Pathology: Adaptation, Injury, Death (Part 1) Flashcards
Define adaptation.
the set of physiologic and morphologic changes, modulating a person/organ/cell, bringing it into a new altered steady state of homeostasis, which can usually be sustained indefinitely.
Define hypertrophy.
adaptation to increased workload; results from cell size growth (not increased number of cells)
Define hyperplasia.
increased number of cells in an organ that frequently occurs with hypertrophy but doesn’t have to
Define atrophy.
decrease/shrinkage in the size of an organ or tissue
Define autophagy.
the process by which a cell digests its own organelles or large protein aggregates during atrophy or for recycling
Define steatosis.
the accumulation of excess lipid in cell cytoplasm, primarily in hepatocytes; also called fatty change
Define metaplasia.
The replacement of one tissue with another fully differentiated tissue but abnormal for that site; pretty much always pathologic and reversible. Your body’s natural response to a change in the type of stress. eg. Barrett’s esophagus.
Explain the principle of Occam’s razor.
“assume there is only one explanation and do not think there are 2/more, unless you have to”; in medicine this means that a single diagnosis that explains everything is most likely the right diagnosis
Explain the principle of Hickam’s dictum.
“a patient can have as many diseases as he darn well pleases”; the older the patient, the more likely to have multiple diseases
What is hemosiderin and what is its significance/usefulness?
hemosiderin is the term for intracellular aggregates of ferritin micelles, this is a storage form of iron from hemoglobin breakdown
What is lipofuscin and what is its significance/usefulness?
lipofuscin is a light brown-colored pigment that consists of peroxidized lipids from the membrane complexed with protein; results from a atrophied cell; also known as wear-and-tear pigment
What is injury?
reversible patholophysiologic/morphologic response to a stress or noxious stimulus that exceeds the ability to adapt
Death of an organ/tissue is called ____.
necrosis
Lesion is a term for a …
…discrete visible manifestation of disease.
The cause of a disease is referred to as ____.
etiology
What are the 8 categories in classification of disease?
V - Vascular I - Infectious T - Toxic/Traumatic A - Autoimmune M - Metabolic I - Idiopathic (+degenerative) N - Neoplastic D - Development (+genetic)
What are the ten aspects for study of a disease?
- Definitionfac
- Epidemiology
- Pathology
- Gross pathology
- Microscopic pathology
- Symptoms
- Signs
- Diagnosis
- Treatment
- Prognosis
When mechanical stretch receptors in muscles are stimulated by increased workload, they induce increased levels of growth factors. What are these growth factors?
- transforming growth factor-beta
- insulin-like growth factor 1
- fibroblast growth factor
When mechanical stretch receptors in muscles are stimulated by increased workload, they induce increased levels of vasoactive agents. What are these vasoactive agents?
- alpha-adrenergic agents
- endothelin-1
- angiotensin II
Growth factors stimulating muscle growth based on workload act through what signal transduction pathway?
PI3K/AKT pathway, which activates TFs MEF2, GATA4, and NFAT
How does natriuretic peptide lessen the workload on the heart?
it causes the kidneys to excrete more salt, which decreases blood volume and thereby blood pressure
* Na(sodium) + uresis(out) = natriuretic peptide
With hemorrhage or hemolysis, the hormone ____ causes hyperplasia of the blood-producing bone marrow as much as __-fold.
erythropoietin; 8-fold
Some HPVs cause warts. What is the pathophysiology of this development?
the virus infects skin and mucous membranes, causing hyperplasia; the resulting hyperplasia is a wart
What are the causes of pathologic atrophy?
- disuse
- denervation
- ischemia
- starvation
- pressure
- endocrine
Cells undergoing atrophy break down their proteins via the ___-____ pathway.
ubiquitin-proteasome
Cells undergoing atrophy break down their membranous constituents via ____.
autophagy
What are Hamazaki-Wesenberg bodies?
these are residual bodies (large membrane-bound piles of cellular debris that remain after a cell dies) that are taken up by professional phagocytes
Describe the process of autophagy.
cells forms a phagopore isolation membrane around the organelle, forms an autophagosome which then merges with the lysosome, which digests the organelle
What are autophagy-related genes?
genes that code for proteins needed for the autophagy process; there are >12 and they are numbered
Macrophage-specific deletion of Atg-__ increases susceptibility to _____ _____, a prototype intracellular pathogen.
5; mycobacterium tuberculosis
Defective ____ is a pathophysiologic mechanism of neurodegenerative diseases such as Alzheimer’s and Huntington chorea.
autophagy
Hepatic steatosis is extremely common because it is caused by ____ and ____.
alcohol and obesity
How are hepatic steatosis and kwashiorkor starvation related?
Starvation causes lipolysis to release fatty acids from adipocytes. In kwashiokor protein deprivation is disproportionately lower than total calorie deprivation, so there is not enough protein to form lipoproteins for metabolism. Therefore the released fatty acids accumulate in hepatocytes.
Describe the mechanisms for transferring and storing Iron.
iron is transferred in the bloodstream bound to the protein transferrin; within cells iron is bound to apoferritin to form ferritin micelles; aggregates of ferritin micelles are called hemosiderin
In a bleeding event, macrophages break down the leaked RBC and remove the iron. What happens then to the heme moiety and to the iron?
Heme first converted to the green compound biliverdin, then red compound bilirubin.
Iron is incorporated into the brown hemosiderin.
What is hemosiderosis?
a condition of total body iron overload - because the body has no way of excreting excess iron but continues undergoing hemolysis (such as in sickle cell disease)
What is hemochromatosis?
genetic disease of white people which causes absorption of excess iron and the body experiences total body iron overload
What is the most frequent type of metaplasia?
replacement of columnar epithelium with squamous epithelium; can be caused by smoking or vitamin A (retinoid acid) deficiency
Why does bronchial metaplasia increase the risk of respiratory infection?
the major defense mechanism in the lungs against inhaled microorganisms is to trap them in mucous secreted by the columnar epithelium and move them up and out with ciliary beating; squamous metaplasia abolishes this defense
What are two examples of metaplasia leading to cancer?
- bronchial squamous metaplasia leading to dysplasia, then to squamous carcinoma
- GERD leading to intestinal metaplasia (barrett’s esophagus) leading to dysplasia then adenocarcinoma of the distal esophagus
What is the mechanism of most metaplasia?
reprogramming of stem cells - these are cells that are capable of dividing into: differentiated cell and replacement stem cell
What are the medically important electrolytes, in order of relative importance?
K, Na, HCO3, Cl, Ca
Low potassium is known as ___, and causes what symptoms?
hypokalemia: interferes with contractility of skeletal muscle, (commonly first symptomatic in the leg muscles), ileus/adynamic ileus/paralytic ileus (loss of normal intestinal peristalsis); more severe can cause respiratory weakness/shallow respirations and cardiac arrhythmias
What are typical, general symptoms of hyperkalemia?
mental malfunction typically manifested by confusion, nerve malfunction such as numbness, tingling, loss of deep tendon reflexes, bradycardia, muscle weakness and cardiac arrest
Which is more likely to a cause fatal cardiac arrhythmia: hypo- or hyperkalemia?
hyperkalemia
Sodium is crucial in maintaining the _____ of body fluids.
tonicity
Normal osmolality in body fluids is around ___mOsm/L, and dissolved sodium account for ___mOsm/L.
300
140
What happens to water in cells when there is a low level of sodium in the blood? In which is this result most dangerous?
water enters cells in excess, causing cellular swelling; swelling of neurons is particularly dangerous because their malfunction can result in confusion at first, then lethargy, obtundation, stupor, coma, seizures, and death
What are the nervous system changes caused by hypernatremia?
confusion, disorientation, lethargy, obtundation, coma; also depresses the respiratory center in the brain which could lead to ceasing respiration; also affects the function of nerve fibers
Cellular metabolism continuously generates ___ as a by-product, and ____ is the most important buffer in the blood as the by-product is carried to the kidney for excretion.
acid; bicarbonate (HCO3)
Acidosis is caused by what?
a build-up of acid in the body; due to deficiency of bicarbonate; most commonly caused by renal failure, excess acid production, and respiratory failure
What type of respirations would lead to alkalosis and why?
hyperventilation, because too much CO2 is excreted and results in an excess of bicarbonate
Vomiting can result in alkalosis; why?
expulsion of HCl can leave behind an excess of bicarbonate
How is blood bicarbonate measured in the laboratory?
blood sample is treated with a strong acid which breaks down the bicarbonate and liberates the contained CO2; the CO2 is measured and reported as a surrogate for bicarbonate; but there are other sources of CO2, normally they are negligible but in respiratory failure they may not be, so some medical labs have other techniques to improve the accuracy of measuring CO2 as a surrogate for bicarbonate
