocytes, skeletal, nerve **
Describe the adaptive changes cells and tissues undergo in pathological and physiological cases: Atrophy
Atrophy: decrease in stress leads to decrease in cell size and/or number, decrease in function (cells survive). Mech: decrease workload, innervation, blood supply, endocrine, stimulation, nutrition, pressure
Mech: decreased protein synth, increased degradation in cells, autophagy “self eating” (vacuoles fuse with lysosomes
* Decrease in number of cells occurs via apoptosis
*Decrease in size: ( 1) ubiquitin-proteosome degradation of the cytoskeleton (intermediate filaments get tagged and then destroyed by the ubiquitin proteosome; ( 2) autophagy of cellular components fuse with lysosomes and get consumed
Describe the adaptive changes cells and tissues undergo in pathological and physiological cases: metaplasia
Metaplasia: reversible change from one cell type to another, protective to the stress.
Mechanism:Genetic reprogramming of stem cells, not transdifferentiation of mature cells. If it persists, may predispose to neoplastic transformation (sq-lung)
- most commonly involves surface of epithelium
example: Barrett esophagus: esophagus lined by squamous epithelium vs stomach lined by columar epithelium (better at handling acid) = esophagus will change cell type in acid reflux (GERD); secondary example is with smoking in the lungs
can progress to cancer
** EXCEPTION: apocrine metaplasia does not increase risk for cancer (fibrocystic change in the breast) **
Example: Vitamin A deficiency (risk for night blindness) also necessary for proper maturation of the immune system and epithelium
conjutiva of the eye
(promytocytic leukemia)
Mesencymal (connective) tissue can undergo metaplasia:
- Example: myositis ossificans: trauma of the skeletal muscle
Describe the adaptive changes cells and tissues undergo in pathological and physiological cases: dysplasia, aplasia, hypoplasia
Dysplasia: disordered cellular growth, refers to proliferation of precancerous cells (eg. CIN). Arises from longstanding pathologic hyperplasia or metaplasia
** DYSPLASIA IS REVERSIBLE, once the stress is removed **
Aplasia: failure of growth during embryogenesis (unilateral renal agenesis = 1 kidney)
Hypoplasia: decrease in cell production during embryogenesis, results in relatively small organ (example: streak ovary in Turner Syndrome)
Describe the hypoxia cell injury process
Hypoxia: (oxygen deprivation) final electron acceptor in the electron transport chain, so lack oxygen = low ATP = cellular injury [most common type of injury]
Ischmia: decreased blood flow through an organ can occur through decrease in artery perfusion (example atherosclerosis) and vein drainage (** bud chiari syndrome - thrombosis of the hepatic vein infarction in the liver, most commonly caused polycythemia vera, other cause lupus anticoagulants **) or even systemic (shock)
Hypoxemia: low partial pressure of O2 in blood PaO2 < 60mm, SaO2 <), diffusion defect, V/Q mismatch (blood bypasses oxygenated lung)
Decreased O2 carrying capacity arises with hemoglobin (Hb) loss or dysfunction
Anemia (decrease in RBC mass); PaO2 normal, SaO2 normal
**Carbon monoxide poisoning (CO binds hemoglobin more avidly (100x more) than O2, SaO2 decreased, PaO2 normal), common exposure from smoke fires, exhaust from cars or gas heaters; classic finding skin is cherry red and early sign is a headache it can lead to coma and death **
**Methemoglobinemia: Iron in heme is oxidized to Fe3+ which cannot bind O2 (Fe2+ binds O2) seen with oxidant stressors (sulfa and nitrate drugs) or in new borns
Classic finding: cyanosis with chocolate-colored blood
Treatment: IV methylene blue **
Why does Low ATP disrupt key cellular functions?
Na - K pump (requires ATP): if not function Na is retained and cell will swell as water is pulled into the cell
Ca pump: is kept low in the cystol, and if low ATP it will build and it will activate enzymes that shouldn’t
Aerobic glycolysis: low ATP would lead to increase in lactic acid via anaerobic glycosis and decrease the pH would cause precipitation of DNA and enzymes
Initial phase of injury / signs to a cell:
reversible = cellular swelling (hallmark sign) and leads to loss of microvilli; membrane blebbing, and swelling of RER (ribosomes pop off with decrease of protein synth)
Irreversible damage of a cell:
Irreversible: membrane damage (hallmark sign):
Discuss membrane damage to the plasma membrane, inner mitochondrial membrane, and lysome membrane
Plasma membrane: enzymes leak out into the blood stream ie cardiac infarction, blood draw can be tested for cardiac enzymes showing irreversible damage; calcium can rush once membrane is damaged
Inner mitochonral membrane: location of electron transport chain, once damaged is irreversible; cytochrome C is in the inner mitochondria and if it leaks out it will activate apoptosis
Lysome membrane: if damaged hydrolytic enzymes leak into cytosol
Describe cell death signs:
Cell death = loss of nucleus (morphologic hallmark)
pyknosis (nucleus shrinks down), karyorrhexis (nucleus breaks up into big pieces), karyolysis (broken into basic components)
Describe necrosis:
Necrosis: is always pathologic (murder!)
- death of a large group of cells followed by acute inflammation
- hallmark: eosinophilia - increased “pink” on H&E, myelin figures, calcification of fatty acids, breaking apart of the nucleus karyolysis = pyknosis = karyorrhexis
What is cogaulative necrosis?
Coagulative necrosis: tissue remains firm and shape and organ are preserved by coagulation of cellular proteins, nucleus disappears, SEEN WITH ISCHEMIA of any organ EXCEPT the brain
- area of infarcted tissues is often wedge shaped (wedge points to the point of occlusion) and pale
Red infarction: arises if blood re-enters and tissue is loosely reorganized (testicular - vein gets blocked, but blood still flows in through the artery and pulmonary)
What is liquefactive necrosis?
Liquefactive necrosis: necrotic tissue that becomes liquefied (enzymatic lysis of cells and protein results in liquification)
- brain infarction: proteolytic enzymes from microglial cells liquify brain) - abcess: proteolytic enzymes from neutrophils - pancreatitis: proteolytic enzymes from pancreas liquify the parenchyma
What is gangrenous necrosis:
Gangrenous necrosis: coagulative necrosis that resemble mummified tissue (multiple layers) (dry gangrene)
- characteristic of ischemia of lower limb and GI tract
- if superimposed infection of dead tissues occurs then liquefactive necrosis ensues (wet gangrene)
What is caseous necrosis:
Caseous necrosis: soft friable necrotic tissue with “cottage cheese like” appearance, combination of coagulative and liquefactive necrosis
- characteristic of granulomatous inflammation due to TB or fungal infection
What is fat necrosis:
Fat necrosis: necrotic adipose tissue with chalky-white appearance due to deposition of calcium // very purple on H&E stain
- characteristic of fat trauma (breast) and pancreatitis-mediated damage of peripancreatic fat (can present as a mass)
** saponification: fatty acids released by trauma or lipase join with calcium - example of dystrophic calcification, normal serum calcium and phospate **
metastatic calcification occurs with high serum calcium or phosphate levels lead to calcium deposition in normal tissues (hyperparathydroidism leading to nephrocalcinosis)
Fibrinoid Necrosis:
necrotic damage to blood vessel wall, leaking of protein (including fibrin) into the wall (bright pink staining)
- characteristic of malignant hypertension (medical emergency - very high blood pressure) and vasculitis
- *30 y/o women with fibroid necrosis? pregnant with pre-eclampsia of the placenta
Describe apoptosis
Apoptosis: can be a normal function or pathologic (cellular suicide!)
- energy dependent genetically programmed cell death (single or small groups of cells)
example: endometrial shedding during menstrual cycle, removal of cells during embryogensis (formation of individual toes and fingers), CD8+ T cell-mediated killing of virally infected cells
Morphology: apoptosis means falling of leaves: cell shrinks (becomes eosinophilic, nucleus condenses and fragments, apoptoic bodies fall from cell and are removed by macrophages (not followed by inflammation)
provide examples of physio and patho causes of apoptosis
Physiologic
• Embryogenesis
• Hormone-dependant tissues, eg endometrium
• Cell loss in proliferating tissues (thymus, bone marrow)
• Eliminate self reactive lymphocytes
• Programmed death: neutrophils- served purpose
Pathologic (genetically altered) • DNA damage: radiation, cytotoxic drugs, hypoxia, temperature extremes • Accumulation of misfolded proteins • Cell injury from infections (viral) • Organ atrophy post obstruction
Discuss the morphology of reversible injury:
Cellular swelling:
Failure of ion pumps in plasma membrane
Organ level: pallor, increased weight
Microscopic: hydropic change or vacuolar degeneration
Fatty change:
Hypoxic, toxic, or metabolic injuy
Lipid vauoles in cytoplasm (cardiac or hepatocytes)
Ultrastructural:
blebbing, mitochondia, ER dilation
What happens with the aging process to the cells that can be pathological:
Telomere shortening (wear and tear, stem cells//RNA repair)
What is apoptosis mediated by? Describe how this mediator is activated:
** Apoptosis is mediated by caspases which activates proteases break down the cytosketeon and endunucleases breakdown DNA**
Caspases activation:
Intrinsic mitochondrial pathway: cellular injury, DNA damage, or decreased hormonal stimulation inactivates Bcl2
** cytochrome C resides in inner mitochondrial matrix, Bc12 (regulates cytochrome C) gets knocked out then cytochrome C can leak out and activate caspases driving apoptosis **
Extrinsic receptor ligand pathway: something is binding to the outside of the cell
example: FAS ligand binds FAS death receptor (CD95) - T cells born in the bone and goes the thymus to get educated and gets tested: (+) selection - Do you have the ability to bind self-antigen and MHC; (-) selection to strongly binding self-antigen, if yes it is destroyed
Cytotoxic CD8+ T cell mediated pathway: recognizes antigen and secretes perforins, granzyme from CD8+T enters pores and activates caspases
