674 terms

USMLE Pathology

Antithrombogenic substances
Prostacyclin (PGI2),
nitric oxide,
tissue plasminogen activator,
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 (bing 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 fbrinogen. 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
Thrombocytopenia, prolonged PT/PTT, decreased fibrinogen, elevated D-dimers
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 mucous 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
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, bronchogenic 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
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
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 FSH/LH ratio, 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, DP508 on chromosome 7. Recurrent pseudomona/staph infections, chronic bronchitis, bronchiectasis, atrophy of pancreatic ducts, pancreatic insuficiency, fat malabsorbtion, steatorrhea, infertility, meconium ileum, elevated NaCl sweat test
Deficiency of phenylalanine hydroxylase. Mental retardation by 6 months, light-colored hair and skin, musty odor. Avoid aspartame, monitor pregnancy
"Black Homo" homogentisic acid oxidase deficiency. Black urine, black cartilage
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, hypersplenism, lymphadenopathy, osteoporosis
Glycosaminoglycans acumulation. Mental retardation, cloudy cornea, coarse facial features, hepatosplenomegaly, skeletal deformities
Familial hypercholesterolemia
Mutation on LDL receptor gene on chromosome 19. Xanthomas, xanthelasmas, atherosclerosis
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
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
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
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, 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
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 isotype 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 selectins 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
Fc portion of IgG, c3b, C reactive protein
Chediak-Higashi syndrome
Defect of microtubule polymerization causes defect in chemotaxix and degranulation. Partial albinism, peropheral neuropathy
NADPH oxidase deficiency. No production of superoxide for respiratory burst. Recurrent catalase+ infections, negative nitroblue tetrazolium test
Arachidonic acid products
AA produced 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
C3a, C5a. Directly stimulate histamine release from basophils, mast cells and platelets
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
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
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
Uterine muscle contraction (cause pf primary amenorrhea)
gamma interferon
Produced by CD4 TH1 cells and NK cells. Activates macrophages; antiviral properties; class I and class II antigens; increases IL-2, IL-12 production by CD4 cells
Produced by CD4 cells. T cell growth factor. Promotes B cell and NK cell proliferation
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
Gastric CA, Esophagus
Cigarette smoke
Larynx, ling, renal cell carcinoma, transitional cell carcinoma
Polycyclic aromatic hydrocarbons
Bronchogenic CA
Bronchogenic CA, mesothelioma
Chromium and nickel
Bronchogenic CA
Squamous cell CA of skin and lung, angiosarcoma of liver
Vinyl chloride (PVC)
Liver angiosarcoma
Alkylating agents
Leukemia, lymphoma
Leukemia, lymphoma
Bladder CA
Liver centrilobular necrosis
Adult T-cell leukemia
Hepatocellular CA
Burkitt's lymphoma, nasopharyngeal CA
Cervical CA (16, 18)
Kaposi sarcoma
hst-1 & int-2
Cancer of stomach, breast, bladder and melanoma; produces growth factors; overexpression
Astrocytoma; produces PDGF; overexpression
SCC of lung; produces EGF receptor; overexpression
Breast, ovary and lung CA; produces EGF receptor; amplification
Breast; produces EGF receptor; overexpression
MEN II & III, medullary thyroid CA; produces glial neurotrophic factor receptor; Point mutation
CML, ALL; produces signal transduction proteins; translocation t(9:22), Philadelhpia chromosome
Lung, pancreas and colon; produces GTP binding proteins; Point mutation
Burkitt lymphoma; produces nuclear regulatory protein; translocation t(8:14). When associated to p53 apoptosis; when associated to bcl-2 inhibits apoptosis
Small cell lung CA; produces nuclear regulatory protein; amplification
Neuroblastoma; produces nuclear regulatory protein; amplification
Mantle cell lymphoma; produces cyclin D protein; translocation t(11:14)
Melanoma; produces cdk; amplification
Normally prevents apoptosis. Follicular and undiferentiated lymphomas t(14:18). Chromosome 14: Ig heavy chain; chromosome 18 bcl-2
gastrointestinal stromal tumor
Normally prevents a cell with damaged DNA from entering S-phase by inhibiting cyclin/cdk. Colon, breast, CNS, lung. On chromosome 17
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
Trophoblastic tumors, chroriocarcinoma
Medullary CA of thyroid
lung, pancreas, stomach, breast, colon
Ovarian CA
Pancreatic CA
Placental alkaline phosphatase
Prostatic acid phosphatase
Prostate CA
Prostate CA
Alkaline phosphatase
Metastasis to bone, primary billiary cirrhosis
Chr 3p. Von Hippel Lindau, renal cell CA
WT-1, WT-2
11p. Wilm tumor
17q. Hereditary breast and ovarian CA
13q. Hereditary breast CA
5q. Adenomatous polyps and colon CA
18q. Colon CA
17q. Neurofibromatosis
22q. Acoustic neuromas and meningiomas
Down Syndrome
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
Hepatocellular CA
Ulcerative colitis
Colonic adenocarcinoma
Malignant lymphomas
Non-Hodgkin's, Kaposi
Dysplastic nevus
Malignant melanoma
Small cell lung CA paraneoplastic syndromes
Cushing's (ACTH), SIADH (ADH)
Squamous cell lung CA paraneoplastic syndrome
Hypercalcemia (PTH-like peptide), TGF-b, TNF, IL-1
Renal cell CA paraneoplastic syndrome
Polycythemia (EPO)
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)
Hepatocellular CA
Bence Jones protein
Multiple Myeloma (Ig light chains in urine)
Pituitary (ACTH, Cushings), parathyroid (hypercalcemia), pancreas (zollinger-ellison, insulinoma)
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 phspholipase (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
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 H2O2 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 triglycerides 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
Transient ischemic attack
Reversible synptoms last less than 24 hours. Due to platelet thrombi or atheroemboli
Infarction stroke
85% of strokes. Can be thrombotic (atherosclerosis) white infarct or embolic (thromboemboli or atheroemboli) hemorrhagic infarct
Clinical features of medial cerebral artery stroke
Contralateral hemiparesis and sensory loss, aphasia if Broca area in the left hemisphere is involved, deviation of head and eyes toward side of lesion
Types of hemorrhagic strokes
Intraparenchymal, epidural, subdural, subarachnoid. Hemorrhagic strokes are 15% of all strokes
Causes of hemorrhagic stroke
Hypertension is MCC due to formation of microaneurysms that tend to rupture in basal ganglia or cerebellum. Arteriovenous malformations, amyloid, neoplasms, vasculitides
Clinical features of hemorrhagic stroke
Acute onset of severe headache, nausea, vomiting and coma
Epidural hemorrhage
Due to trauma and skull fracture with tear of middle meningeal dural artery. "Talk and die" syndrome. Leads to herniation if not promptly evacuated
Subarachnoid hemorrhage
MCC: ruptured berry aneurysm. Sudden thunderclap headache, nuchal rigidity, neurological deficits and coma
Berry aneurysms
Thin-walled saccular outpuchings consisting of intima and adventitia only. Cause of subarachnoid hemorrhage. Associated with Marfan, Ehlers-Danlos and adult polycystic kidney disease
Spina bifida occulta
Bony defect of vertebral arch
Bony defect with outpuching of the meninges
Defective bony arch with outpuching of meninges, spinal cord and spinal roots. May lead to paraplegia and urinary incontinence
Defective bony arch with complete exposure of spinal cord. May lead to paraplegia and urinary incontinence
Multiple sclerosis
Chronic relapsing-remitting episodes of demyelination in brain and spinal cord with progressive neurological deficits. Blurred vision or loss of vision, diplopia and vertigo, loss of sensation or weakness in one leg, hemiparesis. TH1 cytokines (IF-g, TNF) facilitate attack; TH2 cytokines (IL-4, IL-10) retard attack.
Parkinson disease clinical features
Loss of dopaminergic neurons in the substantia nigra. Resting tremor, rigidity and akinesia, expressionless face. Rx.: levodopa
Microscopic features of Parkinson disease
Lewy bodies: intracytoplasmic round eosinophilic inclusions that contain alpha-synuclein; EM shows filaments of cytoskeletal origin
Huntington disease clinical features
Degeneration of GABAnergic neurons of caudate nucleus. Chrorea, dementia between ages 20-40. Triplet repeat CAG and features of genetic anticipation and imprinting
Clinical features of Alzheimer disease
MCC of dementia. Insidious inset of memory impariment, alterations in mood and behavior, aphasia and apraxia
Microscopic features of Alzheimer disease
Amyloid precursor protein (APP gene) on chromosome 21 (Down syndrome). AB amyloid from the APP protein. Senile plaques: AB amyloid tangled with neuritic processes, microglia and astrocytes. Neurfibrillary tangles: intraneuronal aggregates of paired helical filaments protein.
Metyrapone stimulation test
Metyrapone blocks 11OHase which stimulates ACTH and 11-deoxycortisol and decreases cortisol. If ACTH increases and 11-deoxycortisol decreases the problem is adrenal insuficiency. If both increase, the problem is pituitary insuficiency. If 11-deoxycortisol or ACTH dont change look for adrenal or ectopic Cushing's.
High dose dexamethasone suppression test
Dexamethasone is a cortisol analog and should suppress ACTH and cortisol. If it does suppress cortisol its pituitary Cushing's. If it doenst, its adrenal or ectopic Cushing's
Clinical features of hyperthyroidism
Tachychardia, palpitations, atrial fibrillation, systolic hypertension, nervousness, diaphoresis, tremors, diarrhea, weight loss. High free T4 and decreased TSH (if primary) or increased TSH (if secondary)
Graves disease
IgG autoantibodies stimulate TSH receptors. Signs and symptoms of hyperthyroidism plus goiter, exophthalmus and pretibial myxedema (due to glycosamynoglycan deposition)
Effect of oral contraceptives and anabolic steroids on binding proteins
Contraceptives increase binding proteins and increase total levels of the hormone with normal TSH or ACTH. Anabolics do the opposite. Increased total T4 or total cortisol with normal TSH or ACTH indicates contraceptives. Decreased total T4 or cortisol with normal TSH or ACTH indicates anabolic steroids.
Clinical features of hypothyroidism
Fatigue, cold sensitivity, decreased cardiac output, myxedema, constipation, anovulatory cycles. Low free T4 with high TSH (primary) or low TSH (secondary)
Congenital hypothyroidism. Mental retardation, failure to thrive, stunted bone growth.
Hashimoto thyroiditis
Anti-microsomal antibodies against thyroid gland produces hypothyroidism. Lymphocytic inflamation with germinal centers
Subacute thyroiditis
Preceded by viral illness. Granulomatous inflamation
Reidel thyroiditis
Destruction of the thyroid gland by dense fibrosis. Irregular hard thyroid that is adherent to trachea (dyspnea) and esopahgus (dysphagia)
Thyroid adenoma
Painless solitary cold nodule that may be functional
Papillary thyroid carcinoma
80% of malignant thyroid tumors. Papillary pattern, psammoma bodies, clear "orphan Annie" nuclei. Lymphatic spread to cervical nodes is common
Follicular thyroid carcinoma
15% of malignant thyroid tumors. Hematogenous metastasis to bone or lungs
Medullary thyroid carcinoma
5% of malignant thyroid tumors. Arises from C cells and produce calcitonin. May be associated with MEN II
Anaplastic thyroid carcionoma
Firm enlarging mass that metastasizes to trachea and esophagus and causes dyspnea and dysphagia
Primary hyperparathyroidism
Excess PTH with hypercalcemia caused by parathyroid adenoma (80%), hyperplasia (15%) or paraneoplastic syndromes (lung SCC and renal cell carcinoma). High serum Ca+ and PTH, kidney stones, osteoporosis, short QT interval.
Secondary hyperparathyroidism
Caused by chronic renal failure (no phosphate excretion increases serum phosphate, decreasing Ca+ and increasing PTH), chronic renal failure also causes deficiency of alpha-1-hydroxylase and vitamin D. Vitamin D deficiency and malabsorption
Functions of PTH
Increase reabsorption of Ca+ in distal tubule, decreases phosphate reabsorption in proximal tubule, increases alpha-1-hydroxylase in proximal tubule, binds to PTH receptor on osteoblast releasing IL-1 (osteoclast activating factor) to activate osteoclast resorption
Due to surgical removal of glands or DiGeorge syndrome. Hypocalcemia with low PTH, tetany, prolonged QT interval
Hyperprolactinemia produces galactorrhea, amenorrhea (tumor mass inhibits GnRH) and infertility
GH producing adenoma
High GH and somatomedin C (IGF-1) produce gigantism (in children, tall stature with long extremities) or acromegaly (in adults, prominent jaw, flat forehead, enlarged hands and feet, diabetes and visceromegaly)
Sheehan syndrome
Ischemic necrosis of pituitary secondary to post partum hypotension results in panhypopituitarism
Diabetes insipidus
Hypotonic polyuria, polydipsia, hypernatremia, dehydration. Central DI is due to lack of ADH. Nephrogenic DI is due lack of renal response to ADH.
Excesive ADH. Oliguria, water retention, hyponatremia, cerebral edema. Due to paraneoplastic syndrome (lung SCC) or trauma
Clinical features of Cushing's syndrome
Thin extremeties (protein catabolism), truncal obesity and buffalo hump (hyperglycemia increases insulin with fat deposition), purple stria (low collagen in vessels), hyperlipidemia (hormone-sensitive lipase), hirsutism, hypertension and hypokalemic alkalosis (high aldosterone).
Differentiation of Cushing's syndrome
High ACTH with dexamethasone suppression --> pituitary. High ACTH without dexamethasone suppression --> ectopic (lung SCC). Low ACTH --> adrenal. Low ACTH with low cortisol and adrenal atrophy --> steroid therapy (MCC). High ACTH produces skin pigmentation in pituitary and ectopic.
Conn syndrome
Adrenocortical adenoma causes hypertension, hypernatremia, hypokalemia, metabolic alkalosis, tetany. High aldosterone and low renin
Waterhouse-Friderichsen syndrome
Bilateral hemorrhagic infarction of the adrenals associated with menigococcemia. DIC, hypotension, shock.
Addison disease
Autoimmune destruction of adrenal cortex due to abrupt withdrawal of corticosteroids, miliary TB or meningoccemia. Weakness, hyperpigmentation of skin (high ACTH), hypotension, hypoglycemia, poor response to stress
Catecholamine-producing benign tumor of the adrenal medulla. Severe headaches, tachycardia, palpitationss, diaphoresis, anxiety, hypertension. Associated with MEN II. Elevated urinary vanillylmandelic acid (VMA) and catecholamines.
Tumors of the pituitary (non-functioning), parathyroids (hypercalcemia), and pancreas gastrinoma (zollinger-ellison)
Medullary carcinoma of thyroid, pheochromocytoma, parathyroid hyperplasia or adenoma
Pathophysiology of diabetic ketoacidosis
Hyperglycemia (due to increased glycogenolysis and gluconeogenesis). Ketone bodies (low insulin and high cortisol/epinephrine activate hormone-sensitive lipase, B-oxidation and ketogenesis). Osmotic diuresis and volume depletion with loss of potassium. Dilutional hyponatremia due to osmotic effect of hyperglycemia. Low insulin fails to activate lipoprotein lipase leading to hypertriglyceridemia.
Pathophysiology of diabetic vascular disease
Non-enzymatic glycosylation and arteriosclerosis produces ischemic injury and diabetic foot. Accelerated atherosclerosis, abdominal aortic aneurysms and MI.
Pathophysiology of diabetic ocular disease
Cataracts due to conversion of glucose into sorbitol by aldose reductase in the lens. Retinopathy with microaneurysms (non-proliferative) and neovascularization (proliferative)
Pathophysiology of diabetic neuropathy
Osmotic destruction of Schwann cells with decreased peripheral sensitivity leads to pressure ulcers on bottom of diabetic foot
Features of tracheoesophageal fistula
Blind esophagus is most common. Cyanosis, choking, vomit after feeding and polyhydramnios
Plummer-Vinson syndrome
Middle age women, esophageal webs with dysphagia to solids, iron deficiency anemia, increased risk of carcinoma
Dysphagia to solids
Esophageal webs in Plummer Vinson syndrome, obstruction due to cancer, Barret esophagus, mitral stenosis
Dysphagia to solids and liquids
No peristalsis. Miastenia gravis, CREST, achalasia
Clinical features of achalasia
Failure of LES to relax due to missing ganglion cells with lack of peristalsis. Dysphagia to solids and liquids, proximal esophageal dilation with bird-beak sign
Mallory-Weiss syndrome
Painful laceration at gastroesophageal junction due to severe prolonged vomiting in alcoholics or bulimia. Hematemesis. Complication: Boerhaave syndrome (esophageal rupture)
Esophageal varices
Dilated branches of left gastric vein secondary to portal hypertension in cirrhosis. Massive unpainful hematemesis.
Reflux esophagitis
Esophageal irritation to due reflux gastric secretions. Heartburn, regurgitation. Associated with Barret's esophagus
Barret esophagus
Squamous-columnar dysplasia of distal esophagus due to gastric reflux. Associated with adenocarcinoma
Esophageal squamous cell carcinoma
Most common in the world, second most common in US. Due to heavy smoking, alcohol, Plummer-Vinson. Progressive dysphagia to solids, bleeding, weightloss
Esophageal adenocarcinoma
Most common in US. In the distal esophagus. Associated with Barret esophagus dysplasia.
Pyloric stenosis
Non-bile projectile vomiting in the second week of life with palpable abdominal olive mass. Associated with Turner and Edwards.
Menetier disease
Hypertrophic rugal folds in body and fundus. Hyperplasia with replacement of parietal and chief cells with decreased acid production, protein loss due to lack of acid to activate pepsinogen and increased risk of gastric adenocarcinoma
Zollinger-Ellison syndrome
Pancreatic gastrin-producing gastrinoma. Hypertrophic rugal folds with increased acid secretion and multiple intractable peptic ulcers
Acute hemorrhagic gastritis
Inflamation and hemorrhage of gastric mucosa due to acid-induced mucosal breakdown. Epigastric abdominal pain, hemorrhage, hematemesis, melena. Caused by aspirin/NSAID (inhibits COX/PGE2), alcohol, smoking, postsurgery, burns.
Stress ulcers
Multiple small superficial ulcers caused by NSAIDs, severe stress, sepsis, shock
Chronic gastritis type A
Autoantibodies against parietal cells and/or intrinsic factor. Decreased acid secretion, increased serum gastrin (G-cell hyperplasia), pernicious anemia. Mucosal atrophy with rugal fold loss and chronic lymphoplasmacytic infiltrate. Increased risk of adenocarcinoma
Chronic gastritis type B
Urease-producing curved gram negative rod H. pylori visible with silver stain. Chronic inflamation with lymphoid follicles. Duodenal and gastric peptic ulcers associated with adenocarcnimoa
Duodenal peptic ulcer
Burning epigastric pain 1-3 hours after eating which is relieved by food. Associated with H. pylori (100%), increased gastric secretions. Anterior wall of proximal duodenum.
Gastric peptic ulcer
Burning epigastric pain which worsens with eating. Associated with H, pylori (75%). Small solitary punched-out ulcers in lesser curvature of the anthrum
Etiology and clinical features of gastric carcinoma
Asymptomatic until late in course. Epigastric abdominal pain, achlorydia, weight loss, ocult bleeding and iron deficiency anemia. Smoked fish and nitrosamines, H. pylori, chronic atrophic gastritis, smoking, Menetier.
Microscopic features of gastric carcinoma
Large irregular ulcer with necrotic base. Signet-ring cells (nucleous displaced to the periphery by intracellular mucin) and Linitis plastica (leather bottle-like stomach)
Virchow (sentinel) node
Left supraclavicular non-tender mass and epigastric distress due to gastric carcinoma metastasis
Krukenberg tumor
Gastric carcinoma metastasis to ovary with signet-ring cells on ovary
Twisting of bowelon its vascular mesentery resulting in obstruction and infarction
Telescoping of proximal into distal segment of bowel. Bloody stools, colic pain, infants.
Hirchsprung disease
Congenital absence of ganglion cells in Auerbach and Meissner plexuses of rectum and sigmoid colon. Delayed passage of mecomium, constipation, abdominal distention, vomiting, affected segment is narrow with proximal megacolon
Celiac sprue
Hypersensitivity to gluten with loss of small bowel villi and malabsorption. Abdominal distention, bloating and flatulence, steatorrhea. Associated with dermatitis herpetiformis
Crohn disease
Acolic pain with episodes of bloody diarrhea. Terminal ileum most common site. Discontinuous spread and ulcers with intervening normal mucosa, linear fissures, noncaseating granulomas, transmural inflammation and transmural sign on barium studies.
Ulcerative colitis
Continuous extensive ulcerations and pseudopolyps of rectum and colon with crypt abscesses in mucosa and submucosa. Associated with toxic megacolon and colon cancer. HLA-B27, arthritis, spondylitis
Ischemic bowel disease
Ischemia of the bowel secondary to atherosclerosis, thrombosis or shock. Abdominal pain and bloody diarrhea.
Pseudomembranous colitis
Inflammatory pseudomembranes in intestines due to C. difficile overgrowth secondary to clindamycin therapy.
Periumbilical pain that subsequently localizes to the right lower quadrant with leukocytosis.
Meckel diverticulum
Asymptomatic congenital remnant of the vitelline (omphalomesenteric) duct. MCC of iron deficiency anemia in newborn.
Colonic diverticulosis
Out pouching and herniation of mucosa and submucosa through the muscularis propria. Most common in sigmoid colon. Left lower quadrant discomfort, occult bleeding and iron deficiency anemia. Complications: diverticulitis, fistulas
Adenomatous colonic polyps
Benign with adenocarcinoma potential. Commonly asymptomatic, occult bleeding with iron deficiency anemia. Sessile, villous is most malignant. Hemocult positive stools
Bowel obstruction
Colic pain, abdomen distention with no rebound tenderness, constipation, obstipation, step-ladder appearance on x-ray. Causes: adhesions from surgery (MCC), duodenal atresia, Hirchsprung.
Familial adenomatous polyposis
Autosomal dominant mutation on APC gene. Thousands of colonic adenomatous polyps. Invasive adenocarcinoma by age 40
Gardner syndrome
Variant of FAP with multiple osteomas, fibromatosis, epidermal inclusion cysts
Autosomal dominant mutation of DNA mismatch repair gene
Colon adenocarcinoma
Third most common in terms of incidence and mortaliy. Risk factors low-fiber diet, ulcerative colitis, FAP. Right colon presents with melena and iron deficiency anemia. Left colon presents with obstruction and reduced caliber stools
Carcioind tumor
Serotonin-producing tumor in appendix (MC) or terminal ileum produces metastasis to liver with subsequent heart carcinoid disease (tricuspid insufficiency, pulmonary stenosis). Diarrhea, flushing, bronchospasm, wheezing, fibrosis. Dx.: urinary 5-HIAA
Clinical features of acute pancreatitis
Stabbing epigastric abdominal pain radiating to the back, shock, hypocalcemia. Caused by gallstones, alcohol, hypercalcemia. Elevation of serum amylase and lipase
Microscopic features of acute pancreatitis
Liquefactive necrosis, acute inflammation, fat necrosis
Complications of acute pancreatitis
ARDS, DIC, pseudocyst, pancreatic calcifications
Clinical features of chronic pancreatitis
Abdominal pain, pancreatic insufficiency and malabsorption in middle age alcoholics. Chronic inflammation, atrophy and fibrosis.
Clinical features of type I diabetes
Polydipsia, polyuria, polyphagia, dehydration and electrolyte imbalance, metabolic ketoacidosis. Represents 10% of diabetes cases, associated to coxackie infection and autoimmune destruction of beta cells, HLA-DR3, DR4 and DQ
Clinical features of type II diabetes
90% of cases. Reduced insulin secretion and peripheral resistance to insulin. Polydipsia, polyuria, polyphagia.
Vascular pathology in diabetics
Major risk factor for atherosclerosis, MI, stroke. Atrophy of skin and loss of hair in lower extremities, claudication, nonhealing ulcers, gangrene, hyaline arteriosclerosis
Diabetic nephropathy
First sign is microalbuminuria. Hyaline arteriosclerosis of afferent and efferent arterioles. Diffuse nodular glomerulosclerosis and renal failure
Diabetic retinopathy
Nonproliferative phase: microaneurysms, retinal hemorrhage and exudates. Proliferative: neovascularization. Cataracts.
Lab findings in type 2 diabetics
Increased glucose, insulin and C peptide
Lab findings in type 1 diabetics
Increased glucose, low insulin and C peptide
Lab findings in insulinoma
Low glucose, high insulin and C peptide
Lab findings in self-injection of insulin
low glucose, high insulin, low C peptide
Produces insulin. Hypoglycemia, elevated insulin and C-peptide. Rx.: glucose
Produces gastrin. Zollinger-Ellison: high gastrin, high gastric acid, intractable peptic ulcers
Produces somatostatin which inhibits insulin secretion (diabetes), gastrin secretion (hypochlorydia), cholecystokinin secretion (gallstones and steatorrhea)
Pancreatic adenocarcinoma
Abdominal pain, migratory thrombophlebitis, obstructive jaundice and clay colored stools. Most common site: pancreatic head. Tumor markers: CEA and CA19-9
Clinical features of gallstones
Right upper quadrant colic pain. Obesity -->cholesterol stones. Bilirubinate stones --> hemolytic anemias and cirrhosis. Complications: cholecystitis, choledocholithiasis, obstruction, pancreatitis.
Acute cholecystitis
Right upper quadrant colic pain, nausea, vomiting, fever, leukocytosis. Complications: gangrene, perforation, peritonitis.
Ascending cholangitis
Bacterial infection of bile ducts. Biliary colic, jaundice, high fever and chills
Causes of unconjugated hyperbilirubinemias
CB/total ration is < 20%. Hemolytic anemias, inneffective erythropoiesis, physiologic jaundice of newborn, Gilbert, Crigler-Najjar
Gilbert syndrome
Unconjugated bilirubinemia due to bilirubin glucoronosyltransferase (UGT) deficiency. Deficient conjugation. Jaundice is related to stress, fasting, infection.
Crigler-Najjar syndrome
Unconjugated bilirubinemia. Type 1 - fatal kernicterus, type 2 - jaundice. Glugoronosyltrasnterase absence or deficiency.
Dubin-Johnson syndrome
Conjugated bilirubinemia. Defect in canalicular transport with deficient excretion. Black pigmentation of liver.
Causes of conjugated hyperbilirubinemias
Dubin-Johnson, biliary tract obstruction by gallstones or tumors, PBC, primary sclerosing cholangitis
Billiary tract obstruction
By gallstones, pancreatic tumors. Conjugated bilirubinemia. Jaundice, pruritus, coluria, clay-colored stools, abdominal pain and fever
Primary biliary cirrhosis
Inflamation and granulomatous destruction of intrahepatic bile ducts. Middle age woman presents with obstructive jaundice, pruritus, xanthomas, xanthelasmas and high cholesterol. Anti-mitochondrial autoantibodies.
Fibrosis by Ito cells and regenerating nodules of hepatocytes. Due to alcohol, HBV, HCV, biliary tract disease, hemochromatosis. Leads to portal hypertension with ascites, splenomegaly, esophageal varices, hemorrhoids, hepatic encephalopathy, gynecomastia, hypoalbuminemia, low clotting factors, hepatorenal syndrome.
Acute HBV markers
HBsAg+, HBeAg+, HBcAb IgM+
HBV window period markers
HBcAb IgM+
HBV prior infection markers
HBcAb IgG+, HBsAb IgG+
HBV immunization markers
HBsAb IgG+
HBV chronic infection markers
HBsAg+, HBeAg+, HBcAb IgM+, HBcAb IgG+
Alcoholic liver disease
AST>ALT. Fatty change. In case of alcoholic hepatitis - RUQ pain, hepatomegaly, jaundice.
Wilson disease
Accumulation of copper due to decreased liver excretion. Fatty change, chronic hepatitis, micronodular cirrhosis, Kayser-Fleischer cornea rings, neurological manifestions. Low ceruloplasmin, high free copper, low total copper, high urine copper.
High levels of iron due to increased absorption or secondary to transfusions. "Bronze diabetic", CHF. High ferritin and serum iron, low TIBC. HCC in 30%. Liver biopsy with Prussian blue stain.
Hepatic vein thrombosis caused by polycythemia, contraceptives, pregnancy. Abdominal pain, hepatomegaly, ascites.
Due to cirrhosis, HBV, HCV, alcohol, hemochromatosis. Tumor marker - alpha-fetoprotein.
Target cells
increased RBC membrane. Hemoglobinopathies, thalassemia, liver disease.
Irregular spicules on surface. Abetalipoproteinemia
Decreased RBC membrane. No central area of pallor. Spherocytosis
RBC fragments. Microangiopathic hemolytic anemia, trauma
Bite cells
RBC with removed bits of cytoplasm. G6PDH deficiency.
Sickle cells
Sickle cell anemia
Howell-Jolly bodies
Remnants of nuclear chromatin. Severe anemias or patients without spleen
Ring sideroblasts
Trapped iron in mitochondria. Prussian-blue stain. Sideroblastic anemia
Heinz bodies
Denatured Hb. G6PDH deficiency
Basophilic stipling
RNA remnants. Lead poisoning
Hypersegmented neutrophil
Megaloblastic anemia
EPO stimuli
Low SaO2 (hypoxemia, anemia < 7gm/Dl, left shifted O2 curve
Immature RBC with no nucleous and bluish color in peripheral blood indicate effective erithropoiesis. Require 24 hours to become mature.
Reticulocyte normal and corrected count
Normal reticulocyte count is 1.5%. Corrected count is Hct/45 * reticulocyte count. >3% --> marrow responds well. <3% marrow is not well. If polychromasia (shift cells) divide corrected count by two because shift cells take double the time to mature
Signs of anemia
Palpitations, dizziness, angina, pallor, weakness
Hypochromic RBCs
Increased central pallor
MCV < 80
Iron deficiency, thalassemia, AOCD, Sideroblastic
MCV 80-100, low reticulocyte count
Marrow failure, aplastic anemia, leukemia, renal failure, AOD
MCV 80-100, high reticulocyte count
Sickle cell, G6PDH deficiency, spherocytosis, AIHA, PNH
MCV > 100
Folate or B12 deficiency
Causes of iron deficiency anemia
Ulcers, menstrual bleeding, left colon cancer, elderly and poor children, malabsorption, gastrectomy, hookworm, Plummer-Vinson
Low serum iron, % saturation and serum ferritin with high TIBC
Iron deficiency anemia
Low serum iron, TIBC and % saturation with high serum ferritin
High serum iron, serum ferritin and % saturation with low TIBC
Sideroblastic anemia
Iron is trapped in bone marrow macrophages due to high levels of IL-1 and lactoferrin. High ferritin and low TIBC.
Hb Barts
Carrier has one α gene deletion, asymptomatic. Α-Thal trait has two deletions. HbH disease three deletions with high HbH and Heinz bodies. Hydrops fetalis, four deletions, lethal, high Hb Barts
Minor, asymptomatic, 8% HbA2 and 5% HbF. Major - develop symptoms 6 months after birth as HbF declines, jaundice, bilirubin gallstones, secondary hemochromatosis due to life-long transfusions, CHF, crecut skull x-ray, target cells. 90% HbF and HbA2
Lead poisoning anemia
Sideroblastic anemia. Lead denatures ferrochelatase, ALA dehydrse and ribonuclease (coarse basophilic stipling). Ringed sideroblasts and basophilic stipling. Lead colic, peripheral neuropahty, cerebral edema, learning disabilities, bone in epiphysis on x-rays. high serum Pb, high urine δ-ALA, high serum iron, ferritin and %saturation with low TIBC. Risk fators: Pb paint, battery factory, pottery painter.
Iron overload anemia
Sideroblastic anemia with ringed sideroblasts. Alcoholism (MCC), pyridoxine deficiency (required by ALA synthase), isoniazid treatment. High serum iron, % saturation, ferritin and decreased TIBC.
Factors that induce and prevent sickling
Deoxygenation of Hb/right shifting dissociation curve (acidosis), increasing HbS concentration (dehydration), low O2 tension (altitude and renal medulla). HbF left shifts dissociation curve and prevent sickling (hydroxeurea Rx)
Pathophysiology of sickle cell disease
Valine subsitutes glutamic acid in position 6 of β Hb chain causing sickling and thrombi that occlude vessels (painful crisis), hand-foot swelling, autosplenectomy with Howell-Jolly bodies and increased risk of infections by encapsulated orgainsms, Salmonella osteomyelitis, parvovirus B19 aplastic crisis.
Pathophysiology of G6PDH deficiency
Mutation causes defective protein folding with low G6PDH activity and low levels of reduced gluthathione needed to neutralize ROS. Oxidative stress, oxidative drugs (primaquine, sulfonamides, anti-TB), bacterial infections and fava beans cause red cell damage and hemolysis with Heinz body formation (seen with methylene blue or crystal violet stains)
Pathophysiology of spherocytosis
Spectrin defect with decrease in RBC membrane leads to circular RBCs which are removed by macrophages in the spleen (extravascular hemolysis). Triad of anemia, splenomegaly and jaundice with risk of bilirubinate gallstones. Increased osmotic fragility test.
Pathophysiology of AIHA
IgG autoantibodies against Rh antigens on RBC with macrophage removal in spleen cause splenomegaly. Differentiate from hereditary spherocytosis with positive direct Coombs test
Pathophysiology of PNH
Low levels of decay accelerating factor (DAF) are not able to normally inhibit C3 convertase with increased sensitivity of cells to complement lysis. Slow breathing at night (retains CO2) and exercise produce acidosis which activates the complement system with pancytopenia and increased risk of aplastic anemia, leukemia and venous thrombosis
Direct Coomb's test
Detects IgG or C3 on surface of RBCs. Positive in AIHA, negative in hereditary spherocytosis.
Indirect Coomb's test
Detects autoantibodies in the serum. Often positive in AIHA
Pathophysiology of microangiopathic hemolytic anemia
RBCs are damaged by calcium in stenotic valves (aortic stenosis MCC), fibrin clots in DIC and platelet plugs in ITP and HUS. Presence of schistocytes.
Sites for reabsorption of iron, folate and B12
Iron: duodenum (Bilroth II, vitamin c deficiency and malabsorption syndromes produce deficiency). Folate: jejunum (contraceptives and alcohol decrease absorption). B12: terminal ileum (pernicious anemia, Crohn's and terminal ileum resection decrease absorption)
Pathophysiology of megaloblastic anemia
Methyl THF is needed to make methylcobalamine to convert homocysteine into methione by methylTHF-homocysteine methyl transferase (requires cobalamine). Methylene THF is required by thymidilate synthetase to make nucleic acids. B12 is needed by methylmalonyl CoA mutase to make succinyl CoA.Tetrahydrofolate is made by dihydrofolate reductase (blocked by methotrexate and trimethropin). Deficiency of folate or B12 produces megaloblastic anemia with hypersegmented neutrophils (no nucleic acid synthesis), homocystinuria and methylmalonic aciduria.
Causes of folate deficiency
Alcoholism (not beer), pregnancy, methotrexate, trimetrhoprim, phentoyn, birth control pills, celiac disease, leukemia
Causes of B12 deficiency
Pernicious anemia, pure vegan diet, Crohn's disease, chronic pancreatitis (cant cleave R factor from saliva which protects B12), D. latum
Schilling's test
Non-radioactive intramuscular B12 to saturate transcobalamin followed by radioactivee oral B12. No radioactive B12 detected in 24h urine confirms B12 absorption deficiency. Correct with intrinsic factor (pernicious anemia), pancreatic enzymes (chronic pancreatitis) or antibiotics (bacterial overgrowth)
Heterophile+ infectious mononucleosis
EBV invades B lymphocytes via CD21 receptors with atypical CD8 response, lymphocytosis and paracortex hyperplasia. Fever, sore throat (gray-white membrane on tonsils) and tender lymphadenopathy
Heterophile- infectious mononucleosis
Paul-Bunnell monospot test reaction
IgM (heterophile) antibodies against EBV react with sheep red blood cells - postivie monospot test
Characteristics of acute lymphadenopathy
Tender focal lymphadenopathy = bacterial. Generalized tender lymphadenopathy = viral
Characteristics of chronic lymphadenopathy
Non-tender follicular hyperplasia (rheumatoid arthritis, toxoplasmosis, leukemia). Non-tender paracortical hyperplasia (viruses, drugs, SLE, leukemia).
Leukemoid reaction Vs. leukemia
Leukemoid reaction lacks blast and leukocyte alkaline phosphatase (LAP) (TB, whooping cough). Chronic myelogenous leukemia has low LAP.
General signs and symptoms of leukemia
Normo anemia, thrombocytopenia, leukocytosis or leukopenia, blast cells (>30%=acute), generalized non-tender lymphadenopathy, hepatosplenomegaly, bone pain and fever
Age < 15. Tdt+, CALLA+, cytoplasmic mu+
Mature B ALL
Age < 15. Surface Igs present
B cell CLL
Age > 60. 95% of CLL cases. Differentiated cells are CD19+, CD20+, CD23+, CALLA-
T cell CLL
Age > 60. Mature T cell markers and hypogammaglubulinemia. Lymphocytosis and neutropenia
Adult T cell leukemia
Caused by HTLV-1 retrovirus. Leukemia sypmtoms and signs wih lytic bone lessions and hypercalcemia (osteoclast activating factor)
15-60 years. Myeloblast proliferation. Auer rods are pathognomonic of myeloblasts. T(15;17). Abnormal retinoic acid receptor. Rx.: retinoic acid
15-60 years. Pluripotent cell proliferation. Philadelphia chromosome t(9;22). All cells increased with low LAP
Increased erythroid precursors, hematocrit and viscocity. Decreased EPO. Normal SaO2. Increased basophils with histamine release (pruritus, gastric ulcers), plethora and cyanosis.
Follicular B-cell lymphoma
MC lymphoma. B lymphocytes. t(14;18), Chr 14 has immunoglobulin heavy chain genes, chr 18 has bcl-2 gene (normally inhibits apoptosis).
Burkitt's lymphoma
MC lymphoma in children. Starry-sky. t(8;14). African affects mandible, american affects abdomen
Mycosis fungoides
CD4 T-cells. Generalized prutitic erythematous rash. PAS+
Histiocytosis X
In children. Histiocytes are CD1+
Hodgkin lymphoma
Reed-Sternberg cells are CD15+, CD30+. Fever, night sweats, weight loss, localized lymphadenopathy
Multiple myeloma
Neoplasm of plasma cells. Anemia, bone pain, pathologic fractures, hypercalcemia, renal failure, light-chain amyloids (Bence-Jones protein).
AML translocation
CML philadelphia chromosome translocation. Forms a protein with tyrosine kinase activity
Follicular B-cell lymphoma translocation
Burkitt's lymphoma translocation
Composition of bone
Organic matrix: osteoblasts, osteoclasts, type I collagen, glycoproteins. Inorganic matrix: calcium hydroxyapatite, magnesium, potassium, chloride, sodium
Production of unmineralized bone. High amounts of alkaline phosphatase and PTH receptors to modulate osteoclasts
Bone resorption
Inherited dwarfism. Mutation on fibroblast growth factor receptor 3 inhibits cartilage synthesis at the epiphysial plates with decreased endochondral bone formation and premature ossification of growth plates. Short and thick extremities, large head and trunk.
Osteogenesis imperfecta
Abnormal synthesis of type I collagen. Recurrent fractures and deformities, thin blue sclera, deafness, thin skin and easy bruising
Causes of osteoporosis
Primary causes: estrogen deficiency with high IL-1 activity (postmenopausal, Turner's), genetic factors, lack of exercise, old age, nutritional. Secondary causes: Immobilization, Cushing's, thyrotoxicosis, malnutrition, corticosteroids.
Clinical features of osteoporosis
Bone is normal but in decreased amounts. Bone pain, compression fractures (vertebrae), femoral neck fracture, distal radius fracture.
Radiographic, lab and microscopic features of osteoporosis
Radiolucency of bone (osteopenia). Normal serum calcium, phosphorus and alkaline phosphatase. Thinned cortical and trabecular bone
Treatment of osteoporosis
Estrogen replacement therapy, weight bearing exercise, calcium, vitamin D, biphosphonates, calcitonin
Causes of osteomalacia and rickets
Decreased mineralization of newly formed bone due to abnormal metabolism of vitamin D. Dietary deficiency, intestinal malabsorption, lack of sunlight, renal and liver failure
Clinical features of rickets
Occurs in children. Craniotabes and frontal bossing (skull deformities), deformity of chest wall, pigeon breast, bowing of the legs. Low serum calcium with high alkaline phosphatase and PTH
Clinical features of osteomalacia
In adults, bone pain, fractures of vertebrae, hips and wrist. Low serum calcium, high alkaline phosphatase and PTH
MC pathogen in osteomyelitis
Osteomyelitis in sickle cell disease
Osteomyelitis in drug abusers and diabetics
Clinical features of osteomyelitis
Fever, leukocytosis, localized pain, erythema and swelling
Clinical features of osteoarthritis
Wear and tear joint chondrocyte injury with loss of articular collagen in weight-bearing joints. Stiffness, decreased range of motion, crepitus, pain that worsens with motion, old age. X-ray shows narrowing of joint space and osteophytes.
Clinical features of rheumatoid arthritis
Systemic, chronic inflamatory disease with anti-IgG autoantibodies (rheumatoid factor). Affects hands, wrists and knee, symetrical involvement, morning stiffness that improves with activity. Systemic manifestations: fever, fatigue, lymphadenopathy, rheumatoid subcutaneous skin nodules, Sjogren syndrome (15%)
Microscopic, x-ray and lab findings in rheumatoid arthritis
X-ray: juxta-articular osteoporosis and bone erosions. Micro: Synovitis, pannus (proliferation of synovium and granulation tissue over joint cartilage), radial deviation of wrist, ulnar deviation of fingers. Lab: high ESR, hypergammaglobulinemia, rheumatoid factor (anti-IgG).
Ankylosing spondylitis associations
young males, HLA-B27
Reiter syndrome
Conjunctivitis, chlamydia urethritis, arthritis of ankles and knees, HLA-B27, follows gonococus or chlamydia infection
Causes of gout
Primary (90%) idiopathic. Secondary: Leukemia, renal disease, Lesch-Nyhan, Von Gierke
Clinical features of gout
Exquisite pain in big toe. Negatively birefringent, needle-shaped monosodium urate crystals and neutrophils in aspiration. Complications: joint destruction, uric acid renal calculi, renal failure. Rx.: NSAIDs, colchicine, probenecid allopurinol
Infectious arthritis clinical features
Gonococci MC. Tender, swollen and erythematous joints, monoarticular arthritis. Cloudy sinovial fluid that clots, neutrophils and positive gram stain in aspiration
Clinical features of myasthenia gravis
Autoantibodies against Ach receptors at neuromuscular junction. Ptosis, diplopia, weakness. Associated with thymic hyperplasia and thymomas. Rx.: anticholinesterase agents, thymectomy
Eaton-Lambert syndrome
Paraneoplastic syndrome of SCC of lung. Autoantibodies against the presynaptic Ca+ channels at neuromuscular junction.
Duchenne muscular dystrophy
Absence of dystrophin muscle structural protein. Onset of symptoms by age 5, progressive muscular weakness, heart failure, respiratory insufficiency and infections. High serum CK.
Guillain-Barre syndrome
Preceded by viral illness. Ascending paralysis, loss of deep tendon reflexes. Inflamation and demyelination of peripheral nerves and spinal nerve roots result in muscular weakness
Irregular, completely depigmented patches devoid of melanocytes.
Irregular blotchy patches of hyperpigmentation on the face
Light brown macules on face, shoulders and chest. Increased melanin deposition in the basal layer of the epidermis
Nevocellular nevus (mole)
Benign tumor of melanocytes with sharp well-circumscribed borders
Malignant melanoma
Asymetric, irregular borders, variegated color, large diameter, enlarging, macule, papule or nodule. Risk factors: chronic sun exposure, fair skin, dysplastic nevus syndrome
Acanthosis nigricans
Thickened, hyperpigmented skin in axillae and groin. Associated with malignancy and gastric adenocarcinoma
Well demarcated erythematous plaque with a silvery scale. Epidermal hyperplasia (acanthosis), patchy keratinization with parakeratosis. Rx.: topical steroids and radiation
Autoantibodies against desmosome component desmoglein 3 results in loss of intracellular adhesion (acantholysis) and blister formation. Easily ruptured, flaccid blisters. Immunofluorescence shows net-like pattern of IgG stainning
Bullous pemphigoid
Autoantibodies against hemidesmosome component bullous pemphigoid antigens 1 and 2 result in separation of epidermis from dermis and blister formation. Tense bullae that do not rupture easily. Eosinophils are seen
Dermatitis herpetiformis
IgA autoantibodies against gliadin that deposit in the tips of the dermal papillae with subepidermal clister formation. Microabsecesses with neutrophils are seen
Squamous cell carcinoma of the skin risk factors
Chronic sun exposure, fair complexion, chronic skin ulcers, xeroderma pigmentosa, actinic keratosis
Squamous cell carcinoma of the skin clinical features
Tan nodular mass which ulcerates on sun exposed areas. Micro: nests of atypical keratinocytes invade the dermis, formation of keratin pearls, desmosomes between tumor cells
Basal cell carcinoma of the skin clinical features
Chronic sun exposure, fair complexion, xeroderma pigmontosum. Pearly papules and nodules with heaped up translucent borders, telangiectasia, ulcerations. Palisading growth pattern
Adult polycystic kidney disease
Asymptomatic until middle age. Renal insuficiency, hematuria, hypertension. Abdominal masses and flank pain. Renal failure. Associated with liver cysts, berry aneurysms, mitral prolapse.
Nephritic syndrome
Hematuria, hypertension, azotemia, oliguria, proteinuria <3.5g/day
Nephrotic syndrome
Proteinuria >3.5g/day, hypoalbuminemia, generalized edema, hyperlipidemia
Acute poststreptococal glomerulonephritis light microscopy
Hypercellular glomeruli with neutrophils, red cell casts in renal tubules
Acute poststreptococal glomerulonephritis immunofluorescence
Granular deposits of IgG, IgM and C3 throughout the glomerulus
Acute poststreptococoal glomerulonephritis electron microscopy
subepithelial humps immune complex deposits
Pathogenesis of Goodpasture syndrome
anti-GBM antibodies damage kidneys and lungs. Antigen is collagen type IV
Clinical presentation of Goodpasture syndrome
nephritic syndrome with hemoptysis. Most will develop RPGN
Goodpasture syndrome electron microscopy
GBM disruption
Goodpasture syndrome immunofluorescence
Smooth and linear pattern of IgG and C3 in the GBM
Causes of RPGN
Goodpasture, poststreptococal, SLE, Wegner
RPGN light microscopy
Crescent formation in Bowman's space (macrophages, fibrin parietal endothelial cells)
RPGN immunofluorescence
granular or linear deposits of Ig and complement
RPGN electron microscopy
GBM disruption and discontinuity
IgA nephropathy (Berger disease)
Most common cause of GN. Nephritic syndrome with recurrent hematuria. Associated with celiac sprue and Henoch-Schonlein purpura
IgA nephropathy light microscopy
Mesangial proliferation
IgA nephropathy immunofluorescence
Mesangial deposits of IgA and C3
IgA nephropathy electron microscopy
Mesangial immune complex deposits
MPGN clinical features
Nephiritic or nephrotic. Decreased C3. C3 nephritic factor antibody activates C3 convertase with degradation of C3
MPGN light microscopy
Mesangial rpoliferation with BM thickening and tram tracking (splitting of basemant membrane)
MPGN immunofluorescence
Granular pattern of C3 often with IgG C1q and C4
MPGN electron microscopy
subendothelial and mesangial immune complex deposits
Alport syndrome
X-linked defect in type 4 collagen characterized ny nephritis, hearing loss and ocular abnormalities. EM: alternating thickening and thinning of BM
Membranous GN etiology
85% idiopathic, penicillamine, HBV, HCV, SLE, DM
Membranous GN ligh microscopy
Diffuse membrane-like thickening of capillary walls, baseman membrane projection spikes
Membranous GN immunofluorescence
Granular and linear pattern of IgG and C3
Membranous GN EM
Subepithelial deposits, effacement of podocyte foot processes
Minimal change disease
Nephrotic syndrome in children 2-6 years. EM: effacement of epithelial foot processes. Rx.: corticosteroids
Focal segmental glomerulosclerosis light microscopy
Focal segmental sclerosis and hyalinization of glomeruli
Focal segmental glomerulosclerosis IF
IgM and C3 deposits in sclerotic segments
Mention all nephritic syndrome pathologies
Poststreptococal, Goodpasture, IgA nephropathy, RPGN, MPGN, Alport
Mention all nephrotic syndrome pathologies
MGN, minimal changee disease, focal segmental glomerulonephritis
Features of chronic glomerulonephritis
Renal failure, uremia, anemia, proteinuria, hypertension, azotemia, reduction of GFR, hypocalcemia (no vitamin D), hyperphosphatemia. Hyalinization of glomeruli, fibrosis, atrophy and lymphocytes
Features of acute tubular necrosis
Reversible injury. Oliguria, increased BUN and creatinine, metabolic acidosis and hyperkalemia
Causes of ischemic acute tubular necrosis
hemorrhage, severe renal vasoconstriction, hypotension, dehydration, shock
Causes of nephrotoxic acute tubular necrosis
polymyxin, methicillin, gentamicin, sulfonamides
Clinical features of acute pyelonephritis
E. coli, proteus, kleibsiella, enterobacter. Fever, chills, dysuria, frequency, urgency, costovertebral angle tenderness, pyuria, WBC casts
Types of renal calculi
Calcium oxalate (75%), struvite (asoociated with urea-splitting bacteria - proteus), uric acid (gout, leukemia, acid urine)
Clinical features of renal calculi
Unilateral colic pain, hematuria, obstruction, infection. Calcium stones are raddiopaque.
Clinical features of renal cell carcinoma
Cigarette smoke is risk factor. Hematuria, palpable mass and flank pain
Renal cell carcinoma paraneoplastic syndromes
Polycythemia (EPO), hypertension (renin), Cushing syndrome
Wilms tumor
Mutations in WT-1 and WT-2 suppressor genes. WAGR syndrome - Wilm's tumor, aniridia, genital anomalies, mental retardation
Condyloma acuminatum
Verrucous wartlike lesions on vulva, perineum, vagina and cervix associated with HPV serotypes 6 and 11
Pelvic inflammatory disease
Vaginal discharge (cervicitis), vaginal bleeding (endometritis), bilateral lower abdominal and pelvic pain (salpingitis). Caused by n. gonorrhea and/or chlamydia. Complications: tubo-ovarian abscess, tubal scarring (granulomatous inflamation) with infertility and ectopic pregnancies
Cervical cancer risk factors
Early age of first intercourse, multiple sexual partners, multiple pregnancies, oral contraceptives, smoking
Cervical cancer clinical features
45 years old. Asymptomatic or postcoital bleeding, dyspareunia (painful intercourse), malodorous discharge. Caused by HPV types 16, 18, 31 and 33. Precursor lesion is cervical intraepithelial neoplasia
Presence of endometrial glands and stroma outside the uterus in ovaries, ligaments and pouch of Douglas. Presents with chronic pelvic pain, dysmenorrhea, dyspareunia (painful intercourse), rectal pain, constipation, infertility
Endometrial carcinoma risk factors
Early menarche, late menapause, nulliparity, hypertension, diabetes, anovulation, estrogen-producing tumors, estrogen-replacement therapy, endometrial hyperplasia
Endometrial carcinoma clinical features
55 year old with postmenopausal vaginal bleeding
Polycystic ovarian disease
Females of reproductive age, oligomenorrhea, hirsutism, infertility. Lab: elevated LH, low FSH, high testosterone. Predisposes to endometrial cancer
Ovarian cystadenocarcinoma
65 year old with malignant bilateral ovarian enlargement. Risk factors: BRCA-1. Marker: CA125
Metastatic tumors to the ovary primary sites
Breast, colon, endometrial, gastric "signet-cell" Krukenberg tumor
Hydatidiform mole
Tumor of placental trophoblastic tissue/ Excessive uterine enlargement, vaginal bleeding, high B-HCG. Complete mole: fertilization of an ovum without chromosomes. Partial mole: fertilization by two sperms (one 23X, one 23Y)
Malignant germ cell tumor derived from the trophoblast
Fibrocystic change presentation
Bilateral painful mass in young woman with menstrual variation
Movable mass that changes with mentrual cycles
Breast carcinoma risk factors
BRCA-1, BRCA-2, p53, prior breast cancer, old age, nulliparity, obesity
Breast carcinoma clinical features
Solitary painless mass in old woman with nipple retraction or skin dimpling or fixation to chest wall. Calcification on mamogram. MC variation is invasive ductal carcinoma
Benign prostatic hyperplasia
Decreased caliber and force of stream, urgency, frequency, nocturia, dysuria. PSA is elevated. Rx.: 5-alpha reductase inhibitor
Prostate cancer
Asymptomatic or lower back pain secondary to metastasis. High PSA. Metastasis to pelvic lymph nodes and lumbar spine with high alkaline phosphatase
What will aspiration of a foreign body result in the lung?
Obstruction atelectasis
Presence of fluid, air or tumor in the pleural space results in what type of atelectasis?
Compression atelectasis
Contraction atelectasis is due to what cause?
Fibrosis of the lung
Causes of patchy atelectasis
Lack of surfactant (hyaline membrane disease of newborn or ARDS)
Clinical features of typical pneumonia
Sudden onset, high fever, productive cough, tachypnea, pleuritic chest pain, consolidation on x-ray
Clinical features of atypical pneumonia
Insidious onset, low fever, no cough, no consolidation
Differential diagnosis of rusty sputum
Strep pneumonia, CHF, mitral stenosis, Goodpasture syndrome
Features of sarcoidosis
"GRAIN": gammaglubilinemia, rheumatoid arthritis, ACE increase, interstitial fibrosis, non-casseating granuloma, bilateral lymphadenopathy, hypercalcemia due to vitamin activation by macrophages
Causes of restrictive pulmonary disease
Kyphoscoliosis, obesity, pneumoconiosis, ARDS, pulmonary fibrosis, sarcoidosis
Causes of obstructive pulmonary disease
Asthma, emphysema, chronic bronchitis, bronchiectasis
Lung volumes in obstructive pattern
Increased TLC, FRC and RV. Decreased FEV1, FVC, FEV1/FVC
Lung volumes in restrictive pattern
Decreased, TLC, FEV1, FVC, FRC, RV. Increased or normal FEV1/FVC
Diagnosis criteria for chronic bronchitis
Persistent cough and copius sputum production for at least 3 months in 2 consecutive years
Clinical features of chronic bronchitis
Cough, sputum production, dyspnea, infections, hypoxia, cyanosis, weight gain. "Blue bloater"
Microscopic findings in chronic bronchitis
Hypertrophy of bronchial mucous glands, globlet cell hyperplasia, mucus hypersecretion, bronchial metaplasia
Complications of chronic bronchitis
Recurrent infections, cor pulmonale, lung cancer
Definition of emphysema
destruction of alveolar septa resulting in enlarged air spaces and loss of elastic recoil
Etiology of emphysema
Protease/antiprotease imbalance. Proteases are made by macrophages and neutrophils. Antiproteases are alpha-1-antitrypsin, alpha-1-macroglubulin and secretory leukoprotease inhibitor
Features of centriacinar emphysema
Proximal bronchioles involved, distal bronchioles spared, most common (95%), associated with smoking, worst in apical segments of upper lobes
Features of panacinar emphysema
Entire acinus invololved, alpha-1-antitrypsin deficincy, worse in bases of lower lobes
Clinical features of emphysema
Progressive dyspnea, pursing of lips and accesory muscles, barrel chest, weight loss, "Pink puffer"'
Clinical features of asthma
Wheezing, severe dyspnea, coughing
Microscopic features of asthma
Charcot-leyden crystals, mucous plugs, goblet cell hyperplasia and hypertrophy, eosinophils, edema, hypertrophy of smooth muscle, thick basement membranes
Clinical features of bronchiectasis
cough, fever, malodorous purulent sputum, dyspnea, dilated bronchi extending out to pleura on x-ray
Etiology of bronchiectasis
Bronchial obstruction, necrotizing pneumonia, cystic fibrosis, Kartagener syndrome
Definition of acute respiratory distress syndrome
damage of alveolar epithelium and capillaries resulting in respiratory failure that is unresponsive to O2 treatment
Causes of ARDS
shock, sepsis, trauma, gastric aspiration, radiation, O2 toxicity, drugs, infections
Clinical features of ARDS
dyspnea, tachypnea, hypoxemia, cyanosis, use of accesory respiratory muscles. Bilateral lung opacity on x-ray
Microscopic features of ARDS
interstitial and alveolar edema, interstitial inflamation, loss of type I pneumocytes, hyaline membrane formation
RDS of newborn
Deficiency of surfactant in prematures (<28 weeks) and sons of diabetic mothers. Dyspnea, tachypnea, nasal flaring and cyanosis. Lecithin:sphyngomyelin < 2. Rx.: surfactant and dexamethasone
Causes of pulmonary edema
left heart failure, mitral stenosis, fluid overload, nephrotic syndrome, liver disease
Microscopic features of pulmonary edema
Intra-alveolar fluid, engorged capillaries, hemosiderin-ladden macrophages
Risk factors and genetics of bronchogenic CA
Cigarette smoking, pneumoconiosis, pollution. Oncogenes: L-myc (SCC), K-ras (adeno). Suppressor genes: p53 and Rb
Clinical features of bronchogenic CA
Cough, sputum production, weight loss, anorexia, fatigue, dyspnea, hemoptysis, chest pain. Obstruction may produce emphysema, atelectasis, bronchiectasis or pneumonia
Lung adenocarcinoma
Most common - 35%. More common in women. Peripheral gray mass, scarring and mucin-producing glands
Squamous cell carconima of lung
2nd most common - 30%. More common in males, related to smoking. Centrally located. Invasive squamous cells with desmosomes and keratin production, PTH production
Small cell carcinoma
20%. More common in males, associated to smoking. Central location. Basophilic neurosecretory granules and paraneoplastic syndromes (ACTH, ADH)
Pancoast tumor
Apical tumor causing Horner syndrome (ptosis, miosis, anhidrosis, enopthalmos)
Superior vena cava syndrome
Obstruction, distended head and neck veins, plethora, facial edema
Effects of lung masses within the thorax structures
Pancoast tumor, superior vena cava syndrome, esopahgeal obstruction, recurrent laryngeal nerve hoarseness, Eaton-Lambert syndrome
Sites of metastasis of lung cancer
Adrenals (>50%), liver, brain, bone
Eaton-lambert syndrome
auto-antibodies against presynaptic Ca channels in neuromuscular junction
Metastasis to the lung
Breast (most common)
Lab findings in PAN
p-anca. HBsAg+ in 30%, anemia, leukocytosis
Microscopic features of PAN
Segmental necrotizing vasculitis in three stages: fibrinoid necrosis with neutrophils, fibroblast proliferation, nodular fibrosis with loss of internal elastic lamina
Clinical features of PAN
Affects all organs except lungs. Fever, hematuria/renal failure/hypertension, abdominal pain/GI bleeding, myalgia/arthralgia
Clinical features of Wegner granulomatosis
Bilateral pneumonitis with nodular and cavitary infiltrates, chronic sinusitis, nasopharyngeal ulcerations, renal disease
Microscopic features of Wegner granulomatosis
Necrotizing vasculitis of small vessels (granulomas), necrotizing granulomas of respiratory tract, focal necrotizing glomerulonephritis
Lab findings in Wegner granulomatosis
Treatment of Wegner granulomatosis
Clinical features of temporal arteritis
Throbbing unilateral headache, visual disturbances, jaw claudication
Microscopic features of temporal arteritis
Segmental granulomatous vasculitis with multinucleated giant cells and fragmentation of the internal elastic lamina with intimal fibrosis and luminal thickening
Diagnosis, lab findings and treatment of temporal arteritis
Dx.: biopsy of temporal artery. Lab: increased ESR. Rx.: steroids
Clinical features of Takayasu asteritis
Loss of pulse in upper extremities, visual disturbances, neurologic abnormalities
Microscopic features of Takayasu arteritis
Granulomatous vasculitis with massive intimal fibrosis, thickening of the aortic arch and narrowing of the major arterial branches
Clinical features of Buerger's disease
Severe pain in affected extremity, thrombophlebitis, Raynaud phenomenon, ulceration and gangrene. Associated with heavy cigarette smoking
Microscopic features of Buerger's disease
Recurrent neutrophilic vasculitis with microabseses, segmental thrombosis and vascular insuficiency
Clinical features of Kawasaki disease
Affects children < 4. Acute febrile illness, conjuctivitis, maculopapular rash, lymphadenopathy, coronary aneurysms in 70% of cases
Microscopic features of Kawasaki disease
Segmental necrotizing vasculitis with coronary aneurysms
Diseases that feature Raynaud phenomenon
SLE, CREST, Buerger, atherosclerosis
Raynaud diseasse
Small artery vasospasm resulting in blanching cyanosis of fingers and toes precipitated by cold temperature and emotions
Henoch-Schonlein purpura
IgA-C3 immunocomplexes, IgA nephropathy (Berger disease), palpable purpura on buttocks
Major risk factors for atherosclerosis
Hyperlipidemia, hypertension, smoking, diabetes
Most common sites for atherosclerosis
Abdominal aorta followed by coronary arteries
Complications of atherosclerosis
Ischemic heart disease, abdominal aortic aneurysm, peripheral vascular disease (pain, pulselessness, paresthesia, claudication), TIA (vertebral basilar oclussion), renovascular hypertension (high renin).
Pathophysiology of essential hypertension
Retention of sodium and water with increase in stroke volume (systolic pressure). Sodium in smooth muscle opens up calcium channels with vasoconstriction of arterioles (increased diastolic pressure). Low renin hypertension.
Complications of hypertension
Concentric ventricular hypertrophy, AMI, hyaline arteriosclerosis, nephrosclerosis and CRF, intracranial bleeds, atherosclerosis
Renovascular hypertension
Atherosclerosis of renal artery orifice in males or fibromuscular hyperplasia in women. Severe hypertension, epigastric bruit. High renin hypertension. Screen with captopril.
Captopril screening test for renovascular hypertension
In renovascular hypertension there's decreased RPF and high levels of renin and angiotensin II. With captopril (ACE inhibitor), there's loss of negative feedback on renin and exagerated high levels of renin post-stimulation. The test has the potential for renal failure if bilateral renal artery stenosis is present as AII is responsible for maintaining renal blood flow.
Ahterosclerotic aneurysms
MC site is abdominal aorta below renal arteries (no vasa vasorum). Pulsatile mass with pain and abdominal bruit
Syphilitic aneurysm
Obliterative endarteritis of vasa vasorum with ischemia and atrophy of ascending aorta, aortic insuficiency, airway encroachment and laryngeal nerve involvment (brassy cough)
Associated diseases of dissecting aortic aneurysm
Marfan, Ehlers-Danlos, copper deficiency (no lysyl oxidase)
Signs and symptoms of dissecting aortic aneurysm
Acute retrosternal severe chest pain, aortic insuficiency and cardiac tamponade
Phlebothrombosis Vs. Thrombophlebitis
Phlebothrombosis is venous thrombosis of deep veins without inflamation or infection. Thrombophlebitis is venous thrombosis of superficial veins due to inflamation and infection
Signs, symptoms, diagnosis and complications of DVT
Leg swelling, warmth, erythema. Increased venous pressure from deep to superficial veins (which drain in deep veins) produces varicosities in superficial system. Complications are thromboembolism, thrombophlebitis. Dx.: Doppler
Signs, symptoms and causes of thrombophlebitis
Palpable cord, pain, induration, warmth, erythema. MCC is superficial varicose veins, phlebothrombosis, catherthers, drug abuse
Clinical features of varicose veins
Edema, thrombosis, stasis dermatitis, ulcerations
Clinical features of superior vena cava syndrome
Compression of SVN by primary lung cancer. Blue discoloration of the face, arms and shoulders, dizziness, convulsions, visual disturbances, distended jugular veins
Clinical features of Kaposi sarcoma
Malignant endothelial cell tumor caused by HHV-8. Multiple red-purple patches, plaques or nodules. Spindle shaped cells
Clinical features of stable angina
Chest pain induced by exercise or emotions. ST segment depression (subendocardial ischemia) Relieved by rest or nitroglycerin
Clinical features of Prinzmetal angina
Chest pain caused by coronary artery vasospasm. ST segment elevation. Relieved by nitroglycerin
Clinical features of unstable angina
Non-occlusive thrombus triggers release of TXA2 (vasoconstrictor). Occurs at rest. Risk of MI
Coronary irrigation of the heart
Left anterior descending artery supplies anterior portion of left ventricle and anterior 2/3 of interventricular septum (produces heart blocks) (45% of MI). Circumflex artery, branch of left coronary artery (15% of MI). Right coronary artery supplies posterior and inferior left ventricle, right ventricle, SA node (sinus bradycardia), papillary muscle (mitral insuficiency) (35% of MI)
Risk factors for coronary artery disease
Age, family history, cigarette smoke, hipertension, low HDL, high LDL, diabetes
Clinical presentation of AMI
Sudden onset of acute substernal chest pain radiated to left arm, jaw and neck. Shortness of breath, diaphoresis, nausea, vomiting and anxiety
Serum markers of miocardial infarction
CK-MB elevated by 8h, peaks 18h, normal in 3 days. Troponin elevated by 6h, peaks 16h, normal in 10 days. LDH elevted by 24h, peaks 6 days, normal in 14 days.
Gross changes in miocardial infarction
18h, no change. 24h vague pallor. 1-7d yellow pallor. 7-28d central pallor with red border. Months - white firm scar
Microscopic changes in miocardial infarction
4-24h coagulative necrosis. 1-3d neutrophilic infiltrate. 3-7d macrophages. 7-28d granulation tissue. Months - fibrotic scar
Complications of MI
Arrhythmias (MC COD), CHF, pericarditis, rupture (4-7 days post-infarct). Ventricular free wall (LAD) --> cardiac tamponade. Interventricular septum (LAD) --> left to right shunt. Papillary muscle (RCA) mitral insufficiency
Features of sudden cardiac death
Death within 1 hour of onset of symptoms by fatal arrhythmia. CAD (80%), hypertrophic cardiomyopathy, mitral valve prolapse, aortic stenosis
Pathophysiology of heart failure
Left ventricle fails --> decreased cardiac output --> RAA system and retention of Na and H20 --> increased venous return causes edema and partial compensation of CO. There's backward pulmonary congestion that causes dyspnea and pulmonary edema with decreased RV output that adds up to systemic edema. Increased sympathetic tone and volume retention are compensation mechanisms
Signs and symptoms of left heart failure
Dyspnea (due to increased pulmonary hydrostatic pressure), pillow orthopnea (no gravity increases venous return with pulmonary congestion), rales, S3 gallop (volume overloaded ventricle)
Complications of left heart failure
Pulmonary edema, excessive RAA leads to secondary hyperaldosteronism, cardiogenic shock
Features and treatment of systolic left heart failure
Due to decreased contractility after infarction. EF<0.4. Rx. Inotropics (digitalis), decrease afterload with vasodilators (ACE inhibitor)
Features and treatment of diastolic left heart failure
Due to decreased compliance of left ventricle (increases left atrial pressure and pulmonary congestion). EF>0.4. Due to left ventricular hypertrophy, restrictive cardiomyopathy. Rx.: increase preload by decreasing heart rate (calcium channel blockers and B-blockers)
Causes of right heart failure
Left heart failure (MCC), cor pulmonale (primary pulmonary hypertension)
Clinical features of right heart failure
Jugular venous distension, nutmeg liver hepatomegaly, dependant pitting edema, ascites, pleural effusions, tricuspid insuficiency
Causes and features of mitral stenosis
Chronic rheumatic fever is MCC. Mid-diastolic murmur. Dyspnea and hemoptisis (pulmonary congestion), atrial fibrillation (left atrial dilation), dysphagia for solids (enlarged left atrium compresses esophagus), hoarseness (irritation of recurrent laryngeal nerve)
Causes and features of mitral prolapse
Valve leaflets undergo myxomatous degeneration. Associated with lethal ventricular arrhythmias in Marfan. Mid-systolic click. Infectious endocarditis and rupture of chordae tendinae are complications Rx.: CCA, b-blockers and negative inotropic agents
Causes and features of mitral insuficiency
Caused by mitral prolapse, left heart failure, infective endocarditis, RCA thrombosis (papillary muscle). Holosystolic murmur heard best at apex, S3 heart sound.
Causes and features of aortic stenosis
MCC is calcified congenital bicuspid valve, rheumatic fever, old age. Decreased stroke volume and cardiac output, increased afterload. Left ventricular hypertrophy. Systolic ejection murmur. Associated with angina (less coronary filling), syncope (reduced cardiac output) and microangiopathic hemolytic anemia with schistocytes
Causes and features of aortic insuficiency
MCC is essential hypertension, infective endocarditis, syphilitic and aortic aneurysms. Left ventricular hypertrophy, increased preload. Diastolic murmur, bounding pulse.
Pathophysiology of rheumatic fever
Antibodies against streptococal M protein cross react with heart valves producing fibrosis/stenosis, as well as systemic features
Jones major criteria of rheumatic fever
Migratory polyarthritis, pancarditis, subcutaneous nodules, erythema marginatum, sydenhan chrorea
Pathognomonic lesion of rheumatic heart fever
Aschoff body. Fibrinoid necrosis surrounded by macrophages (Anitschkow cells), lymphocytes and plasma cells
Clinical features of subacute endocarditis
Strep viridans colonizes damaged valves. "FROM JANE". Fever, Roth spots on retina, Osler nodes (painful subcutaneous nodules on fingers and toes), murmur, Janeway lesions (painless red lesions on palms and soles), anemia, nailbed hemorrhage, septic emboli
Preductal coarctation of the aorta
Associated with Turner syndrome. Narrowing of aorta proximal to ductus arteriosus. Ususally associated with PDA that supplies oxygenated blood to distal aorta. Presents in newborn with CHF, weak pulses and cyanosis of lower extremities.
Postductal coarctation of the aorta
Narrowing of aorta distal to ductus arteriosus. Hypertension in upper extremities and hypotension in lower extremities. Can produce aortic insuficiency, berry aneurysms and secondat hypertension due to increased RAA (low renal flow)
Right to left shunts
Early cyanosis due to blood shunt past the lungs. Tetralogy of Fallot, transposition of great vessels, truncus arteriosus, tricuspid atresia.
Left to right shunts
Late cyanosis due to Eisenmenger syndrome. VSD, ASD, PDA
Eisenmenger syndrome
Right side of the heart hypertrophies due to a septal defect or PDA and shunt reverses from left-right to right-left producing cyanosis
Tetralogy of Fallot
Overriding aorta, pulmonic stenosis, right ventricular hypertrophy, VSD. Cyanosis depends on degree of pulmonic stenosis. PDA or ASD are cardioprotective.
Transposition of the great vessels
Inversion of aorta and pulmonary arteries. Infants of diabetic mothers. Must have ASD, VSD or PDA to survive.
Truncus arteriosus
Common pulmonary artery and aortic trunk. Massive blood flow to the lungs causes pulmonary hypertension. Early cyanosis and CHF.
Communication between ventricles. Large defect leads to pulmonary hypertension and Eisenmenger syndrome. Systolic murmur.
Communication between atriums. Associated with fetal alcohol syndrome.
Communication between aorta and pulmonary artery. Associated with congenital rubella. During pregnancy PDA is kept by PGE2. Close with indomethacin. Machinery murmur. Eisenmenger syndrome.
Dilated cardiomyopathy
Idiopathic, postpartum, alcohol, Coxackie B infections, doxorubicin and cocaine. Presents as CHF with decreased ejection fraction
Hypertrophic cardiomyopathy
Cause of death in young athletes. Autosomal dominant. Asymetrical hypertrophy in ventricular septum. Decreased compliance and stroke volume. Rx.: increase preload with beta blockers (decrease HR)
Carcinoid heart disease
Right sided endocardial and valvular fibrosis secondary to serotonin in patients with carcinoid metastasis to liver. Skin flushing, diarrhea, cramping, bronchospasm, wheezing, telangiectasia
Binds collagen, fibrin and integrins; adhesion glycoprotein of extracellular matrix; chemotactic for fibroblasts and endothelial cells
vascular endothelial growth factor; important in angiogenesis
Fibroblast growth factor; important in angiogenesis
Stimulates granulation tissue formation; stimulates proliferation of smooth muscle, fibroblasts and endothelium
Adhesion protein in basement membranes; binds type IV collagen, integrins and ECM components