674 terms

USMLE Pathology

Antithrombogenic substances

Prostacyclin (PGI2),
nitric oxide,
tissue plasminogen activator,
thrombomodulin

Steps in hemostasis

1. Endothelial injury relases tissue factor (activates factor VII, extrinsic pathway); exposure of thrombogenic subendothelial collagen activates factor XII (intrinsic pathway), release of vWF; decreased synthesis of antithrombogenic substances; 2. Platelet adhesion to vWF through glycoprotein Ib; 3. Platelet activation with degranulation and synhesis of TXA2 and ADP (aggregators); 4. Aggregation mediated by TXA2 and ADP and fibrinogen/Gp IIb-IIIa

Bernard Soulier syndrome

Autosomal recessive. Deficiency of platelet GPIb. Defective platelet adhesion

Glanzman thrombastenia

Deficiency of Gp IIB-IIIa; defective platelet aggregation

Immune thrombocytopenic pupura

Antiplatelet antibodies and destruction in spleen by macrophages (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

DIC

Thrombocytopenia, prolonged PT/PTT, decreased fibrinogen, elevated D-dimers

Hemophilia

Deficiency of factor VIII or IX. X-linked recessive (affects males). Bleeding at circumcision, hemarthrosis, easy bruising and hematomas. No petechiae or ecchymoses. Normal platelets and bleeding time, normal PT, prolonged PTT (intrinsic path coagulopathy)

Increased PT and PTT

Vitamin K deficiency, liver disease

Von Willenbrand disease

bleeding from 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

Firefighters

Carbon monoxide poisoning. Decreased SaO2, cherry red color of skin, headache. Rx.: 100% O2

Wood stoves and space heaters

Carbon monoxide poisoning. Decreased SaO2, cherry red color of skin, headache. Rx.: 100% O2

Pesticide industry

Organophosphate poisoning (acetylcholinesterase inhibitors) and arsenic. Lacrimation, salivation, miosis, weakness. Rx.: atropine

Meat packing industry

Plyvinyl chloride (PVC). Hepatic angiosarcoma

Coal workers

Anthracosis. Pulmonary fibrosis and respiratory distress

Insulation workers

Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain

Demolition workers

Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain

Construction workers

Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, brnchogenic CA, mesotheliomas, recurrent pleural effusions, dyspnea, pleuritic chest pain

Shipyard workers

Asbestosis. Interstitial lung fibrosis, fibrous pleural plaques, 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

Plumbers

Pottery paint

Combustion of polyurethane foam during fires

Cyanide poisoning. Blocks cytochrome oxidase. Hypoxia. Rx.: nitrites (form methhemoglobin which binds cyanide before it reaches tissues), thiosulfate bind cyanide forming thiocyanate

Dental amalgams

Mercury poisoning. Intention tremors, dementia, delirium

Insecticides

Mercury poisoning. Intention tremors, dementia, delirium

Hat-making industry

Mercury poisoning. Intention tremors, dementia, delirium

Cancers produced by cigarette smoke

Lung, oral cavitiy, pharynx, larynx, esophagus, pancreas, kidney

Cardiovascular disease due to cigarette smoke

Atherosclerosis (major risk factor), CAD, AMI, Buerger disease

Respiratory disease due to cigarette smoke

Chronic bronchitis, emphysema, asthma

Diseases associated with alcohol

Thiamine deficiency (Wernicke-Korsakoff), macrocytic anemia (folate deficiency), Mallory-Wiess, Boerhaave's syndrome, cirrhosis, esophageal varices, acute pancreatitis, congestive cardiomyopathy, hyperlipidemia

Down syndrome

Trisomy 21 due to meiotic nondisjunction (95%) or robertsonian translocation (4%); Severe mental retardation, mongoloid features, brushfeld spots, simian crease, heart defects, duodenal atresia, Hirchsprung, ALL, Alzheimer's by age 40

Edward syndrome

Trisomy 18. Mental retardation, low set ears, micrognathia, heart defects, overlapping flexed fingers, rocker-bottom feet

Patau syndrome

Trisomy 13. Mental retardation, cleft lip or palate, cardiac defects, renal defects, microcephaly, polydactyly

Cri du chat

5p deletion. Cat-like cry, mental retardation, heart defects, microcephaly

Klinefelter syndrome

47XXY. Male hypogonadism, testicular atrophy, infertility, female distribution of hair, gynecomastia, elevated 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

PKU

Deficiency of phenylalanine hydroxylase. Mental retardation by 6 months, light-colored hair and skin, musty odor. Avoid aspartame, monitor pregnancy

Alkaptonuria

"Black Homo" homogentisic acid oxidase deficiency. Black urine, black cartilage

Albinism

Tyrosinase deficiency. Increased risk of squamous carcinoma, no melanin

Von Gierke disease

Glucose 6 phosphatase deficiency. Hepatomegaly, fasting hypoglycemia, hyperuricemia

Pompe disease

Lysosomal alpha 1-4 glucosidase deficiency. Hepatomegaly, muscle hypotonia, cardiomegaly

McArdle disease

Myophosphorylase deficiency. Excersice-induced muscle cramps

Tay SaX

Hexosaminidase A deficiency with acumulation of glangliocerebroside GM2. Mutation of HEXA gene on chromoseme 15. Cherry-red spot on retina

Nieman PickS

Sphingomyelinase deficiency. Cherry-red spot on retina, hepatosplenomegaly, zebra bodie on EM

Gaucher disease

Glucocerebrosidase deficiency. In adulthood, hepatosplnomegaly, hypersplenism, lymphadenopathy, osteoporosis

Mucopolysaccharidosis

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

Ehlers-Danlos

Hyperxtensible skin and joints. Collagen gene defects

Menkes disease

Mutation in Cu+ efflux protein gene. High concentration of Cu+ that cant be released. Associated with Ehlers-Danlos type 9

Neurofibromatosis type 1

Von Recklinghousen disease (has 17 letters). NF-1 tumor suppressor gene mutation on chromosome 17. Normal gene product neurofibromim inhibits p21 ras oncoprotein. Neurofibromas, café-au-lait spots, Lisch nodules (pigmented iris hamartomas)

Neurofibromatosis type 2

NF-2 tumor suppressor gene mutation on chromosome 22. Bilateral acoustic neuromas, café-au-lait spots, pheochromocytoma

Von Hippel Lindau disease

Mutation on VPL tumor suppressor gene on chromosome 3p. Retinal hemangioblastoma, hemangioblastoma of cerebellum, brainstem and spinal cord, cysts of the liver, pancreas and kidneys, bilateral renal carcinomas

Fragile X syndrome

X-linked dominant mutations on FMR-1 gene. CGG triplet repeats. Retardation elongated face with large jaws, large everted ears, macroorchidism

Huntington disease

CAG triplet repeats of huntington gene produces neurotoxic protein. Progressive dementia, choreiform movements

Prader-Willi syndrome

Deletion of paternal 15q. Mental retardation, obesity, hypogonadism, hypotonia

Angelman syndrome

deletion of maternal 15q. Retardation, seizures, ataxia, inapropriate happy-puppet laughter

Homocystinuria

Cysthathione synthase deficiency. Resembles Marfan. Ectopic lens, arachnodactyly, eunuchoid proportions osteoporosis, atherosclerosis, DVT

Classic 21B-Ohase deficiency

Hypovolemia, hyponatremia, female pseudohermaphrodite, hirsutism (increased 17 KS), skin hyperpigmentation (high ACTH increases melanin). Labs: increased serum 17OH-progesterone, hyperkalemia, metabolic acidosis, increased 17KS, decreased 17OHCS, hypocortisolism

Non-classic 21B-Ohase deficiency

Increase in 17 KS, hirsutism, no salt loss, acne in females, secondary amenorrhea. Labs: increased 17OH pregenterone

Classic 11OHase deficiency

Salt retention/hypertension (11-deoxycorticosterone), increased 17KS (virilization), skin hyperpigmentation

17OHase deficiency

Salt retention, hypertension, (aldosterone), female hypogonadism (decreased 17KS), male pseudohermaphrodite (low 17KS). Labs: low 17KS, 17OHCS, hypocortisolism, increased ACTH

Clinical features of SLE

Type II and III hypersensitivity reactions. Pancytopenia, arthritis, butterfly rash, diffuse proliferative glomerulonephritis, Libman-Sacks endocarditis. ANA, anti-DNA, anti-Sm, anti-histone (drug-induced lupus). Rx.: steroids

Sjogren syndrome

Autoantibodies against lacrimal and salivary glands. Keratoconjunctivitis, corneal ulcers (dry eyes), xerostomia (dry mouth). Anti-Ro (SS-A), anti-La (SS-B). 15% of rheumatoid arthritis patients have Sjogren.

Mikulicz syndrome

Enlargement of the salivary and lacrimal glands associated with Sjogren syndrome

Diffuse scleroderma

Fibroblast stimulation and deposition of collagen in the skin and internal organs. Anti-DNA topoisomarease I (Scl-70) (helicase). Skin involvement, dysphagia, malabsorption, pulmonary fibrosis (dyspnea), cardiac fibrosis (arrhythmias), kidney fibrosis (renal failure)

Localized scleroderma (CREST)

Fibroblast stimulation and deposition of collagen. Anti-centromere antibodies. Calcinosis, Raynaud, esophageal dysmoility, sclerodactyly, telangiectasia.

Bruton's agammaglobulinemia

X-linked recessive. No B cells, No Igs. Recurrent staph, haemophilus and strep infections after 6 months. Increased pre-B cells. Mutation of B-cell Bruton tyrosine kinase (btK).

Common variable immunodeficiency

B-cell maturation defect. Hypogammaglubulinemia, recurrent bacterial infections, giardia lamblia.

DiGeorge syndrome

Failure to develop 3rd and 4th pharyngeal puches results in absence of parathyroid and thymus glands, hypocalcemia, tetany, T-cell deficiency, recurrent viral infections, heart defects, chronic candidiasis

SCID

B and T cell deficiency due to mutation of IL-2 receptor (x-linked), adenosine deaminase deficiency (AR) or failure to make MHC II. Recurrent infections and susceptibility to candida, CMV and p. carinii

Wiskot-Aldrich syndrome

X-linked recessive. "WIPE": recurrent infections, thrombocytopenic purpura, eczema, risk of lymphomas, low IgM

Ataxia-Telangiectasia

Ataxia, spider angiomas, low IgA, defect of DNA repair enzyme

Chronic granulomatous disease

Low NADPH oxidase. Recurrent catalase+ infections, negative nitroblue tetrazolium test.

Leukocyte adhesion deficiency

Defect of CD-18 (LFA-1 beta chain), no pus formation, failure of umbilical cord to detach

Chediak-Higashi

Defect in microtubules with no phagocytosis by lysosome. Partial albinism, peripheral neuropahty, recurrent infections

Hereditary angioedema

Edema at mucosal surfaces. Defect of C1-INH (esterase inhibitor). Decreased C1, C2, C4

Hyper IgM

Defect of CD-40L on T-lymphocytes. No 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

Opsonins

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

CGD

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

Anaphilotoxins

C3a, C5a. Directly stimulate histamine release from basophils, mast cells and platelets

C3b

Opsonin; neutrophils, macrophages and monocytes have C3b receptros

Bradikinin synthesis and actions

Synthesized from activation of prekalikrein by factor XII (Hageman). Kalikrein cleaves HMWK into bradikinin. Vasodilator, increased permeability, brnchoconstrictor, pain

PGE2

Vasodilation in kidneys, increases renal blood flow, increases gastric mucosal blood flow (mucoprotection), activates osteoclasts, fever, pain, maintains ductus arteriosus

Prostacyclin (PGI2)

Vasodilation and inhibits platelet aggregation

IL-1

Stimulates PGE2 synthesis in hypothalamus --> fever; B-cell stimulation to synthesize Ig; osteoclast activation (released by osteoblasts under PTH stimulation); lytic bone lessions of multiple myeloma; increases adhesion molecules in endothelium; increases acute phase reactants

Hageman factor

Activates intrinsic coagulation system, kinin cascade and fibrinolytic system

PGF

Uterine muscle contraction (cause pf primary amenorrhea)

gamma interferon

Produced by CD4 TH1 cells and NK cells. Activates macrophages; antiviral properties; class I and class II antigens; increases IL-2, IL-12 production by CD4 cells

IL-2

Produced by CD4 cells. T cell growth factor. Promotes B cell and NK cell proliferation

IL-6

Synthesis of acute phase reactants

Factors that increase adhesion molecule synthesis

C5a, LTB4, IL-1, TNF

Key cells in acute and chronic inflamation

Acute: neutrophil has IgG and C3b receptros; Chronic: macrophage has receptors for IgG and C3b, process antigen and secrete IL-1, IL-12 and TNF

Chronic granulomatous inflamation

Epitheloid cells and multinucleated giant cells surrounded by a rim of lymphocytes with central caseous necrosis

Type I collagen

skin, bones, tendons and most organs

Type II collagen

Cartilage and vitreous humor

Type III collagen

granulation tissue

Type IV collagen

basement membranes

Composition of basement membranes

Has negative charge. Collagen type IV, proteoglycans (heparan sulfate), laminin, fibronectin

Nitrosamines

Gastric CA, Esophagus

Cigarette smoke

Larynx, ling, renal cell carcinoma, transitional cell carcinoma

Polycyclic aromatic hydrocarbons

Bronchogenic CA

Asbestos

Bronchogenic CA, mesothelioma

Chromium and nickel

Bronchogenic CA

Arsenic

Squamous cell CA of skin and lung, angiosarcoma of liver

Vinyl chloride (PVC)

Liver angiosarcoma

Alkylating agents

Leukemia, lymphoma

Benzene

Leukemia, lymphoma

Napthalene

Bladder CA

CCL4

Liver centrilobular necrosis

HTLV-1

Adult T-cell leukemia

HBV, HCV

Hepatocellular CA

EBV

Burkitt's lymphoma, nasopharyngeal CA

HPV

Cervical CA (16, 18)

HHV-8

Kaposi sarcoma

hst-1 & int-2

Cancer of stomach, breast, bladder and melanoma; produces growth factors; overexpression

sis

Astrocytoma; produces PDGF; overexpression

erb-B1

SCC of lung; produces EGF receptor; overexpression

erb-B2

Breast, ovary and lung CA; produces EGF receptor; amplification

erb-B3

Breast; produces EGF receptor; overexpression

ret

MEN II & III, medullary thyroid CA; produces glial neurotrophic factor receptor; Point mutation

abl

CML, ALL; produces signal transduction proteins; translocation t(9:22), Philadelhpia chromosome

Ki-ras

Lung, pancreas and colon; produces GTP binding proteins; Point mutation

c-myc

Burkitt lymphoma; produces nuclear regulatory protein; translocation t(8:14). When associated to p53 apoptosis; when associated to bcl-2 inhibits apoptosis

L-myc

Small cell lung CA; produces nuclear regulatory protein; amplification

N-myc

Neuroblastoma; produces nuclear regulatory protein; amplification

bcl-1

Mantle cell lymphoma; produces cyclin D protein; translocation t(11:14)

CDK4

Melanoma; produces cdk; amplification

bcl-2

Normally prevents apoptosis. Follicular and undiferentiated lymphomas t(14:18). Chromosome 14: Ig heavy chain; chromosome 18 bcl-2

c-kit

gastrointestinal stromal tumor

p53

Normally prevents a cell with damaged DNA from entering S-phase by inhibiting cyclin/cdk. Colon, breast, CNS, lung. On chromosome 17

Normally prevents a cell from entering S phase. Retinoblastoma, osteogenic sarcoma. Inactivated product by cyclin/cdk. On chromosome 13

Alpha fetoprotein

Hepatocellular CA, testicular tumors

B-hCG

Trophoblastic tumors, chroriocarcinoma

Calcitonin

Medullary CA of thyroid

CEA

lung, pancreas, stomach, breast, colon

CA-125

Ovarian CA

CA19-9

Pancreatic CA

Placental alkaline phosphatase

Seminoma

Prostatic acid phosphatase

Prostate CA

PSA

Prostate CA

Alkaline phosphatase

Metastasis to bone, primary billiary cirrhosis

VHL

Chr 3p. Von Hippel Lindau, renal cell CA

WT-1, WT-2

11p. Wilm tumor

BRCA-1

17q. Hereditary breast and ovarian CA

BRCA-2

13q. Hereditary breast CA

APC

5q. Adenomatous polyps and colon CA

DCC

18q. Colon CA

NF-1

17q. Neurofibromatosis

NF-2

22q. Acoustic neuromas and meningiomas

Down Syndrome

ALL, AML

Xeroderma pigmentosum, albinism

Squamous cell, basal cell CA, melanoma

Chronic atrophic gastritis, pernicious anemia, H. pylory

Gastric adenocarcinoma

Tuberous sclerosis

Astrocytoma; produces PDGF; overexpression

Actinic keratosis

Squamous cell CA of skin and lung, angiosarcoma of liver

Barret's esophagus

Esophageal adenocarcinoma

Plummer-Vinson syndrome

Iron deficiency causes atrophic glositis, esophageal webs, anemia, squamous cell CA of esophagus

Cirrhosis

Hepatocellular CA

Ulcerative colitis

Colonic adenocarcinoma

Paget's

Osteosarcoma

Immunodeficiency

Malignant lymphomas

AIDS

Non-Hodgkin's, Kaposi

Dysplastic nevus

Malignant melanoma

Radiation

Sarcoma

Small cell lung CA paraneoplastic syndromes

Cushing's (ACTH), SIADH (ADH)

Squamous cell lung CA paraneoplastic syndrome

Hypercalcemia (PTH-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)

alpha1-antitrypsin

Hepatocellular CA

Bence Jones protein

Multiple Myeloma (Ig light chains in urine)

MEN-I

Pituitary (ACTH, Cushings), parathyroid (hypercalcemia), pancreas (zollinger-ellison, insulinoma)

MEN-II

medullary thyroid CA, parathyroid adenoma (hypercalcemia), pheocromocytoma (hypertension)

5 leading causes of death in US

1. Heart disease; 2. Cancer; 3. Cerebrovascular disease; 4. COPD; 5. Accidents

3 leading causes of death in children in US

1. Accidents; 2. Cancer; 3. Congenital abnormalities

3 most common cancers in males

1. Prostate; 2. Lung and bronchus; 3. Colon/rectum

3 most common cancers in females

1. Breast; 2. Lung; 3. Colon/rectum

Top 3 cancer mortality in males

1. Lung; 2. Prostate; 3. Colon/rectum

Top 3 cancer mortality in females

1. Lung; 2. Breast; 3. Colon/rectum

5 causes of tissue hypoxia

ischemia, hypoxemia, ETC block, uncoupled ETC, AV shunts

Ultimate effects of tissue hypoxia

No O2 to accept electrons in ETC, no production of ATP. Na/K pump fails and cell swells (reversible change). Ribosomes fall from RER. Disruption of cell membrane and mitochondria induces apoptosis.

Effects of low ATP in cell

Increased glycolysis to support ATPase pump. Anaerobic glycolysis produces lactate with decreased intracellular pH which denatures proteins (coagulation necrosis), cell swelling, entry of calcium and apoptosis

Pathophysiology of cell injury in hypoxia

ETC fails due to lack of oxygen; 2. No ATP production in ETC increases anaerobic glycolysis (high citrate and AMP activate PFK-1); 3. increased lactate decreases cell pH which denatures proteins and produces coagulation necrosis; 4. ATPase fails and cell swells with fall off of ribosomes from RER; 5. disruption of cell membrane with entry of Ca activates 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

Anemia

Normal Hb, PaO2, decreased SaO2, decreased O2 content

CO poisoning or methhemoglobinemia

CO poisoning tissue hypoxia

Decreased O2 content and SaO2, normal PaO2, left shift of dissociation curve and cytochrome oxidase inhibition all cause hypoxia. Produced by car exhaust, heaters, smoke inhalation, wood stoves. Rx.: 100% O2. First symptom: headache

Factors that left-shift O2 dissociation curve and decrease P50

Decreased 2,3BPG, CO, MetHb, HbF, hypothermia, alkalosis

Factors that right-shift O2 dissociation curve and increase P50

Increased 2,3BPG, fever, acidosis

Causes of hypoxia with normal O2 content

Ischemia, cyanide poisoning, ETC uncouplers (alcohol, salicylates, dinitrophenol)

Free radical metabolism

NADPH oxidase and spontaneous superoxide, Superoxide dismutase makes H2O2 from superoxide. Catalase breaks down H2O2. Gluthathione reductase and GSH peroxide breakdwon 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

Meningocele

Bony defect with outpuching of the meninges

Meningomyelocele

Defective bony arch with outpuching of meninges, spinal cord and spinal roots. May lead to paraplegia and urinary incontinence

Myelocele

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)

Cretinism

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

Hypoparathyroidism

Due to surgical removal of glands or DiGeorge syndrome. Hypocalcemia with low PTH, tetany, prolonged QT interval

Prolactinoma

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.

SIADH

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

Pheochromocytoma

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.

MEN I

Tumors of the pituitary (non-functioning), parathyroids (hypercalcemia), and pancreas gastrinoma (zollinger-ellison)

MEN II

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

Volvulus

Twisting of bowelon its vascular mesentery resulting in obstruction and infarction

Intussusception

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.

Appendicitis

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

HNPCC

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

Insulinoma

Produces insulin. Hypoglycemia, elevated insulin and C-peptide. Rx.: glucose

Gastrinoma

Produces gastrin. Zollinger-Ellison: high gastrin, high gastric acid, intractable peptic ulcers

Somatostinoma

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.

Cirrhosis

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.

Hemochromatosis

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.

Budd-Chiari

Hepatic vein thrombosis caused by polycythemia, contraceptives, pregnancy. Abdominal pain, hepatomegaly, ascites.

HCC

Due to cirrhosis, HBV, HCV, alcohol, hemochromatosis. Tumor marker - alpha-fetoprotein.

Target cells

increased RBC membrane. Hemoglobinopathies, thalassemia, liver disease.

Acanthocytes

Irregular spicules on surface. Abetalipoproteinemia

Spherocytes

Decreased RBC membrane. No central area of pallor. Spherocytosis

Schistocytes

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

Reticulocytes

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

AOCD

High serum iron, serum ferritin and % saturation with low TIBC

Sideroblastic anemia

AOCD

Iron is trapped in bone marrow macrophages due to high levels of IL-1 and lactoferrin. High ferritin and low TIBC.

HbA

α2β2

HbF

α2γ2

Hb Barts

γ4

HbH

β4

α-thalassemia

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

β-thalassemia

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

HbA2

α2δ2

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

Cytomegalovirus

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

Pre-B ALL

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)

AML

15-60 years. Myeloblast proliferation. Auer rods are pathognomonic of myeloblasts. T(15;17). Abnormal retinoic acid receptor. Rx.: retinoic acid

CML

15-60 years. Pluripotent cell proliferation. Philadelphia chromosome t(9;22). All cells increased with low LAP

PRV

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).

t(15;17)

AML translocation

t(9;22)

CML philadelphia chromosome translocation. Forms a protein with tyrosine kinase activity

t(14;18)

Follicular B-cell lymphoma translocation

t(8;14)

Burkitt's lymphoma translocation

Composition of bone

Organic matrix: osteoblasts, osteoclasts, type I collagen, glycoproteins. Inorganic matrix: calcium hydroxyapatite, magnesium, potassium, chloride, sodium

Osteoblasts

Production of unmineralized bone. High amounts of alkaline phosphatase and PTH receptors to modulate osteoclasts

Osteoclasts

Bone resorption

Achodroplasia

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

Staph

Osteomyelitis in sickle cell disease

Salmonella

Osteomyelitis in drug abusers and diabetics

Pseudomonas

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

Vitiligo

Irregular, completely depigmented patches devoid of melanocytes.

Melasma

Irregular blotchy patches of hyperpigmentation on the face

Freckles

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

Psoriasis

Well demarcated erythematous plaque with a silvery scale. Epidermal hyperplasia (acanthosis), patchy keratinization with parakeratosis. Rx.: topical steroids and radiation

Pemphigus

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

Endometriosis

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)

Choriocarcinoma

Malignant germ cell tumor derived from the trophoblast

Fibrocystic change presentation

Bilateral painful mass in young woman with menstrual variation

Fibroadenoma

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

c-anca

Treatment of Wegner granulomatosis

cyclophosphimide

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.

VSD

Communication between ventricles. Large defect leads to pulmonary hypertension and Eisenmenger syndrome. Systolic murmur.

ASD

Communication between atriums. Associated with fetal alcohol syndrome.

PDA

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

Fibronectin

Binds collagen, fibrin and integrins; adhesion glycoprotein of extracellular matrix; chemotactic for fibroblasts and endothelial cells

VEGF

vascular endothelial growth factor; important in angiogenesis

FGF

Fibroblast growth factor; important in angiogenesis

PDGF

Stimulates granulation tissue formation; stimulates proliferation of smooth muscle, fibroblasts and endothelium

Laminin

Adhesion protein in basement membranes; binds type IV collagen, integrins and ECM components

USMLE Pathology

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