Pathoma Flashcards
Describe the difference between hypertrophy and hyperplasia
Hypertrophy is the increase in gene activation, protein synthesis, and production of organelles.
Hyperplasia is the production of new cells from stem cells. Permanent cells cannot undergo hyperplasia. (Cardiac, Skeletal muscle, nerves)
How are cells decreased in size?
Ubiquitin proleosome degradation.
MetaplasiA
stress causes a change in cell type.
Barretts esophagusnon keratinized squamous to columnar in response to stomach acid.
In addition to cell stress, which vitamin deficiency can lead to metaplasia?
Vitamin A deficiency
Important in differentiation of specialized epithelial structures such as the eye.
Aplasia
Failure of cell production during enibryogenesis.
Describe the difference between slowly developing cell injury and acute injury in regard to ischemia.
Slow developing ischemia results in atrophy. Think renal artery atherosclerosis.
Acute ischemia results in cell injury (renal artery embolus)
Hypoxia
Low oxygen in the tissue.
Impairs ATP production leading to cellular injury.
Hypoxemia
Low Oxygen in the blood.
Normally it is 60 mm Hg. and 90% sat.
Think of high altitude.
Diffusion defects
V/Q mismatches
Decreased carrying capacity.
Cherry red appearance of the skin.
Carbon monoxide poisoning.
Iron in the blood is oxidized to Fe3+
Methemoglobinemia.
Seen with sulfa/nitrate drugs in new borns.
Treat with intravenous methylene blue.
Cyanosis with chocolate colored blood.
Methemeglobin
Treat with methylene blue.
What is the hallmark of reversible cellular injury?
Cellular swelling with loss of microvilli and membrane blebbing.
Think initial hypoxia.
What is the hallmark of irreversible cellular injuries?
Membrane damage.
Cytoslic enzyme leakage (cardiac troponin)
Cytochrome C leaking into cytosol from mitochondria activating apoptosis.
What is the morphologic hallmark of cell death?
Loss of the nucleus.
Nuclear condensation (pyknosis)
Fragmentation
Dissolution
Two mechanisms of cell death are necrosis and apoptosis.
Necrotic apoptosis
Necrotic tissue remains firm.
Characteristic of infarction of all organs except the brain (liquefactive)
Liquefactive necrosis
Liquid necrosis via cell lysis.
Brain lysis from microglial cells.
Abscesses from neutrophil enzymes.
Pancreatitis from pancrease enzymes.
Gangrenous necrosis
Coagulative necrosis
following ischemia of lower limb and GI.
Can be wet when there is an infection leading to liquefactive.
Caseous necrosis
Soft, cotage cheese like.
Combination of coagulative and liquefactive.
Very related to fungal infections and TB.
Fat necrosis
Chalky white necrotic adipose tissue due to calcium deposit.
Characteristic of trauma to fat. Trauma to breast etc.
Difference between dystrophic calcification and metatastic calcification.
Dystrophic occurs when there is necrosis and calcium binds to it.
Metatastic is due to excessive serum calcium levels leading to calcium deposits in normal tissue.
Fibrinoid necrosis
Necrotic damage to blood vessel wall.
Leads to exudate and bright staining of vessel wall.
Think hypertension and vasculitis.
How does the cytoplasm change with apoptosis?
Becomes eosinophilic (pink) and shrinks.
Proteins break down and the nucleus condenses.
Capsases then induce cellular injury and DNA damage.
What is the intrinsic mitochindrial apoptotic pathway?
Cellular injury, DNA damage or loss of hormonal stimulation leads to activation of Bc12.
Cytochrome c leaks out of inner mitochondrial matrix and activates capsases.
What is the extrinsic mitochondrial apoptotic pathway?
FAS ligand binds FAS death receptor on target cell activting capsases.
Tumor necrosis factor TNF can also bind leading to capsase activity.
How do CD8 cells trigger apoptosis
Perforins secreted
Granzyme enters pores from perforins and activate capsases.
how do free radicals cause cellular injury?
Peroxidation of lipids and oxidation of DNA/proteins.
What are the main antioxidants?
Glutathione
Vitamins A, C, and E.
Describe reperfusion injuries
return of blood to ischemia tissus results in the production of o2 derived free radicals that damage tissue.
Myocardial tissue will continue forming cardiac enzymes following reprofusion.
What are the common characteristics of amyloid?
Beta pleated sheets
Congo red staining
Apple-green birefringence under polarized light.
How will amyloid effect the kidneys?
Nephrotic syndrome
The kidney is the most common organ involved in amyloidosis.
What role does amylin have in type I diabetes?
Aniylin derived from insulin deposits into the beta islets of the pancrease.
Describe the role of amylin in alzhimers disease.
Amyloid deposits in the substantia nigrae (basal ganglia) in the midbrain.
What happens when a TLR is activated on a macrophage?
Leads to the upregulation of NF-kB which is a nuclear transcription factor that leads to production of immune mediators.
What role do prostaglandins have in inflammation?
Increase vascular permeability and pain.
What role do leukotriens have in inflammation?
These attract neutrophils
Mediate vasoconstriction
Bronchospasm
Increase vascular permeability.
What do mast cells release?
Histmine immediately leading to vasodilation and increased vascular permeability. (IgE)
Leukotriens are released as well in the delayed response.
Classic pathway of compliment
IgG or IgM mediated
Alternative pathway of complement
Microbrial products directly activate complement.
Mannose- binding lectin pathway
MBL binds to mannose on pathogen activating complement.
What do all three compliment pathways produce?
All three will produce C3 convertase that activate C5 .
C5 combines with 6-9 to form the MAC (attack complex)
Describe C3a and C5a
C3a and C5a both trigger mast cell histamine release.
C5a further chemoattracts neutrophils.
Hageman factor
Factor 12 relased by the liver that is activated by tissue collagen.
When activate starts coagulation and fibrinolytic systems, complement, and the kinin system.
Cardinal signs of inflammation
Rubor Calor Dolor tumor Loss of function
How is fever mediated?
Pyrogens cause macrophages to release IL-1 and TNF which increase COX activity in hypothalamus.
Raises the temp set point.
What allows neutrophils to roll?
Selectins
P-selectin = histamine
E selectin = TNF and IL-1
What allows neutrophils to perform adhesion?
ICAM and VCAM interacting with integrins.
Pt shows increased bacterial infections that lack pus, had a delayed separation from the umbilical cord at birth and increased circulating neutrophils.
Likely a neutrophil adhesion mutation in the integrins.
What enzyme allows for oxidative bursts?
NADPH interacting with O2
Chronic granulomatous disease?
Characterized by poor O2 dependent killing due to a deficiency in the NADPH oxidase defect.
Heavily suceptible to catalase positive critters!
Can test with the nitro blue tetrazolium test.
What are the antiinflamatory cytokines produced?
IL-10 and TGF
Which cytokine by macrophages recruits more neutrophils?
IL-8
Describe CD4 cell activation
APC cells present on MHCII
B7 on APC binds CD28 on CD4 cells.
What do TH1 cells secrete
CD4 cells that secrete IL-2 which is a Tcell growth factor and CD8 T cell activator.
Also secrete IFN gamma that activates macrophages.
What do TH2 cells secrete
CD4 cells that secrete IL-4 for B cel switch to IgG and IgE.
IL-5 which is for eosinophils and plasma cell maturation.
And IL-10 that inhibits TH1 phenotype.
what is the second activation factor for CD8 cells?
First is MHC1 interaction.
Second is IL-2 from CD4 TH1 cells.
then they are good to go NAVY SEAL.
What do all naive B cells have?
All have IgM and IgD
How do T helper clls interact with B cells?
T helper cells bind B cells via CD40 receptor binding the CD40L on the T helper cell.
In addition, the T helper cell secretes IL-4 and IL-5 to mediate B-cell isotype switching and plasma cell maturation.
what makes sure that granulomas around TB remain intact?
IFN-gamma from TH1 cells.
Converts macrophages to epitheliod histiocytes and giant cells that wall off the infection.
What is Digeorge syndrome?
Developmental failure of the third and fourth pharyngeal pouches.
22q11 microdeletion presenting with lack of thymus, hypocalcemia, and abnormalities of the heart, great vessels, and face.
What is Severe combined immunodeficiency?
SCID
Defective cell mediated and humoral deficiency.
Cytokine receptor defects
Adenosine deaminase deficiency
MHC II deficiency
Need to bubble baby this person and use stem cell transplant.
What is X-linked agamma globulinemia?
complete lack of immunoglobulin due to error in B-cell maturation.
Mutated tyrosine kinase.
What happens if there is an IgA deficiency?
Most common immunoglobulin deficiency.
Results in increased risk for mucosal infections especially viral.
What is Wiskott Aldrich syndrome?
Thrombocytopenia, eczema and recurrent infections do to a MUTATION IN THE WASP GENE X-LINKED.
Defective humoral and cellular immunity.
If one were deficient in C5-C9 compliment what are they at increase risk for infection of?
Neisseria infections!
what is seen when there is a C1 inhibitor deficiency?
Hereditary angiodema.
Beware of ACE inhibtors in these patients as edema of lips and skin can occur.
What is T cell negative selection.
The removal of self reactive T cells. Occurs in the thymus or bone marrow or become anergic.
What is Libman Sacks endocarditis?
Classic finding in lupus patients.
Small sterile deposits on both sides of the mitral valve.
What are lupus patients have mutation in?
Characteried by antinuclear antibody ANA (sensitive but not specific) and anti dsDNA antibodies (highly specific)
Which three drugs are common agents of drug induced lupus?
Hydralazine
Procainamide (Class 1A)
Isoniazid (RIPE therapy)
Cause lupus through antihistone antibodies.
What is Sjorgren syndrome?
Autoimmune destruction of the lacrimal and salivary glands. Characterized by ANA antibodies.
Type IV mediated (lymphocye mediated Delayed response)
Look for dry eyes (keratoconjuctivitis), dry mouth (xerostomia) and recurrent dental carries in older women.
Which lymphoma are Sjorgren syndrome patients at risk for?
B cell lymphoma.
What is scleroderma?
Autoimmune tissue damage with activation of fibroblasts and deposition of collagen.
Can be difuse or localized and almost any organ can be involved although the esophagus is most common.
Characterized by ANA and anti-DNA topoisomerase (Scl-70) antibody.
Prototype for localized is CREST syndrome with calcinosis, anti centromere antibodis, raynauds, esophageal dysmotility etc.
Describe the difference between labile, stable and permanent tissues.
Labile tissues possess stem cells and can reheal readily. (Small and large bowel, skin, bone marrow)
Stable tissue are quiescent tissues that can regenerate when needed (ex: Liver regeneration after hemisection)
Permanent tissue cannot regernate (myocardium, skeletal muscle, and neurons)
Which type of collagen is immediately layed down following an injury?
Type III collagen.
Later replaced with the high tensile strength type I collagent.
in order to remove type III collagen zinc is required as a cofactor.
What is the major mediator of tissue regeneration and repair?
TGI-alpha which is an epithelial and fibroblast growth factor.
what is primary and secondary intention healing?
Primary is when the wound edges are brought together via suturing.
Secondary intention involves the edges not being approximated. Granulation tissue fills the defect and myofibroblasts contract the wound forming a scar.
Why is vitamin C essential in scar formation?
It is needed to hydroxylate proline and lysin procollagen residues to allow for collagen cross linking.
Copper plays a role in cross linking as well.
Collegenase requires zinc to remove type III collagen after Type I tensile is layed down.
what collagen type is in excess during keloid formation?
Type III collagen excess.
Most common cause of cancer mortality in adults
Lung
Prostate/breast
Colorectal
what are the high risk HPV strains?
16,18,31,33
How does non ionizing radiation cause cell problems?
Sun rays
results in pyridine dimers in DNA normally excised from restriction endonuclease.
Describe the function of Ras
When bound to GTP it sends growth signals to the nucleus.
It normally inactivates itself.
Thus if its constantly on = increased growth factors.
What is the purpose of cyclins?
Cyclins and cyclin dependent kinases form a complex which phosphorylates proteins that drive the cell through the cell cycle.
what are the two tumor supression genes?
P53 and Rb (retinoblastoma) act to supress the risk of tumor supression.
Which stage of the cell cycle does p53 regulate?
Stops G1 from entering the S phase.
If there is DNA damage p53 stops the cells cycle and upregulates repair enzymes.
If it cannot be repaired p53 will induce apoptosis through the BAX pathway
C-myc mutation
Burkitt lymphoma
N-myc mutation
Neuroblastoma
L-myc mutation
Lung carcinoma
Transcription factor.
Describe how p53 can cause apoptosis.
p53 will upregulate the BAX
BAX disrupts Bcl12 allowing protein C to leak out of the mitochondria
What cell cycle stage is regulated by Rb
G1 to S phase by holding onto E2F transcription factor.
When its phosphorylated by cyclin D/ Cyclin dependent kinase 4 it will release E2F allowin cell cycle progression.
Which type of lymphoma is Bcl2 overexpressd?
Follicular lymphoma.
Thus bcl2 cannot be released from the mitochondria inhibiting the release of cytochrome c apoptosis factor.
What role does telomerase play in cell cancers?
Telomerase is generally upregulated preservin the telomeres.
FGF and VEGF are upregulated as well allowing for angiogenesis.
What occurs when E-Cadherins are down regulated in cancer?
These normally keep cells conjoined adjacently.
when down regulated metastasis can occur.
What type of collagen holds cells down to the baement membrane?
Type 4
What is lematrogenous cancer spread?
Common to sarcomas.
Invades the blood supply.
Which carcinoma is characterized by seeding of body cavities?
Ovarian.
Makes sense as it involves the peritoneum.
what is the most important prognostic marker for cancer patients?
Staging is key. Far more important than grading. T - Tumor size/depth N - Tumor spread M - Metastasis (important)
What is the difference between primary and secondary hemostasis?
Primary forms a platelet plug between the platelets and the vascular wall.
Secondary hemostasis stabilizes the platelet plug and is mediated by the hemostasis cascade.
Describe the steps of primary hemostasis.
Transient vasoconstriction via endothelin.
Platelets hook onto vWF sing GP1b.
Platelets release ADP promoting GPIIb/IIa binding and thromboxane via COX is released promoting aggregation and the primary plug.
what are the most common clinical signs of primary hemostasis disorders?
Mucosal and skin bleeding.
Look for petechiae and echymoses as well as purpura.
What are normal platelet ammounts?
150,000-400,000
<50,000 leads to symptoms.
What is immune thrombocytopenic purpura?
Autoimmune production of IgG against platelet antigens GPIIb/IIIa.
Most common form of thrombocytopenia in adults and children.
what is microangiopathic hemolytic anemia?
RBC are sheared as they cross microthrombi from platelets resulting in anemia with schistocytes.
What is Bernard Soulier syndrome?
Degect in GPfb thus platelet adhesion is impaired.
Look for a blood smear with thrombocytopenia and enlarged platelets.
Describe what would happen if there was a deficiency in GPIIB/GPIIIa
Platelet aggregation would be impaired.
How do NSAIDS disrupt platelet aggregation.
Inhibit the formation of thromboxane from COX.
What factor is required for the extrinsic clotting pathway vs the intrinsic?
Extrinsic requires factor 12
Intrinsic requires factor 7
What does PT measure?
Factor 7 and common factors
2,5, 10, and fibrinogen.
What does PTT measure?
Measures intrinsic factors
12,11,9,8
and common factors 1, 5, 10 and fibringen.
What is hemophilia A?
Genetic factor 8 deficiency.
It is X linked recessive mostly in males.
Look for deep tissue joint and post surgical bleeding.
How would PT and PTT be effected in someone with hemophilia A?
This is lack of Factor 8 clotting
Thus the extrinsic PTT would be prolonged with a normal PT.
What is seen in Von Willebrand disease?
Genetic vWF deficiency.
Most common inherited coagulation disorder
Impaired platelet binding, mild mucosal and skin bleeding.
Increase PTT bleeding time and a normal PT.
Keep in mind that VWF carries factor 8.
What is the treatment for von willebrand disease?
Desmopressin (ADH analog) which increases vWF release from Weibel palade bodies of the endothelial cells.
Which factors require vitamin K?
Factors 2, 7, 9, and 10 as well as proteins C and S.
Very common in newbords due to a lack of GI colonization by bacteria that normally synthesize vitamin K. Thus prophylatic vitamin K injections are norm.
