They also have a video lecture on pathology and this guide is called Petomoma. Do you know if they make any plugins to safeguard against hackers? Any suggestions? Your email address will not be published. Save my name, email, and website in this browser for the next time I comment. Notify me of follow-up comments by email. Only o n e isoform is present in neoplasia, which is monoclonal. Clonality can also be determined by androgen receptor isoforms, which are also present on the X chromosome.
Clonality of B lymphocytes is determined by immunoglobulin Ig light chain phenotype. Each B cell expresses light chain that is either kappa or lambda. Normal kappa to lambda light chain ratio is Neoplastic t u m o r s arc benign or malignant. Benign t u m o r s remain localized and do not metastasize.
Malignant t u m o r s cancer invade locally and have the potential to metastasize. T u m o r nomenclature is based on lineage of differentiation type of tissue produced and whether the t u m o r is benign or malignant Table 3.
Table 3. C a n t e r is the 2nd leading cause of death in both adults and children. The leading causes of death in adults are 1 cardiovascular disease, 2 cancer, and 3 cerebrovascular disease. Cancer begins as a single mutated cell. Approximately 30 divisions occur before the earliest clinical symptoms arise. Each division doubling time results in increased mutations. Cancers that do not produce symptoms until late in disease will have undergone additional divisions and, hence, additional mutations.
Cancers that are detected late tend to have a poor prognosis. Goal of screening is to catch dysplasia precancerous change before it becomes carcinoma or carcinoma before clinical symptoms arise. Pap smear—detects cervical dysplasia GIN before it becomes carcinoma 2.
Mammography—detects in situ breast cancer e. Prostate specific antigen PSA and digital rectal exam—detects prostate carcinoma before it spreads 4. Cancer formation is initiated by damage to DNA of stem cells.
The damage overcomes DNA repair mechanisms, but is not lethal. Carcinogens are agents that damage DNA, increasing the risk for cancer. I m p o r t a n t carcinogens include chemicals, oncogenic viruses, and radial ion Table 3.
DNA mutations eventually disrupt key regulatory systems, allowing for t u m o r promotion growth and progression spread. Disrupted systems include pro to-oncogenes, t u m o r suppressor genes, and regulators of apoptosis. P roto -oncoge n e s a re essential to r eel I g rowt h a nd d i ffere n t i at ion; m uta l io n s of proto-oncogenes form oncogenes that lead to unregulated cellular growth.
Categories of oncogenes include growth factors, growth factor receptors, signal transducers, nuclear regulators, and cell cycle regulators Table 3. Growth factors induce cellular growth e. G r o w t h factor receptors mediate signals f r o m growth factors e. Ras is associated with growth factor receptors in an inactive GDP-bound state.
Principles of Neoplasia 25 Table 3. Most common carcinogen worldwide; Carcinoma of oropharynx, esophagus, lung, Cigarette smoke polycyclic hydrocarbons are particularly kidney, and bladder carcinogenic. Activated ras sends growth signals to the nucleus. Mutated ras inhibits the activity of GTPase activating protein. This prolongs the activated state of ras, resulting in increased growth signals.
Cyclins and cyclin-dependent kinases CDKs form a complex which phosphorylates proteins that drive the cell through the cell cycle. Regulate cell growth and, hence, decrease "suppress" the risk of t u m o r formation; p53 and Rb retinoblastoma are classic examples.
K, p53 regulates progression of the cell cycle from G t to S phase, 1. If DNA repair is not possible, p53 induces apoptosis. C y t o c h r o m e c leaks f r o m the mitochondria activating apoptosis, 3. Both copies of the p53 gene must be knocked out for t u m o r formation Knudson two-hit hypothesis. G e r m l i n e mutation results in Li-Fraumeni s y n d r o m e 2nd hit is somatic , characterized by the propensity to develop multiple types of c a r c i n o m a s and sarcomas, C, Rb also regulates progression f r o m G, to S phase.
Rb "holds" the E2F transcription factor, which is necessary for transition to the S phase. Rb mutation results in const it utively free E2F, allowing progression t h r o u g h the cell cycle and uncontrolled g r o w t h of cells. Both copies of Rb gene must be knocked out for t u m o r formation K n u d s o n two- hit hypothesis. Sporadic mutation both hits are somatic is characterized by unilateral retinoblastoma Fig.
Prevent apoptosis in normal cells, but promote apoptosis in mutated cells whose DNA c a n n o t be repaired e. Bcl2 normally stabilizes the mitochondrial m e m b r a n e , blocking release of c y t o c h r o m e c. Bcl2 is overexpressed in follicular l y m p h o m a ,.
Mitochondrial m e m b r a n e is f u r t h e r stabilized, prohibiting apoptosis. Telomerase is necessary for cell immortality. Courtesy of Jerome Fig. J-2 Carcinoma involving lymph node. Normally, telomeres shorten with serial cell divisions, eventually resulting in cellular senescence. Cancers often have up regulated lelomerase, which preserves telomeres. Angiogenesis production of new blood vessels is necessary for t u m o r survival and growth. Avoiding immune surveillance is necessary for tumor survival, 1.
Mutations often result in production of abnormal proteins, which are expressed on MHC. CD8" T cells detect and destroy such mutated cells. Tumor cells can evade immune surveillance by downregyiating expression of MHC class 1. Immunodeficiency both p r i m a r y and secondary increases risk lor cancer. Epithelial t u m o r cells are normally attached to one another by cellular adhesion molecules e. Downregulalion of E-cadherin leads to dissociation of attached ceils. Cells attach to laminin and destroy basement membrane collagen type IV via collagen a se.
Cells attach to fibronectin in the extracellular matrix and spread locally, 5. Entrance into vascular or lymphatic spaces allows for metastasis distant spread.
Lymphatic spread is characteristic of carcinomas, 1. Initial spread is to regional d r a i n i n g lymph nodes Fig. I lematogenous spread is characteristic of sarcomas and some carcinomas. Renal cell carcinoma often invades renal vein 2. Hepatocellular carcinoma often invades hepatic vein 3. Follicular carcinoma of the thyroid 4.
Choriocarcinoma C. Seeding of body cavities is characteristic of ovarian carcinoma, which often involves the peritoneum 'omental caking', Fig, 3. We 11 diff eren i i ated, f oil ic ula r ade noma of thyroid.
Benign t u m o r s tend to be slow g r o w i n g , well circumscribed, distinct, and mobile. Malignant t u m o r s are usually rapid growing, poorly circumscribed, infiltrative, and fixed to s u r r o u n d i n g tissues and local structures. Biopsy or excision is generally required before a t u m o r can be classified as benign or m a l i g n a n t with certainty. Some benign t u m o r s can grow in a malignant-like fashion, and some malignant t u m o r s can grow in a benign-like fashion.
Benign t u m o r s are usually well differentiated Fig. Characteristics include 1. Organized growth 2. Uniform nuclei 3. Low nuclear to cytoplasmic ratio 4. M i n i m a l mitotic activity 5. Lack of invasion of basement m e m b r a n e or local tissue 6. No metastatic potential B. Malignant t u m o r s are classically poorly differentiated anaplastic. Disorganized growth loss of polarity 2.
Nuclear p l e o m o r p h i s m and hyperchromasia 3. High nuclear to cytoplasmic ratio 4. High mitotic activity with atypical mitosis 5. Invasion through basement m e m b r a n e or into local tissue C. Metastatic potential is the h a l l m a r k of malignancy—benign t u m o r s never metastasize. Proteins released by t u m o r into s e r u m e. Useful for screening, monitoring response to treatment, and m o n i t o r i n g recurrence C.
Elevated levels require tissue biopsy for diagnosis of carcinoma e. Microscopic assessment of differentiation i. Well differentiated low grade —resembles normal parent tissue 2.
Poorly d i ffere n t iat ed high g rad e —does no t resem ble pa rent t i s su e B. I m p o r t a n t for d e t e r m i n i n g prognosis; well-differentiated cancers have better prognosis t h a n poorly-differentiated cancers.
Assessment of size a n d spread of a cancer B. Key prognostic factor; more i m p o r t a n t t h a n grade C. Determined after final surgical resection of the t u m o r D. Utilizes T N M staging system 1. N—spread to regional lymph nodes; second most important prognostic factor 3.
Integrity of the blood vessel is necessary to carry blood to tissues. Damage to the wall is repaired by hemostasis, which involves formation of a thrombus clot at the site of vessel injury. Hemostasis occurs in two stages: primary and secondary. Secondary hemostasis stabilizes the platelet plug and is mediated by the coagulation cascade. Step 1—Transient vasoconstriction of damaged vessel 1. Mediated by reflex neural stimulation and endothelin release from endothelial cells B.
Step 2—Platelet adhesion to the surface of disrupted vessel 1. Von Willebrand factor vWF binds exposed subendothelial collagen, 2. Platelets bind vWF using the GPlb receptor. Step 3—Platelet degranulation l. Adhesion induces shape change in platelets and degranulation with release of multiple mediators. Step 4—Platelet aggregation 1. Platelet plug is weak; coagulation cascade secondary hemostasis stabilizes it. Usually due to abnormalities in platelets; divided into quantitative or qualitative disorders B.
Clinical features include mucosal and skin bleeding. Symptoms of mucosal bleeding include epistaxis most common overall symptom , hemoptysis, Gf bleeding, hematuria, and menorrhagia.
Intracranial bleeding occurs with severe thrombocytopenia. Symptoms of skin bleeding include petechiae m m. Useful laboratory studies include 1. Bleeding t i m e — n o r m a l 2 - 7 minutes; prolonged with quantitative and qualitative platelet disorders 3.
Blood smear—used to assess n u m b e r and size of platelets 4. Bone marrow biopsy—used to assess megakaryocytes, which produce platelets III. Most c o m m o n cause of thrombocytopenia in children and adults B, Autoantibodies are produced by plasma cells in the spleen. C, Antibody-bound platelets are consumed by splenic macrophages, resulting in thrombocytopenia.
D, Divided into acute and chronic forms 1, Acute form arises in children weeks after a viral infection or i m m u n i z a t i o n ; s e l f - limited, usually resolving within weeks of presentation 2.
Chronic tbrm arises in adults, usually women of chitdbearing age. May cause short-lived t h r o m b o c y t o p e n i a in offspring since antiplatelet IgG can cross the placenta.
T megakaryocytes on bone m a r r o w biopsy F, Initial treatment is corticosteroids. Children respond well; adults may show early response, but often relapse. IV[G is used to raise the platelet count in symptomatic bleeding, but its effect is short-lived, 2. Splenectomy eliminates the p r i m a r y source of antibody and the site of platelet destruction performed in refractory cases. Platelets are consumed in the formation of microthrombi.
RBCs are "sheared" as they cross microthrombi, resulting in hemolytic anemia with schistocytes Fig. Hemostasls and Related Disorders 33 1. Large, uncleaved multimers lead to abnormal platelet adhesion, resulting in m icrothrombi.
HUS is due to endothelial damage by drugs or infection. L Classically seen in children with E coli G;H7 dysentery, which results from exposure to undercooked beef 2. E coti verotoxin damages endothelial cells resulting in platelet microthrombi. Microangiopathic hemolytic anemia 3. Fever 4. Renal insufficiency more common in HUS —'Fhrombi involve vessels of the kidney. Laboratory findings include 1. Thrombocytopenia with t bleeding time 2. Anemia with schistocytes 4.
Treatment involves plasmapheresis and corticosteroids, particularly in TTP. Bernard-Soulier syndrome is due to a genetic GPfb deficiency; platelet adhesion is impaired. Aspirin irreversibly inactivates cyclooxygenase; lack of TXA, impairs aggregation. Uremia disrupts platelet function; both adhesion and aggregation are impaired. Coagulation cascade generates thrombin, which converts fibrinogen in the platelet plug to fibrin.
Fibrin is then cross-linked, yielding a stable platelet-fibrin thrombus. Factors of the coagulation cascade are produced by the liver in an inactive state. Activation requires 1. Exposure to an activating substance i. Tissue thromboplastin activates factor VII extrinsic pathway. Subendothelial collagen activates factor XII intrinsic pathway. Phospholipid surface of platelets 3. Calcium derived from platelet dense granules II.
Usually due to factor abnormalities B. Clinical features include deep tissue bleeding into muscles and joints hemarthrosis and rebleeding after surgical procedures e.
X-linked recessive predominantly affects males 2. C a n arise f r o m a new mutation de novo without any family history B. Presents with deep tissue, joint, and postsurgical bleeding 1. Clinical severity depends on the degree of deficiency.
N o r m a l platelet c o u n t and bleeding time D. Genetic factor IX deficiency 1. Acquired antibody against a coagulation factor resulting in impaired factor f u n c t i o n ; anfi-FVIII is most c o m m o n , t. Clinical and lab findings are similar to hemophilia A. P T T does not correct u p o n m i x i n g normal plasma with patient's plasma mixing study due to inhibitor; P T T does correct in hemophilia A.
Genetic v W F deficiency 1. Most c o m m o n inherited coagulation disorder B. Multiple subtypes exist, causing quantftfttive a n d qualitative defects; t h e most c o m m o n type is autosomal d o m i n a n t with decreased v W F levels. Presents with mild mucosal and skin bleeding; low v W F impairs platelet adhesion.
T bleeding time 2. Disrupts function of multiple coagulation factors 1, Vitamin K is activated by epoxide reductase in the liver. Deficiency occurs in 1. N e w b o r n s — d u e to lack of GI colonization by bacteria that normally synthesize vitamin K. Hemostasls and Related Disorders 33 2. Long-term antibiotic therapy—disrupts v i t a m i n K-producing bacteria in the GI tract 3. Malabsorption—leads to deficiency of fat-soluble vitamins, including vitamin K Vill. Fragments of destroyed platelets may activate r e m a i n i n g platelets, leading to thrombosis.
Pathologic activation of the coagulation cascade 1. Widespread m i c r o t h r o m b i result in ischemia and infarction, 2. C o n s u m p t i o n of platelets and factors results in bleeding, especially f r o m IV sites and mucosal surfaces bleeding f r o m body orifices.
Almost always secondary to a n o t h e r disease process 1. Obstetric complications—Tissue t h r o m b o p l a s t i n in the amniotic fluid activates coagulation. Sepsis especially w i t h F, Colt or N ttitningitidis —Endotoxins f r o m the bacterial wall and cytokines e. Acute promyelocytic l e u k e m i a — P r i m a r y granules activate coagulation.
Rattlesnake bite—Venom activates coagulation. Laboratory findings include J, I platelet count 2. Microangiopathic hemolytic a n e m i a 5. Derived from splitting of cross-linked fibrin; D - d i m e r is not produced f r o m splitting of fibrinogen. Treatment involves addressing the underlying cause and transfusing blood products and cryoprecipitate comains coagulation factors , as necessary. Plasmin cleaves fibrin and serum fibrinogen, destroys coagulation factors, and blocks platelet aggregation.
Disorders of fibrinolysis are due to plasmin overactivity resulting in excessive cleavage of s e r u m fibrinogen. Presents with increased bleeding resembles D1C D. Increased fibrinogen split products without D - d i m e r s — S e r u m fibrinogen is lysed; however, D - d i m e r s arc not formed because fibrin t h r o m b i are absent.
Treatment is aminocaproic acid, which blocks activation of plasminogen. Pathologic formatiun of an intravascular blood clot thrombus 1. Most c o m m o n location is the deep veins DVT of the leg below the knee. U and 2 attachment to vessel wall I. Three major risk factors for thrombosis are disruption in blood low, endothelial cell damage, and hypercoagulablestate Virchow triad.
Blood llow is normally continuous and laminar; keeps platelets and factors dispersed and inactivated B. Immobilization—increased risk for deep venous t h r o m b o s i s 2. Cardiac wall dysfunction e. Aneurysm III. Endothelial damage d i s r u p t s the protective function of endothelial cells, increasing the risk for thrombosis. Endothelial cells prevent thrombosis by several mechanisms.
Block exposure to subendothelial collagen and underlying tissue factor 2. Causes of endothelial cell d a m a g e include atherosclerosis, vasculitis, and high levels of homocysteine. V i t a m i n B12 and folate deficiency result in mildly elevated homocysteine levels, increasing the risk for thrombosis.
C o b a l a m i n transfers methyl to homocysteine resulting in methionine, iv. Cystathionine beta synthase CBS deficiency results in high homocysteine levels with homocystinuria, i. CBS converts homocysteine to cystathionine; e n z y m e deficiency leads to h o m o c y s t e i n e buildup. Characterized by vessel thrombosis, mental retardation, lens dislocation, and long slender fingers.
Due to excessive procoagulant proteins or defective anticoagulant proteins; may be inherited or acquired B. Usually occurs in the deep veins of the leg; o t h e r sites include hepatic and cerebral veins.
Protein C or S deficiency autosomal d o m i n a n t decreases negative feedback on the coagulation cascade. Increased risk for w a r f a r i n skin necrosis i. In preexisting C or S deficiency, a severe deficiency is seen at the onset of warfarin therapy increasing risk for thrombosis, especially in the skin.
Factor V Leiden is a m u t a t e d form of factor V that lacks the cleavage site for deactivation by proteins C and S. Most c o m m o n inherited cause of hypercoagulable state E. P r o t h r o m b i n A is an inherited point mutation in p r o t h r o m b i n that results in increased gene expression, I.
ATIII deficiency decreases the protective effect of heparin-I ike molecules p r o d u c e d by the endothelium, increasing the risk for t h r o m b u s. High doses of h e p a r i n activate limited ATIII; Coumadin is t h e n given to m a i n t a i n an anlicoagulated state. Oral contraceptives are associated with a hypercoagulable state.
Intravascular mass that travels and occludes d o w n s t r e a m vessels; symptoms depend on the vessel involved. Atherosclerotic embolus is d u e to an atherosclerotic plaque that dislodges. Characterized by the presence of cholesterol clefts in the embolus Fig. Far embolus is associated with bone fractures, particularly long bones, and soft tissue t r a u m a.
Develops while f r a c t u r e is still present or shortly after repair 2. Characterized by dyspnea fat, often with b o n e m a r r o w elements, is seen to p u l m o n a r y vessels, Fig. Gas embolus is classically seen in decompression sickness. Nitrogen gas precipitates out pf blood due torapid ascent by a diver. Presents with joint and muscle pain 'bends' and respiratory symptoms 'chokes'. Chronic form Caisson disease is characterized by multifocal ischemic necrosis of bone. Gas embolus may also o c c u r d u r i n g laparoscopic surgery air is p u m p e d into the abdomen , F.
Amniotic fluid embolus enters maternal circulation d u r i n g labor or delivery!. Presents with shortness of breath, neurologic symptoms, and DIC due to the thrombogenic nature of amniotic fluid 2. Characterized by s q u a m o u s cells and keratin debris, f r o m fetal skin, in embolus Fig.
Usually d u e to t h r o m b o e m b o l u s ; the most c o m m o n source is deep venous t h r o m b u s DVT of the lower extremity, usually involving the femoral, iliac, or popliteal veins. Most often clinically silent because 1 the lung has a dual blood supply via p u l m o n a r y and bronchial arteries and 2 the embolus is usually small self- resolves C. B Fat embolus with bone marrow elements. Web icon An illustration of a computer application window Wayback Machine Texts icon An illustration of an open book.
Books Video icon An illustration of two cells of a film strip. Video Audio icon An illustration of an audio speaker. Audio Software icon An illustration of a 3. Software Images icon An illustration of two photographs. In this part of the article, you will be able to access the Fundamentals of Pathology Pathoma PDF using our direct download links.
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