Pathology Flashcards
The 3 major definitions of pathology are:
- The scientific and medical discipline (science) that studies the functional, molecular, and functional manifestations of disease, and the mechanisms that cause disease. 2. The structural and functional manifestations of a disease. 3. A disease.
Role of pathologists in a research setting
Pathologists advance knowledge and understanding of disease
Role of pathologists in a clinical setting
Pathologists apply knowledge and understanding of disease to optimize prevention, diagnosis, and treatment of disease.
What is a disease?
Molecular, cellular, tissue, organ, and organismic damage caused by an etiology and mediated by pathogenic mechanisms.
Where do we target prevention and treatment of disease?
Etiology (cause) Pathogenesis (mechanism of disease)
VINDICATE nemonic
V-vascular I-inflammatory N-neoplastic D-drug/toxin I-infectious C-congenital/genetic A-autoimmune/immune T-traumatic/physical E-endocrine/metabolic/nutritional
Diagnosis:
The name for a disease
Etiology:
The cause of disease (many categories: infections, physical, chemical, genetic, immune, etc.)
Pathogenesis:
The sequence of events that leads from the etiology to the manifestations of the disease
Symptom:
Disease manifestation perceived and reported by the patient
Sign:
Manifestation of disease that can be identified by physical examination, laboratory tests, imaging studies, and other methods
Differential Diagnosis:
A ranked list of the most likely diagnoses based on the signs and symptoms of disease in a given patient.
Hypertrophy:
increased size of cells
Hyperplasia:
Non-neoplastic increase in the number of cells in an organ or tissue
Atrophy:
Reduced size of cells or organs
Metaplasia:
A conversion of one differentiated cell type to another
Dysplasia:
Disordered growth and maturation of the cellular components of a tissue. Dysplasia may be a precursor to malignant neoplasia.
Neoplasia:
The autonomous growth of cells that have escaped normal regulation of cell proliferation. Neoplasms that remain localized are termed benign, whereas those that spread (or are capable of spreading) to different sites (metastasize) are termed malignant.
7 Causes (etiologies) of Atrophy:
- Reduced functional demand (e.g. skeletal muscle atrophy caused by denervation) 2. Inadequate oxygen supply (e.g. kidney atrophy caused by renal artery stenosis) 3. Insufficient Nutrients (e.g. skeletal muscle and fat atrophy caused by starvation) 4. Interrupted Trophic Signals (e.g. endometrial atrophy after menopause) 5. Persistent Cell Injury (e.g. gastric mucosal atrophy caused by chronic gastritis) 6. Increased Pressure (e.g. localized skin atrophy caused by prolonged bed rest) 7. Chronic disease (e.g. cachexia caused by chronic disease)
Apoptosis:
Cell death caused by activation of internal molecular pathways leading to cell death. Can be physiological (epithelial sloughing before renewal) or pathological (hepatitis virus-induced hepatocyte loss)
Necrosis:
Cell death caused by pathological lethal injury that often originates outside the cell (e.g. injury by hypoxia, inflammation, molecular toxin, burn, etc.)
How is cell death histologically demonstrated?
Nuclear changes
Pyknosis:
The nucleus becomes smaller and stains deeply basophilic because of chromatin clumping
Karyorrhexis:
The pyknotic nucleus breaks up into many smaller fragments
Karyolysis:
The nucleus may be extruded from the cell or have progressive loss of chromatin staining resulting in the disappearance of the nucleus
Coagulative necrosis:
Nuclei disappear (karyolysis) and cytoplasm becomes more homogenous (and often more acidophilic) resulting in residual ghosts of cells with no nuclei. (e.g. can emerge with MI with ischemic coagulative necrosis)
Gross features:
e.g. localized discoloration of the myocardial tissue caused by ischemic necrosis
Histologic features:
e.g. localized discoloration on the myocardial tissue with loss of myocardial cell nuclei (karyolysis)
Liquefactive necrosis:
Rapid dissolution of cells that liquefies the necrotic tissue. Most often caused by intense localized infiltration of neutrophilic polymorphonuclear leukocytes (neutrophils) at sites of severe acute inflammation (e.g. caused by bacterial infection). Localized acute inflammation with liquefactive necrosis is called an abscess.
Caseous Necrosis:
Necrosis caused by tuberculosis with a marginal zone of aggregated macrophages and a central zone of necrosis containing amorphous debris derived from necrotic hose cells and necrotic mycobacterial cells. The nodular gross lesions are called granulomas and the dense infiltrates of macrophages granulomatous inflammation.
Fat necrosis:
Specifically affects adipose tissue and most commonly results from pancreatitis or trauma resulting in the release of lipases that free up fatty acids that bind calcium to form calcium soaps (saponification).
Tissue response to injury:
Begins with etiology Cell/issue injury Acute inflammation Chronic inflammation Repair (regeneration and/or fibrosis) *not every injury results in the full spectrum of responses
Inflammation:
A reaction of tissue to a pathogenic insult. Mediated by extracellular molecular signals that activate humoral and cellular inflammatory pathways, and cause the movement of fluid and leukocytes from blood into the extravascular compartment
Result of inflammation:
-Localizes or eliminates the cause of injury -Removes injured tissue components -Leads to repair *Inflammation is a double-edged sword that usually is beneficial but can cause morbidity and mortality.
Five cardinal signs of acute inflammation:
- Rubor (redness) 2. Tumor (swelling) 3. Calor (heat) 4. Dolor (pain) 5. Functio Laesa (loss of function)
Acute inflammation:
Has densely packed polymorphonuclear neutrophils (PMNs) with multi-lobed nuclei -Vasodilation resulting in increased blood flow causing redness and transudation of fluid causing edema. -Activation of humoral mediators, causing pain, exudation of plasma proteins, and transmigration of neutrophils. -Influx of numerous mononuclear leukocytes (lymphocytes, monocytes, macrophages, plasma cells) -Increased extracellular matrix (collagen)
Chronic inflammation:
has mononuclear leukocytes, monocytes, macrophages, and plasma cells
Transudate:
ADD
Exudate:
ADD
Mononuclear leukocytes:
lymphocytes, monocytes, macrophages, plasma cells
Hemosiderin
ADD
Purulent exudate
Pus
Granulation tissue
Part of the repair process where new tissue is growing after injury.
Healing Process:
- Incision with hemorrhage 2. coagulation stops hemorrhage 3. neutrophils enter site 4. monocytes enter site 5. monocytes transform into macrophages that are phagocytic and secrete cytokines that attract lymphocytes 6. growth/proliferation factors produced by lymphocytes, macrophages, fibroblasts and endothelial cells mediate 7. endothelial cells proliferate to form new capillaries to supply oxygen and nutrients for repair 8. Granulation tissue - capillaries formed in young fibrous tissue 9. scar (residual excess collagen at site of injury)
What occurs during incision with hemorrhage?
Injury initiates a response to injury that leads to complete restitution of tissue or chronic changes such as scarring
Describe early events of coagulation:
Humoarl (e.g. coagulation) and cellular (e.g. platelet, mast cell, neutrophil, and endothelial) activation Mast cell degranulation
Neutrophils and healing:
Neutrophils follow chemotactic gradients to sites of injury
Granulation tissue:
Young stage of repair with new capillaries in young, fibrous tissue
Describe the stages of damage/healing in a heart after MI
- coagulative necrosis develops about 12 hours after lack of oxygen, resulting in karyolysis. 2. After 24 hours, see effects of acute inflammatory response - see lots of neutrophils in the tissue mixed among dead myocytes 3. 3 weeks later, we see that the inflammatory process progressed from acute to chronic and into repair phase. See granulation tissue, characterized by fibroblasts, new vessels, loose connective tissue, and a few chronic inflammatory cells. 4. About 3 months later, see fibrous scar resulting from laying down of collagen
_______ caused by cell/tissue injury can contribute to long term morbidity (dysfunction)
Fibrosis
Thrombosis:
Occurs when endothelial function is altered, endothelial continuity is lost, or blood flow is reduced. Involves activation of circulating platelets and coagulation factors.
Inadequate thrombosis causes _______ _______.
Hemorrhagic diseases
Thrombosis that obstructs adequate flow causes ______ ______.
Ischemic diseases.
Embolization causes ________ ______.
Thromboembolic disease.
Possible causes of DVT:
- Stasis (most common) 2. Vascular injury 3. Hypercoagulability 4. Advanced age 5. Sickle cell disease
Possible outcomes of DVT:
- Lysis 2. Propagation 3. Organization 4. Recanalization 5. Embolization
Propagation of thrombus:
Can get bigger
Organization of thrombus:
Endothelial cells grow over it, fibroblasts generate collagen around it, and can become a permanent plug in the vein
Recanalization of thrombus:
New blood cells may generate to allow flow through the plug
_______ is a blood test that measures the time it takes for blood to clot.
Partial thromboplastin time (PTT) test
PTT test is used to:
-Find a cause of abnormal bleeding or bruising -Check for low levels of blood clotting factors that may cause bleeding disorders such as hemophilia -Check for conditions that cause excess clotting problems, thrombophilia -Check if it is safe to do a procedure or surgery that might cause bleeding -Check to see how well the liver is working
ADPKD
Autosomal dominant polycystic kidney disease - caused by mutations in genes for proteins involved in primary cilium function, cell cycle regulation, and intracellular calcium transport in epithelial cells. -Characterized by fluid filled spaces and very little normal kidney tissue (nonfunctional kidney)
Agenesis:
complete absence of an organ or component of an organ (e.g. renal agenesis = no kidney)
Aplasia:
Persistence of an undeveloped organ anlage without the mature organ (e.g. renal aplasia - could be like a ball of tissue where the kidney should be with normal kidney precursor cells under scope, but non-functional
Hypoplasia:
Reduced size caused by incomplete development (e.g. microcephaly - normal organ with normal structure and function, but smaller)
Atresia:
Incomplete function of a lumen (e.g. esophageal atresia)
Dysplasia:
Abnormal tissue differentiation during development (distinct from dysplasia developing in a previously normally developed tissue) - e.g. renal dysplasia = tissue initially developed normally and then underwent change during developmental process, so kidney has components that should be there, but differentiation is incorrect and this is a disorganized mass of kidney tissue that can’t function
Ectopia:
Normally formed organ that is outside its normal anatomic location (e.g. ectopic kidney)
Zika virus infection of fetal neural stem cells causes inhibition of the ______ pathway
Akt-mTOR
Cystic fibrosis is characterized by:
-Chronic pulmonary disease -Deficient exocrine pancreatic function -Other complications of inspissated (thick) mucus in multiple organs, including the small intestine, liver, and reproductive tract
What are the cells on the top?
What are the cells on the bottom?
Top: normal hepatocytes
Bottom: Hepatocytes with abnormal swelling because of increased water within organelles (hydropic change) caused by injury by a toxin - this is a biopsy of a liver with acute drug toxicity.
**This cell swelling is irreversable
What is the difference between the cells on the left vs. the cells on the right?
The cells on the left are normal cardiomyocytes.
The cells on the right are hypertrophied cardiomyocytes. (Note that the nuclei are also enlarged along with the enlarged size of the cells)
What has happened to the cells in this photo?
This is an example of hyperplasia.
We see an increase in the squamous cell epithelium, but the cells are still organized and have not undergone a cell type change.
What are the labeled cells on the left vs. the right?
The pink circle of cells is an example of a squamous metaplasia
The labeled cells on the right are the normal columnar epithelium.
What is shown in this slide?
This slide of the uterine cervix epithelia shows dysplasia.
On the left are the normal cells, which in this area have normal squamous cells at the base and cells with polarity and some loss of nuclei on top.
On the right is unpolarized dysplastic epithelium (we see nuclei all the way to the surface, which is abnormal for this body area)
What is shown in this slide?
On the left are normal myometrium cells.
On the right is an example of a benign leiomyoma
What is shown in this slide?
This is a malignant leiomyosarcoma.
In general, malignant neoplasms have less well differentiated cells that have larger nuclei that are pleomorphic, atypical, hyperchromatic, and more often undergoing mitosis.
A 40 year old woman developed Cushing Syndrome (signs and symptoms caused by prolong exposure to excess cortisol). An adrenal gland tumor was removed surgically (shown). Based on your understanding of neoplasia, what is the most likely diagnosis?
Benign adrenal adenoma
(There is an increased number of cells, but because it has formed the nodule of new growth with abnormalities, it is an adenoma). The cells themselves are in excess, but appear structurally normal.
What is happening in this cell?
Apoptosis
(Characteristic appearance - apoptotic bodies with condensed and fragmented nucleus. Can be localized as a single cell process surrounded by normal cells)
What is shown in this slide?
Coagulative necrosis
The nuclei have disappeared (karyolysis) and the cytoplasm is more homogenous and often more acidophilic, resulting in residual ghosts of cells with no nuclei.
These cells are from a biopsy of an MI with ischemic coagulative necrosis.
What is shown in this slide?
Liquefactive necrosis
The center of this slide shows an abscess containing numerous neutrophils (pus, purulence) that have liquefied the tissue.
What is shown in this slide?
Caseous Necrosis
(Caused by tuberculosis with a marginal zone of aggregated macrophages and a central zone of necrosis.)
This photo shows caseous necrosis in the middle surrounded by granulomatous inflammation
(NOTE: the nodular gross lesions are called granulomas)
What is shown in this slide?
Fat necrosis
Shows affected adipose tissue were fatty acids have bound calcium to form calcium soaps (saponification).
This normally occurs in the vicinity of the pancreas, as a result of the release of pancreatic enzymes into the tissue instead of the bile.
Note loss of all histologic detail.
What is shown in this slide?
Acute inflammation
Note the densely packed polymorphonuclear neutrophils (PMNs) with multilobe nuclei
What is shown in this slide?
Chronic inflammation
Note the mononuclear leukocytes including lymphocytes, monocytes, macrophages, and plasma cells.
What is shown in this slide?
Nodules of regenerating hepatocytes
Blue areas show fibrosis
What is shown in this slide?
Cystic fibrosis lung feat. thick mucus plug in bronchial airway
What is shown in these slides?
The top slide shows a normal pancreas
The bottom slide shows a cystic fibrosis pancreas, with a cyst and example of fibrosis labeled
What is shown in this slide?
This slide shows normal breast tissue, with gland tissue in the center.
What is shown in this breast biopsy?
In this breast tissue biopsy there are a significant number of gland cells (hyperplasia) but the organization is still there - this is normal in a pregnant woman’s breast biopsy, because gland cells are increasing in preparation for lactation.
Metaplasia of the bronchial epithelium of this patient is:
A reversible adaptation to harmful components in smoke
[We no longer see the pseudostratified ciliated epithelium characteristic - this is a normal, reversible response by the body to try to create a more robust cell type along the lining and prevent excessive smoke/toxin absorption]
What is shown in this lung biopsy?
This slide shows a squamous cell carcinoma. [The growth looks very disorganized - we used to have a lining on the surface, and now a surface isn’t even detectible. This diving into the tissue is an invasive malignancy.]
The darker areas are the neoplatic cells, and the lighter regions are areas of fibrosis.
What is shown in this slide of debrided tissue?
Granulation tissue
[Lots of nuclei - they look different, which tells us that there are lots of different kinds of cells (neoplasms tend to have nuclei with similar structures because it’s caused by rapid cloning] Granulation tissue is a normal effect of healing.
The formation of capillaries in healing tissue is most directly associated with proliferation of which cell type?
Endothelial cells
The repair of necrosis in the heart is very different from that in the liver because of:
The different proliferative capacity of cells - brains and heart are post-mitotic and can’t divide extensively after cell loss. The liver can keep dividing but is limited by the environment where it’s dividing.
CF Screening Stage 1:
Immunoreactive trypsinogen (IRT) level:
- early indicator of CF (sensitivity 80-90%)
- Pancreatic enzyme precursor
- Elevated when pancreas is damaged
- Highest 5% of patients go to stage 2
CF Screening Stage 2:
Molecular testing for 40 common CF mutations: (sensitivity 95%). If a mutation is identified, reported as “abnormal for CF” to healthcare provider. Patient can undergo sweat testing at UNC-CH
Sweat testing:
Pilocarpine stimulates sweating when applied to skin. Patient with CF have elevated sweat chloride concentration.
- The most common mutation is DF 508
What is shown in this slide of a bronchiole?
This slide shows large amounts of neutrophilic exudate in the bronchiole. This is an autopsy slide taken from a CF patient - basically a ton of pus/fluid in the airway
What are A, B, and C in this slide of a CF patient’s pancreas?
A: acini with marked necrosis,
B: distended ducts with viscid secretions,
C: Fibrotic bands encasing damaged exocrine elements (characteristic of chronic pancreatic injury)
What is the function of the CFTR gene product?
A cAMP regulated chloride channel
Essentially all the pathophysiology associated with CFTR defects can be most directly explained by what?
Decreased hydration of mucus secretions
