Flashcards in General Pathology Deck (69)
Deeply eosinophilic cytoplasm, cell shrinkage and basophilia with membrane blebbing
Look for nuclear fragmentation and formation of apoptotic bodies as well.
BAX and BAK are both what sort of proteins?
What about Bcl-2?
BAX and BAK are both pro-apoptotic from the mitochondria.
Bcl-2 is antiapoptotic and prevents cytochrome c release by binding to and inhibitin Apaf-1
Describe the intrinsic pathway of apoptosis.
Bcl-2 is inhibited leading to the release of BAX and BAK.
BAX and BAK act at the mitochondria to release cytochrome c. Cytochrome c carries out cytosolic caspaces that break down the cell.
Describe the extrinsic pathway of apoptosis
Ligand receptor interactions FasL binding to Fas (important in the thymus for negative selection)
Cytotoxic T cells releasing perforin and granzyme B
Ischemia and infarcts in most tissues except the brain.
Cell outlines are generally preserved by cytoplasm will bind to acidophilic dyes.
Seen in bacterial abscesses and brain infarcts due to high fat content.
Done by neutrophils* releasing lysosomal enzymes into the tissue.
Seen with tuberculosis and systemic fungi.
Macrophages wall of the infecting organism.
Enzymatic due to acute pancreatitis.
The damaged cells release lipase which leads to fatty acid break down in cell membranes.
Immune reactions in blood vessels.
The immune complexes bind fibrin within the vessels.
Distal extremities after chronic ischemia.
When wet it is considered a super infection and is liquefactive.
What type of necrosis is seen in wet gangrene?
When dry it is considered coagulative (the go to)
Which area in the liver is most suceptible to ischemia?
Zone 3 as its furthest from the blood supply.
What is a red infarct?
Hemorrhaigic occuring in venous occlusion with multiple blood supplies.
Be careful with reprofusion as it can lead to a reprofusion injury when free radicles from the circulation are sent to the tissue
What is a pale infarct?
Pale infarcts are due to ischemia in organs tha thave only single ended blood supplies such as the heart, kidney, and spleen.
5 cardinal signs of an infection?
Loss of function
Acute inflammation includes...
Neutrophils and eosinophils. IgM plays a role as well.
Chronic inflammation includes...
Mononucear cells and fibroblasts
You will find persistant destruction and repair cycles.
You see a neuron that has round cellular swelling, the nucleus has been displaced to the periphary and there is a ton of Nissl substance in the cytopasm... this is highly indicative of?
Highly indicative of a neuron that has undergone damage and is attempting to repair itself.
The cell body ramps up its protein production in an effort to repair its damaged axon.
Calcium deposition in abnormal tissues secondary to injury or necrosis.
Serum calcium levels will be normal and this is key.
Widespread deposition of calcium in normal tissue secondary to hypercalcemia or high calcium-phosphate product.
Serum calcium levels will not be normal in these patients.
ICAM-1 and VCAM-1 are important for what cellular action?
These two are expressed on the vasculature and are important for the tight binding step during extravasation.
they bind onto integrins.
PECAM-1 is important for what cellular action?
The PECAMS bind eachother during extravasation and allow for diapedesis (WBC travels between the endothelial cells)
E selectin and P selectin as well as GlyCAM-1 are important for which cellular function?
These are cell surface molecules that interact with the selectins of WBC for margination and rolling durin leukocyte extravasation.
How long does it take until a scar has regained 70-80% of its tensile strength?
Very little tensile strength will be regained after that time.
What does the tissue mediator PDGF do when involved in wound healing?
It is secreted by platelets and macrophages inducin vascular remodeling and smooth muscle cell migration.
Stimulates fibroblast growth for collagen synthesis.
What does the tissue factor FGF do when involved in wound healing?
FGF stimulates angiogenesis
What does the tissue factor EGF do when involved in wound healing?
EGF stimulates cell growth via tyrosine kinases
What does the tissue factor TGF-B do during wound healing?
Angiogenesis, fibrosis, cell cycle arrest.
What do metalloproteinases do during wound healing?
What does VEGF do during wound remodeling?
Keep in mind that FGF does as well.
What is occurring 3 days following a wound
Platelets, neutrophils and macrophages are present.
Clot formation is occuring and vascular permeability is increasing.
Macrophages clear the debris at 2 days.
What is occurring 3 weeks after wound?
Three weeks following the wound there is proliferation occuring.
Fibroblasts and myofibroblasts as well as endothelial cells and keratinocytes are depositing granular tissue and collagen.
Angiogenesis is occuring as well with epithelial cell proliferation and wound contraction.
What is occuring 1 week to 6+ months following a wound
This is the remodeling phase in which fibroblasts are laying down
TYPE III collagen!
Will be replaced by type 1 collagen allowing increased tensile strength
What collagen replacement leads to increased tensile strength?
Replacement of collagen type 3 with collagen type 1 during the remodeling phase of wound healing (1 week - 6 months)
How do T-cells induct granulomatous lesions?
By releasing IFN gamma they activate macrophages to wall off the infection.
TNF alpha from the macrophages then retains the granuloma formation.
Which drugs should be avoided in patients suffering from granulomatous diseases?
Anti TNF alpha drugs can dispurse the macrophages that are walling off the macrophages leading to disseminated disease. Always test for latent TB before initiating anti-TNF therapy.
Whats the diffference between an exudate and a transudate?
Exudates are thick, cellular, and protein rich. Typically due to a lymph obstruction, inflammation, or malignancy.
Transudates are thin hypocellular and protein poor.
Typically due to an increase in hydrostatic pressure seen in heart failure and decreased oncotic pressures seen in cirrhosis or nephrotic syndromes.
How does sedementation rate tests work?
Products of inflammation (fibrinogen) bind to RBC making them heavy.
ESR tests how quickly affected blood cells fall in a pippete.
thus high ESR's will be with infections, anemia, inflamation and cancer.
Low ESR would be with sickle cell anemia, polycythemia, heart failures and microcystosis.
What type of sheets are amyloid sheets?
Beta pleated sheats. Leads to cellular damage and apoptosis.
Most important form of amyloidosis is alzheimer disese due to beta-amyloid protein being cleaved from the precursor proteins.
Congo red staining showing apple green birefringes under polarized light
A sign of amyloidosis.
what is lipofuscin?
A wear and tear pigment associated with normal aging.
What are the 5 steps of cancer metastasis?
Hyperplasia Cells increase in number. Dysplasia is the abnormal proliferation of weird/abnormal cells.
Carcinoma in situ: Preinvasive cells/ havent passed the basement membrane yet.
Invasive carcinoma: Cells have passed the basement membrane using collagenase and hydrolases. E cadherins are destroyed.
Metastasis: Spreads to distant organ via the Seed (tumor embolus) and soil (target ogan first contacted by bed)
Also known as multidrug resistant protein 1 (MDR1)
Classicaly seen in adrenal cell carcinoma used to pump out toxins by cancer cells.
Increased number of cells.
Dont confuse it with hypertrophy which is increased cell size,
One adult cell type has switched to another. Usually secondary to irritation as seen in barrets esophagus.
Abnormal growth with loss of cellular orientation, shape, size.
Loss of structural differentiation and function of cells.
Cells begin resembling primative cell types. May see giant cells here.
An uncontrolled and excessive clonal proliferation of cells. May be benign or malignant.
Fibrous tissue formation inresponse to a noplasm
What is a tumor grade?
The degree of cellular differentiation and mitotic activity on histology.
What is the tumor stage?
Tumor stage is the degree of localization/ spread based on the tissue site and size.
T = Tumor size
N = Node involvement
M = Metastases
Define the difference between carcinoma and sarcoma
Carcinoma is epithelial origin
Sarcoma is mesenchymal origin.
Both terms imply malignancy.
what is cachexia?
Weight loss, muscle atrophy and fatigue during chronic diseases.
Mediated by TNF alpha (cachectin)
Precursor to squamous cell carcinoma of the skin
Precursor to malignant melanoma
L-myc gene mutation
N-myc gene mutation
BRCA1 BRCA2 gene mutation
Breast and ovarian cancer
NF1 and NF2
Neurofibromatosis type 1 and type 2
RB gene mutation
WT1/WT2 gene mutation
Wilms tumor (Nephroblastoma)
CEA tumor markeer
Very non specific but produced by 70% of colorectal and pancreatic cancers.
PSA tumor marker
Prostate specific antigen can be elevated in prostatitis and prostate cancer.
Excessive ACTH production
Excessive ADH production
These are laminated, concentric spherules with dystrophic calcification.
Seen in papillary carcinoma of the thyroid
Serous papillary cystadenocarcinoma of the ovary.Meningioma
Top three most common cancers in men and women
Men: Prostate,Lung, colon/rectum
Females: Breast, Lung, Colon/rectum
Top three cancers for mortality in women and men
Men: Lung, Prostate, Colon/rectum
Women: Lung, Breast, Colon/rectum