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245 Cards in this Set

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Antithrombogenic substances
Prostacyclin (PGI2), nitric oxide, tissue plasminogen activator, thrombomodulin
Steps in hemostasis
1. Endothelial injury relases tissue factor (activates factor VII, extrinsic pathway); exposure of thrombogenic subendothelial collagen activates factor XII (intrinsic pathway), release of vWF; decreased synthesis of antithrombogenic substances; 2. Platelet adhesion to vWF through glycoprotein Ib; 3. Platelet activation with degranulation and synhesis of TXA2 and ADP (aggregators); 4. Aggregation mediated by TXA2 and ADP and fibrinogen/Gp IIb-IIIa
Bernard Soulier syndrome
Autosomal recessive. Deficiency of platelet GPIb. Defective platelet adhesion
Glanzman thrombastenia
Deficiency of Gp IIB-IIIa; defective platelet aggregation
Immune thrombocytopenic pupura
Antiplatelet antibodies and destruction in spleen by macrophages (bind IgG coated platelets via Fc receptor). Thrombocytopenia, prolonged bleeding time, normal PT and PTT. Petechiae, ecchymoses, menorrhagia, nosebleeds. Present in Wiskot-Aldrich
Thrombotic thrombocytopenic purpura
Platelet thrombi with scant fibrin with no activation of coagulation system. Fever, thrombocytopenia, hemolytic anemia, neurologic symptoms, renal failure. Increased bleeding time, normal PT/PTT, schistocytes
Hemolytic uremic syndrome
Gastroenteritis with bloody diarrhea, fever, thrombocytopenia, renal failure, hemolytic anemia. Produced by verotixin-producing E. coli 0157
Activation of coagulation system
Intrinsic pathway (Factor XII): exposure to subendothelial collagen; Extrinsic pathway (factor VII): tissue thromboplastin by endothelium
Kinin cascade
Hageman factor converts prekallikrein into kallikrein. HMWK is converted to bradykinin by kallikrein
Fibrinolytic system cascade
Kallikrein activates plasminogen into plasmin which inhibits fibrin from coagulation cascade
Vitamin K-dependant factors
Factors II, VII, IX, X. Both intrinsic and extrinsic paths need vitamin k-dependant gamma carboxylation
Prothrombin time (PT)
Tests extrinsic and common paths. Factors V, VII, X, prothrombin and fibrinogen. Used to monitor warfarin therapy
MOA of warfarin
Blocks epoxide reductase (activates vitamin K). Takes 3-4 days for effect due to long half life of previously carboxylated factors which are still circulating
Partial thromboplastin time (PTT)
Tests intrinsic and common paths. Factors XII, XI, IX, VIII, X, V, prothrombin, fibrinogen. Used to monitor heparin
DIC
Thrombocytopenia, prolonged PT/PTT, decreased fibrinogen, elevated D-dimers
Hemophilia
Deficiency of factor VIII or IX. X-linked recessive (affects males). Bleeding at circumcision, hemarthrosis, easy bruising and hematomas. No petechiae or ecchymoses. Normal platelets and bleeding time, normal PT, prolonged PTT (intrinsic path coagulopathy)
Increased PT and PTT
Vitamin K deficiency, liver disease
Von Willenbrand disease
bleeding from mucuous membranes, prolonged bleeding time, normal PT/PTT, abnormal response to ristocetin
Auto mechanics
Carbon monoxide poisoning. Decreased SaO2, cherry red color of skin, headache. Rx.: 100% O2
Firefighters
Carbon monoxide poisoning. Decreased SaO2, cherry red color of skin, headache. Rx.: 100% O2
Wood stoves and space heaters
Carbon monoxide poisoning. Decreased SaO2, cherry red color of skin, headache. Rx.: 100% O2
Pesticide industry
Organophosphate poisoning (acetylcholinesterase inhibitors) and arsenic. Lacrimation, salivation, miosis, weakness. Rx.: atropine
Meat packing industry
Plyvinyl chloride (PVC). Hepatic angiosarcoma
Coal workers
Anthracosis. Pulmonary fibrosis and respiratory distress
Insulation workers
Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain
Demolition workers
Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain
Construction workers
Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain
Shipyard workers
Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain
Dry cleaners
Carbon tetrachloride (CCL4). Liver centrilobular necrosis
Rubber/chemical workers
Benzene. Aplastic anemia, leukemia
Battery factory workers
Lead poisoning. MOA: denatures ferrochelatase, (microcytic anemia with ringed sideroblasts), denatures ALA dehydrase. Clinical features: depositis in epiphysis, lethargy, cognitive impairment, cerebral edema, lead colic, basophilic stipling. Dx.: blood lead levels
Plumbers
Lead poisoning. MOA: denatures ferrochelatase, (microcytic anemia with ringed sideroblasts), denatures ALA dehydrase. Clinical features: depositis in epiphysis, lethargy, cognitive impairment, cerebral edema, lead colic, basophilic stipling. Dx.: blood le
Pottery paint
Lead poisoning. MOA: denatures ferrochelatase, (microcytic anemia with ringed sideroblasts), denatures ALA dehydrase. Clinical features: depositis in epiphysis, lethargy, cognitive impairment, cerebral edema, lead colic, basophilic stipling. Dx.: blood le
Combustion of polyurethane foam during fires
Cyanide poisoning. Blocks cytochrome oxidase. Hypoxia. Rx.: nitrites (form methhemoglobin which binds cyanide before it reaches tissues), thiosulfate bind cyanide forming thiocyanate
Dental amalgams
Mercury poisoning. Intention tremors, dementia, delirium
Insecticides
Mercury poisoning. Intention tremors, dementia, delirium
Hat-making industry
Mercury poisoning. Intention tremors, dementia, delirium
Cancers produced by cigarette smoke
Lung, oral cavitiy, pharynx, larynx, esophagus, pancreas, kidney
Cardiovascular disease due to cigarette smoke
Atherosclerosis (major risk factor), CAD, AMI, Buerger disease
Respiratory disease due to cigarette smoke
Chronic bronchitis, emphysema, asthma
Diseases associated with alcohol
Thiamine deficiency (Wernicke-Korsakoff), macrocytic anemia (folate deficiency), Mallory-Wiess, Boerhaave's syndrome, cirrhosis, esophageal varices, acute pancreatitis, congestive cardiomyopathy, hyperlipidemia
Down syndrome
Trisomy 21 due to meiotic nondisjunction (95%) or robertsonian translocation (4%); Severe mental retardation, mongoloid features, brushfeld spots, simian crease, heart defects, duodenal atresia, Hirchsprung, ALL, Alzheimer's by age 40
Edward syndrome
Trisomy 18. Mental retardation, low set ears, micrognathia, heart defects, overlapping flexed fingers, rocker-bottom feet
Patau syndrome
Trisomy 13. Mental retardation, cleft lip or palate, cardiac defects, renal defects, microcephaly, polydactyly
Cri du chat
5p deletion. Cat-like cry, mental retardation, heart defects, microcephaly
Klinefelter syndrome
47XXY. Male hypogonadism, testicular atrophy, infertility, female distribution of hair, gynecomastia, elevated LH/FSH, low levels of testosterone
Turner syndrome
45X0. Female hypogonadism, no barr body, no secondary sex characteristics, short stature, widely spaced niples, gonadal dysgenesis, amenorrhea, infertility, hypothyroidism, preductal coarctation of the aorta, bicuspid aortic valve
Female hermaphrodite
46XX. Female internal organs, virilized external genitalia. Cause: congenital adrenal hyperplasia, androgen-producing tumor
Male hermaphrodite
46XY. Testes present, female genitalia, testicular feminization. Cause: androgen insensitivity syndrome
CCystic Phibrosis
Chloride Channel protein defect, deletion of phe 508 on chromosome 7. Recurrent psudomona/staph infections, chronic bronchitis, bronchiectasis, atrophy of pancreatic ducts, pancreatic insuficiency, fat malabsorbtion, steatorrhea, infertility, meconium ileum, elevated NaCl sweat test
PKU
Deficiency of phenylalanine hydroxylase. Mental retardation by 6 months, light-colored hair and skin, musty odor. Avoid aspartame, monitor pregnancy
Alkaptonuria
"Black Homo" homogentisic acid oxidase deficiency. Black urine, black cartilage
Albinism
Tyrosinase deficiency. Increased risk of squamous carcinoma, no melanin
Von Gierke disease
Glucose 6 phosphatase deficiency. Hepatomegaly, fasting hypoglycemia, hyperuricemia
Pompe disease
Lysosomal alpha 1-4 glucosidase deficiency. Hepatomegaly, muscle hypotonia, cardiomegaly
McArdle disease
Myophosphorylase deficiency. Excersice-induced muscle cramps
Tay SaX
Hexosaminidase A deficiency with acumulation of glangliocerebroside GM2. Mutation of HEXA gene on chromoseme 15. Cherry-red spot on retina
Nieman PickS
Sphingomyelinase deficiency. Cherry-red spot on retina, hepatosplenomegaly, zebra bodie on EM
Gaucher disease
Glucocerebrosidase deficiency. In adulthood, hepatosplnomegaly, hypersplnism, lymphadenopathy
Mucopolysaccharidosis
Glycosaminoglycans acumulation. Mental retardation, cloudy cornea, coarse facial features, hepatosplnomegaly, skeletal deformities
Familial hypercholesterolemia
Mutation on LDL receptor gene on chromosome 19. Xanthomas, xanthelasmas, atherosclerosis, achiles tendon xanthoma
Marfan syndrome
Mutation of fibrillin gene on 15q. Tall, thin with big extremities, hyperextensible joints, pectus excavatum, ectopia lentis, disecting aortic aneurysm, aortic insuficiency, mitral prolapse
Ehlers-Danlos
Hyperxtensible skin and joints. Collagen gene defects
Menkes disease
Mutation in Cu+ efflux protein gene. High concentration of Cu+ that cant be released. Associated with Ehlers-Danlos type 9
Neurofibromatosis type 1
Von Recklinghousen disease (has 17 letters). NF-1 tumor suppressor gene mutation on chromosome 17. Normal gene product neurofibromim inhibits p21 ras oncoprotein. Neurofibromas, café-au-lait spots, Lisch nodules (pigmented iris hamartomas)
Neurofibromatosis type 2
NF-2 tumor suppressor gene mutation on chromosome 22. Bilateral acoustic neuromas, café-au-lait spots, pheochromocytoma
Von Hippel Lindau disease
Mutation on VPL tumor suppressor gene on chromosome 3p. Retinal hemangioblastoma, hemangioblastoma of cerebellum, brainstem and spinal cord, cysts of the liver, pancreas and kidneys, bilateral renal carcinomas
Fragile X syndrome
X-linked dominant mutations on FMR-1 gene. CGG triplet repeats. Retardation elongated face with large jaws, large everted ears, macroorchidism
Huntington disease
CAG triplet repeats of huntington gene produces neurotoxic protein. Progressive dementia, choreiform movements
Prader-Willi syndrome
Deletion of paternal 15q. Mental retardation, obesity, hypogonadism, hypotonia
Angelman syndrome
deletion of maternal 15q. Retardation, seizures, ataxia, inapropriate happy-puppet laughter
Homocystinuria
Cysthathione synthase deficiency. Resembles Marfan. Ectopic lens, arachnodactyly, eunuchoid proportions osteoporosis, atherosclerosis, DVT
Classic 21B-Ohase deficiency
Hypovolemia, hyponatremia, female pseudohermaphrodite, hirsutism (increased 17 KS), skin hyperpigmentation (high ACTH increases melanin). Labs: increased serum 17OH-progesterone, hyperkalemia, metabolic acidosis, increased 17KS, decreased 17OHCS, hypocortisolism
Non-classic 21B-Ohase deficiency
Increase in 17 KS, hirsutism, no salt loss, acne in females, secondary amenorrhea. Labs: increased 17OH pregenterone
Classic 11OHase deficiency
Salt retention/hypertension (11-deoxycorticosterone), increased 17KS (virilization), skin hyperpigmentation
17OHase deficiency
Salt retention, hypertension, (aldosterone), female hypogonadism (decreased 17KS), male pseudohermaphrodite (low 17KS). Labs: low 17KS, 17OHCS, hypocortisolism, increased ACTH
Clinical features of SLE
Type II and III hypersensitivity reactions. Pancytopenia, arthritis, butterfly rash, diffuse proliferative glomerulonephritis, Libman-Sacks endocarditis. ANA, anti-DNA, anti-Sm, anti-histone (drug-induced lupus). Rx.: steroids
Sjogren syndrome
Autoantibodies against lacrimal and salivary glands. Keratoconjunctivitis, corneal ulcers (dry eyes), xerostomia (dry mouth). Anti-Ro (SS-A), anti-La (SS-B). 15% of rheumatoid arthritis patients have Sjogren.
Mikulicz syndrome
Enlargement of the salivary and lacrimal glands associated with Sjogren syndrome
Diffuse scleroderma
Fibroblast stimulation and deposition of collagen in the skin and internal organs. Anti-DNA topoisomarease I (Scl-70) (helicase). Skin involvement, dysphagia, malabsorption, pulmonary fibrosis (dyspnea), cardiac fibrosis (arrhythmias), kidney fibrosis (renal failure)
Localized scleroderma (CREST)
Fibroblast stimulation and deposition of collagen. Anti-centromere antibodies. Calcinosis, Raynaud, esophageal dysmoility, sclerodactyly, telangiectasia.
Bruton's agammaglobulinemia
X-linked recessive. No B cells, No Igs. Recurrent staph, haemophilus and strep infections after 6 months. Increased pre-B cells. Mutation of B-cell Bruton tyrosine kinase (btK).
Common variable immunodeficiency
B-cell maturation defect. Hypogammaglubulinemia, recurrent bacterial infections, giardia lamblia.
DiGeorge syndrome
Failure to develop 3rd and 4th pharyngeal puches results in absence of parathyroid and thymus glands, hypocalcemia, tetany, T-cell deficiency, recurrent viral infections, heart defects, chronic candidiasis
SCID
B and T cell deficiency due to mutation of IL-2 receptor (x-linked), adenosine deaminase deficiency (AR) or failure to make MHC II. Recurrent infections and susceptibility to candida, CMV and p. carinii
Wiskot-Aldrich syndrome
X-linked recessive. "WIPE": recurrent infections, thrombocytopenic purpura, eczema, risk of lymphomas, low IgM
Ataxia-Telangiectasia
Ataxia, spider angiomas, low IgA, defect of DNA repair enzyme
Chronic granulomatous disease
Low NADPH oxidase. Recurrent catalase+ infections, negative nitroblue tetrazolium test.
Leukocyte adhesion deficiency
Defect of CD-18 (LFA-1 beta chain), no pus formation, failure of umbilical cord to detach
Chediak-Higashi
Defect in microtubules with no phagocytosis by lysosome. Partial albinism, peripheral neuropahty, recurrent infections
Hereditary angioedema
Edema at mucosal surfaces. Defect of C1-INH (esterase inhibitor). Decreased C1, C2, C4
Hyper IgM
Defect of CD-40L on T-lymphocytes. No isotope switching, increased IgM
MHC-I deficiency
Normal CD4, no CD8. Failure of TAP-1 to transport peptides to MHC-I groove
Amyloid stains
Stains red with Congo-red stain then apple green birefringence under polarized light
Signs and symptoms of amyloidosis
Nephrotic syndrome, renal failure, arrythmias, CHF, hepatosplenomegaly, macroglosia
Mediators of leukocyte margination
Selectins mediate margination. P and E selctins on endothelium bind Sialyl-Lewis on leukocyte; GlyCAM/CD34 on endothelium binds L-selectin on leukocyte
Mediators of leukocyte adhesion
Integrins mediate adhesion. ICAM, VCAM on endothelium bind LFA-1 and VLA on leukocyte
Regulators of leukocyte margination and adhesion
Histamine upregulates P-selectin. IL-1 and TNF induce E-selectin, ICAM and VCAM. Chemotactic agents cause conformational change of LFA-1
Leukocyte adhesion deficiency
Defect of CD18 (beta chain subunit of LFA-1 integrin on leukocytes). Recurrent infections, no pus formation, failure of umbilical cord to detach
Chemotactic factors
N-formyl methionine, leukotriene B4, C5a, IL-8
Opsonins
Fc portion of IgG, c3b, C reactive protein
Chediak-Higashi syndrome
Defect of microtubule polymerization causes defect in chemotaxis and degranulation. Partial albinism, peripheral neuropathy
CGD
NADPH oxidase deficiency. No production of superoxide for respiratory burst. Recurrent catalase+ infections, negative nitroblue tetrazolium test
Arachidonic acid products
AA producedd by phospholipase A2 (inhibited by steroids). Produces leukotrienes, prostaglandins and thromboxane A2
Lypoxigenase pathway
Arachidonic acid is converted to leukotrienes by 5-lypoxigenase. LTB4 --> chemotaxis. LTC4, D4, E4 --> bronchoconstriction
Cycloxigenase pathway
Arachidonic acid is converted to TXA2 and prostaglandins (NSAIDs block). TXA2 --> vasoconstriction, platelet aggregator. PGI2, PGE2, PGF2
Mediators of vasodilation
Histamine , bradikinin, PGI2, PGD2, E2, F2
Mediators of pain
Bradikinin, PGE2
Mediators of increased permeability
Histamine, Bradikinin
Mediators of vasoconstriction
TXA2, LTC4, D4, E4
Mediators of bronchoconstriction
LTC4, D4, E4, bradikinin
Mediators of fever
IL-1, PGD2, E2, F2
Anaphilotoxins
C3a, C5a. Directly stimulate histamine release from basophils, mast cells and platelets
C3b
Opsonin; neutrophils, macrophages and monocytes have C3b receptros
Bradikinin synthesis and actions
Synthesized from activation of prekalikrein by factor XII (Hageman). Kalikrein cleaves HMWK into bradikinin. Vasodilator, increased permeability, brnchoconstrictor, pain
PGE2
Vasodilation in kidneys, increases renal blood flow, increases gastric mucosal blood flow (mucoprotection), activates osteoclasts, fever, pain, maintains ductus arteriosus
Prostacyclin (PGI2)
Vasodilation and inhibits platelet aggregation
IL-1
Stimulates PGE2 synthesis in hypothalamus --> fever; B-cell stimulation to synthesize Ig; osteoclast activation (released by osteoblasts under PTH stimulation); lytic bone lessions of multiple myeloma; increases adhesion molecules in endothelium; increases acute phase reactants
Hageman factor
Activates intrinsic coagulation system, kinin cascade and fibrinolytic system
PGF
Uterine muscle contraction (cause pf primary amenorrhea)
gamma interferon
Produced by CD4 cells and NK cells. Activates macrophages; antiviral properties; class I and class II antigens; increases IL-2, IL-12 production by CD4 cells
IL-2
Produced by CD4 cells. T cell growth factor. Promotes B cell and NK cell proliferation
IL-6
Synthesis of acute phase reactants
Factors that increase adhesion molecule synthesis
C5a, LTB4, IL-1, TNF
Key cells in acute and chronic inflamation
Acute: neutrophil has IgG and C3b receptros; Chronic: macrophage has receptors for IgG and C3b, process antigen and secrete IL-1, IL-12 and TNF
Chronic granulomatous inflamation
Epitheloid cells and multinucleated giant cells surrounded by a rim of lymphocytes with central caseous necrosis
Type I collagen
skin, bones, tendons and most organs
Type II collagen
Cartilage and vitreous humor
Type III collagen
granulation tissue
Type IV collagen
basement membranes
Composition of basement membranes
Has negative charge. Collagen type IV, proteoglycans (heparan sulfate), laminin, fibronectin
Nitrosamines
Gastric CA, Esophagus
Cigarette smoke
Larynx, ling, renal cell carcinoma, transitional cell carcinoma
Polycyclic aromatic hydrocarbons
Bronchogenic CA
Asbestos
Bronchogenic CA, mesothelioma
Chromium and nickel
Bronchogenic CA
Arsenic
Squamous cell CA of skin and lung, angiosarcoma of liver
Vinyl chloride (PVC)
Liver angiosarcoma
Alkalating agents
Leukemia, lymphoma
Benzene
Leukemia, lymphoma
Napthalene
Bladder CA
CCL4
Liver centrilobular necrosis
HTLV-1
Adult T-cell leukemia
HBV, HCV
Hepatocellular CA
EBV
Burkitt's lymphoma, nasopharyngeal CA
HPV
Cervical CA (16, 18)
HHV-8
Kaposi sarcoma
hst-1 & int-2
Cancer of stomach, breast, bladder and melanoma; produces growth factors; overexpression
sis
Astrocytoma; produces PDGF; overexpression
erb-B1
SCC of lung; produces EGF receptor; overexpression
erb-B2
Breast, ovary and lung CA; produces EGF receptor; amplification
erb-B3
Breast; produces EGF receptor; overexpression
ret
MEN II & III, medullary thyroid CA; produces glial neurotrophic factor receptor; Point mutation
abl
CML, ALL; produces signal transduction proteins; translocation t(9:22), Philadelhpia chromosome
Ki-ras
Lung, pancreas and colon; produces GTP binding proteins; Point mutation
c-myc
Burkitt lymphoma; produces nuclear regulatory protein; translocation t(8:14). When associated to p53 apoptosis; when associated to bcl-2 inhibits apoptosis
L-myc
Small cell lung CA; produces nuclear regulatory protein; amplification
N-myc
Neuroblastoma; produces nuclear regulatory protein; amplification
bcl-1
Mantle cell lymphoma; produces cyclin D protein; translocation t(11:14)
CDK4
Melanoma; produces cdk; amplification
bcl-2
Normally prevents apoptosis. Follicular and undiferentiated lymphomas t(14:18). Chromosome 14: Ig heavy chain; chromosome 18 bcl-2
c-kit
gastrointestinal stromal tumor
p53
Normally prevents a cell with damaged DNA from entering S-phase by inhibiting cyclin/cdk. Colon, breast, CNS, lung. On chromosome 17
Rb
Normally prevents a cell from entering S phase. Retinoblastoma, osteogenic sarcoma. Inactivated product by cyclin/cdk. On chromosome 13
Alpha fetoprotein
Hepatocellular CA, testicular tumors
B-hCG
Trophoblastic tumors, chroriocarcinoma
Calcitonin
Medullary CA of thyroid
CEA
lung, pancreas, stomach, breast, colon
CA-125
Ovarian CA
CA19-9
Pancreatic CA
Placental alkaline phosphatase
Seminoma
Prostatic acid phosphatase
Prostate CA
PSA
Prostate CA
Alkaline phosphatase
Metastasis to bone, primary billiary cirrhosis
VHL
Chr 3p. Von Hippel Lindau, renal cell CA
WT-1, WT-2
11p. Wilm tumor
BRCA-1
17q. Hereditary breast and ovarian CA
BRCA-2
13q. Hereditary breast CA
APC
5q. Adenomatous polyps and colon CA
DCC
18q. Colon CA
NF-1
17q. Neurofibromatosis
NF-2
22q. Acoustic neuromas and meningiomas
Down Syndrome
ALL, AML
Xeroderma pigmentosum, albinism
Squamous cell, basal cell CA, melanoma
Chronic atrophic gastritis, pernicious anemia, H. pylory
Gastric adenocarcinoma
Tuberous sclerosis
Astrocytoma; produces PDGF; overexpression
Actinic keratosis
Squamous cell CA of skin and lung, angiosarcoma of liver
Barret's esophagus
Esophageal adenocarcinoma
Plummer-Vinson syndrome
Iron deficiency causes atrophic glositis, esophageal webs, anemia, squamous cell CA of esophagus
Cirrhosis
Hepatocellular CA
Ulcerative colitis
Colonic adenocarcinoma
Paget's
Osteosarcoma
Immunodeficiency
Malignant lymphomas
AIDS
Non-Hodgikin's, Kaposi
Dysplastic nevus
Malignant melanoma
Radiation
Sarcoma
Small cell lung CA paraneoplastic syndromes
Cushing's (ACTH), SIADH (ADH)
Squamous cell lung CA paraneoplastic syndrome
Hypercalcemia (PTH), TGF-b, TNF, IL-1
Renal cell CA paraneoplastic syndrome
Polycythemia (EPO), hypertension (renin)
Thymoma, Small cell lung CA paraneoplastic syndromes
Lamber-Eaton (antibodies against presynaptic CA channels at neuromuscular junction)
Leukemias and lymphomas paraneoplastic syndromes
Gout (hyperuricemia due to excess nucelic acid turnover)
Acanthosis nicrans
Gastric adenocarcinoma
Carcinoid tumor or medullary thyroid CA paraneoplastic syndromes
Flushing, diarrhea (serotonin)
alpha1-antitrypsin
Hepatocellular CA
Bence Jones protein
Multiple Myeloma (Ig light chains in urine)
MEN-I
Pituitary (ACTH, Cushings), parathyroid (hypercalcemia), pancreas (zollinger-ellison, insulinoma)
MEN-II
medullary thyroid CA, parathyroid adenoma (hypercalcemia), pheocromocytoma (hypertension)
5 leading causes of death in US
1. Heart disease; 2. Cancer; 3. Cerebrovascular disease; 4. COPD; 5. Accidents
3 leading causes of death in children in US
1. Accidents; 2. Cancer; 3. Congenital abnormalities
3 most common cancers in males
1. Prostate; 2. Lung and bronchus; 3. Colon/rectum
3 most common cancers in females
1. Breast; 2. Lung; 3. Colon/rectum
Top 3 cancer mortality in males
1. Lung; 2. Prostate; 3. Colon/rectum
Top 3 cancer mortality in females
1. Lung; 2. Breast; 3. Colon/rectum
5 causes of tissue hypoxia
ischemia, hypoxemia, ETC block, uncoupled ETC, AV shunts
Ultimate effects of tissue hypoxia
No O2 to accept electrons in ETC, no production of ATP. Na/K pump fails and cell swells (reversible change). Ribosomes fall from RER. Disruption of cell membrane and mitochondria induces apoptosis.
Effects of low ATP in cell
Increased glycolysis to support ATPase pump. Anaerobic glycolysis produces lactate with decreased intracellular pH which denatures proteins (coagulation necrosis), cell swelling, entry of calcium and apoptosis
Pathophysiology of cell injury in hypoxia
ETC fails due to lack of oxygen; 2. No ATP production in ETC increases anaerobic glycolysis (high citrate and AMP activate PFK-1); 3. increased lactate decreases cell pH which denatures proteins and produces coagulation necrosis; 4. ATPase fails and cell swells with fall off of ribosomes from RER; 5. disruption of cell membrane with entry of Ca activates phospholipase (lipid peroxidation), complement activation, nuclear enzymes with pyknosis and destruction of mitochondria and apoptosis
What is methhemoglobin?
Hemoglobin with oxidized (Fe3+) iron that cant bind O2. Decreases SaO2 and produces cyanosis. Caused by nitro/sulfa compounds. Rx.: methylene blue
Increased PACO2, decreased PaO2, decreased O2 content, decreased SaO2
Respiratory acidosis
Normal PaO2 and SaO2, decreased Hb
Anemia
Normal Hb, PaO2, decreased SaO2, decreased O2 content
CO poisoning or methhemoglobinemia
CO poisoning tissue hypoxia
Decreased O2 content and SaO2, normal PaO2, left shift of dissociation curve and cytochrome oxidase inhibition all cause hypoxia. Produced by car exhaust, heaters, smoke inhalation, wood stoves. Rx.: 100% O2. First symptom: headache
Factors that left-shift O2 dissociation curve and decrease P50
Decreased 2,3BPG, CO, MetHb, HbF, hypothermia, alkalosis
Factors that right-shift O2 dissociation curve and increase P50
Increased 2,3BPG, fever, acidosis
Causes of hypoxia with normal O2 content
Ischemia, cyanide poisoning, ETC uncouplers (alcohol, salicylates, dinitrophenol)
Free radical metabolism
NADPH oxidase and spontaneous superoxide, Superoxide dismutase makes H2O2 from superoxide. Catalase breaks down H2O2. Gluthathione reductase and GSH peroxide breakdwon H2)2 using reduced GSH and NADPH from G6PDH in HMP shunt
Causes of free radical injury
Aging process produces lipofuscin which peroxidates membrane; MPO system, O2 free radicals, ionizing radiation, acetaminophen (treat with acetylcyteine), CCl4 poisoning
Features of apoptosis
Eosinophilic cytoplasm; pyknotic nucleus, no inflamatory infiltrate
Physiologic examples of apoptosis
Thymus involution, Mullerian and Wolffian structure involution, gravid uterus
Pathologic examples of apoptosis
Councilman bodies in viral hepatitis, psammoma bodies, cancer
Coagulation necrosis
Denaturing and coagulation of proteins in cytoplasm (infarction). Pale Vs. hemorrhagic infarcts
Liquefactive necrosis
Neutrophil destruction with hemolytic enzymes. Abesesses, wet gangrene, brain, pancreas
Caseous necrosis
Combination of coagulation and liquefaction necrosis. Cheese-like material, casseating granulomas with macrophages
Fat necrosis
Lipases on fatty tissue. Pancreas. Chalky-white appearance
Fibrinoid necrosis
Histologically resembles fibrin. Eosinophilic mitral valve vegetations, immunocomplexes
Fatty liver change
In alcoholics - liver stores excess tryglycerides because increased NADH produces glycerol 3P and increased acetate (acetyl CoA) increases FA synthesis. In kwashiorkor, no apolipoproteins for VLDL
Regulation of apoptosis
Genes bcl-2 (inhibits apoptosis) prevents release of cytochrome C and binds protease activating factor (Apaf-1); p53 stimulates apoptosis. Mediated by caspases. Stimulated by cell injury, lack of hormones, Fas and TNF
Rb suppressor gene and Rb protein
Located on chromosome 13. Produces unphosphorylated Rb protein which stops cell from entering S phase. Phosphorylation by cyclin D/cdk complex allows it to enter S phase. Mutation of Rb gene produces cancer
cdk/cyclin D complex
When activated it phosphorylates Rb protein allowing cell to enter S phase
p53 suppressor gene
Located on chromosome 17. Produces a protein that inactivates cyclin D/cdk complex preventing Rb protein phosphorylation which keeps cell in G1
Fibronectin
Binds collagen, fibrin and integrins; adhesion glycoprotein of extracellular matrix; chemotactic for fibroblasts and endothelial cells
VEGF
vascular endothelial growth factor; important in angiogenesis
FGF
Fibroblast growth factor; important in angiogenesis
PDGF
Stimulates granulation tissue formation; stimulates proliferation of smooth muscle, fibroblasts and endothelium
Laminin
Adhesion protein in basement membranes; binds type IV collagen, integrins and ECM components