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)
