High Yield

High Yield General Pathology

All the high yield facts from general pathology that are usually asked in examsUSMLE STEP 1, Medical Council exams.

Reversible Cell Injury

• swelling of cell organelles and entire cell

• dissociation of ribosomes from endoplasmic reticulum

• decreased energy production by mitochondria

• increased glycolysis → decreased pH → nuclear chromatin clumping

Irreversible Cell Injury

• dense bodies within mitochondria (flocculent densities in heart)

• release of cellular enzymes (e.g., SGOT, LDH, and CPK after MI)

• nuclear degeneration (pyknosis, karyolysis, karyorrhexis)

• cell death

Irreversible Cell Injury

• dense bodies within mitochondria (flocculent densities in heart)

• release of cellular enzymes (e.g., SGOT, LDH, and CPK after MI)

• nuclear degeneration (pyknosis, karyolysis, karyorrhexis)

• cell death

FATTY CHANGE OF THE LIVER

1. Increased delivery of free fatty acids to liver

• starvation

• corticosteroids

• diabetes mellitus

2. Increased formation of triglycerides

• alcohol (note: NADH > NAD)

3. Decreased formation of apoproteins

• carbon tetrachloride

• protein malnutrition (kwashiorkor)

Apoptosis

• “programmed” cell death

• single cells (not large groups of cells)

• cells shrink → form apoptotic bodies

• gene activation → forms endonucleases

• peripheral condensation of chromatin with DNA ladder

• no inflammatory response

Examples of apoptosis:

1. Physiologic

• involution of thymus

• cell death within germinal centers of lymph nodes

• fragmentation of endometrium during menses

• lactating breast during weaning

2. Pathologic

• viral hepatitis

• cytotoxic T cell–mediated immune destruction (type IV hypersensitivity)

Necrosis

• cause → hypoxia or toxins (irreversible injury)

• many cells or clusters of cells

• cells swell

• inflammation present

Examples of necrosis:

• coagulative necrosis → ischemia (except the brain)

• liquefactive necrosis → bacterial infection (and brain infarction)

• fat necrosis → pancreatitis and trauma to the breast

• caseous necrosis → tuberculosis

• fibrinoid necrosis →autoimmune disease (type III hypersensitivity reaction)

• gangrene →ischemia to extremities →dry (mainly coagulative necrosis)

or wet (mainly liquefactive necrosis due to bacterial infection)

Adaptation

• hypertrophy → increase in the size of cells

• hyperplasia → increase in the number of cells

• atrophy → decrease in the size of an organ

• aplasia → failure of cell production

• hypoplasia → decrease in the number of cells

• metaplasia → replacement of one cell type by another

• dysplasia → abnormal cell growth

Abnormal Organ Development

• agenesis → complete failure of an organ to develop (no anlage present)

• hypoplasia → reduction in the size of an organ due to a decrease in the

number of cells

• atrophy →decrease in the size of an organ due to a decrease in the number

of preexisting cells

CARDINAL SIGNS OF INFLAMMATION

• rubor → red

• calor → hot

• tumor → swollen

• dolor → pain

COMPLEMENT CASCADE

• C3b → opsonin

• C5a → chemotaxis and leukocyte activation

• C3a, C4a, C5a → anaphylatoxins

• C5–9 → membrane attack complex

Deficiencies

• deficiency of C3 and C5 → recurrent pyogenic bacterial infections

• deficiency of C6, C7, and C8 →recurrent infections with Neisseria species

• deficiency of C1 esterase inhibitor → hereditary angioedema

• deficiency of decay-accelerating factor → paroxysmal nocturnal hemoglobinuria

THROMBOXANE VS. PROSTACYCLIN

Thromboxane

• produced by platelets

• causes vasoconstriction

• stimulates platelet aggregation

Prostacyclin

• produced by endothelial cells

• causes vasodilation

• inhibits platelet aggregation

GRANULOMATOUS INFLAMMATION

Caseating Granulomas

• aggregates of activated macrophages (epitheloid cells)

• tuberculosis

Noncaseating Granulomas

• sarcoidosis

• fungal infections

• foreign-body reaction

COLLAGEN TYPES

Fibrillar Collagens

• type I → skin, bones, tendons, mature scars

• type II → cartilage

• type III → embryonic tissue, blood vessels, pliable organs, immature

scars

Amorphous Collagens

• type IV → basement membranes

• type VI → connective tissue

Exudates

1. Composition

• increased protein

• increased cells

• specific gravity greater than 1.020

2. Cause

• inflammation

• increased blood vessel permeability

Transudates

1. Composition

• no increased protein

• no increased cells

• specific gravity less than 1.012

2. Cause → abnormality of Starling forces

a. increased hydrostatic (venous) pressure

• congestive heart failure

• portal hypertension

b. decreased oncotic pressure → due to decreased albumin

• liver disease

• renal disease (nephrotic syndrome)

c. lymphatic obstruction

• tumors or surgery

• filaria

NEOPLASMS

Benign

• grow slowly

• remain localized

• may have well-developed fibrous capsule

• do not metastasize

• well differentiated histologically

Malignant

• grow rapidly

• locally invasive

• irregular growth; no capsule

• capable of metastasis

• variable degrees of differentiation (well differentiated, moderately differentiated,

poorly differentiated)

ONCOGENE EXPRESSION

Growth Factors

1. c-sis

• β chain of platelet-derived growth factor

• astrocytomas and osteogenic sarcomas

 

Growth Factor Receptors

1. c-erb B1

• receptor for epidermal growth factor

• breast cancer and squamous cell carcinoma of the lung

2. c-neu

• receptor for epidermal growth factor

• breast cancer

3. c-fms

• receptor for colony-stimulating factor (CSF)

• leukemia

 

Abnormal Membrane Protein Kinase

1. c-abl

• membrane tyrosine kinase

• chronic myelocytic leukemia (CML)

 

GTP-Binding Proteins

1. c-ras

• product is p21 (protein)

• adenocarcinomas

 

Nuclear Regulatory Proteins

1. c-myc → Burkitt’s lymphoma

2. N-myc → neuroblastoma

3. L-myc → small cell carcinoma of the lung

4. c-jun

5. c-fos

CHROMOSOMES AND CANCER

Point Mutations

• c-ras → adenocarcinomas

 

Translocations

• c-abl on chromosome 9 → CML

• c-myc on chromosome 8 → Burkitt’s lymphoma

• bcl-2 on chromosome 18 → nodular lymphoma

 

Gene Amplification

• N-myc → neuroblastoma

• c-neu → breast cancer

• c-erb B2 → breast cancer

ANTIONCOGENES

Tumor Suppressor Genes

• Rb → retinoblastoma and osteogenic sarcoma

• p53 → many tumors and the Li-Fraumeni syndrome

• WT1 → Wilms’ tumor and aniridia

• NF1 → neurofibromatosis type 1

CHEMICAL CARCINOGENS

Initiators

• tobacco smoke → many tumors

• benzene → leukemias

• vinyl chloride → angiosarcomas of the liver

• β-naphthylamine → cancer of the urinary bladder

• azo dyes → tumors of the liver

• aflatoxin → hepatoma

• asbestos → mesotheliomas and lung tumors

• arsenic → skin cancer

Promoters

• saccharin → bladder cancer in rats

• hormones (estrogen)

VIRUSES AND CANCER

RNA Viruses

• acute-transforming viruses

• slow-transforming viruses

• HTLV-1 → adult T cell leukemia/lymphoma

 

DNA Viruses

1. HPV (different subtypes)

• cervical neoplasia

• condyloma

• verruca vulgaris

2. EBV

• African Burkitt’s lymphoma

• carcinoma of the nasopharynx

• B cell immunoblastic lymphoma

3. Hepatitis B and hepatitis C

• liver cancer

PARANEOPLASTIC SYNDROMES

• Cushing’s syndrome (increased cortisol) → lung cancer

• carcinoid syndrome (increased serotonin) → lung cancer or carcinoid

tumor of the small intestine

• syndrome of inappropriate ADH secretion (SIADH) → lung cancer and

intracranial neoplasms

• hypercalcemia → lung cancer or multiple myeloma

• hypocalcemia → medullary carcinoma of the thyroid (secretes procalcitonin;

stains as amyloid)

• hypoglycemia → liver cancer and tumors of the mesothelium (mesotheliomas)

• polycythemia (erythropoietin) →kidney tumors, liver tumors, and cerebellar

vascular tumors

TUMOR MARKERS

b-HCG (Human Chorionic Gonadodotropin)

• gestational trophoblastic disease (e.g., choriocarcinoma, hydatidiform mole)

• dysgerminoma

• seminoma (10% of cases)

a-Fetoprotein (AFP)

• liver cancer

• germ cell tumors (e.g., yolk sac tumors, embryonal carcinoma, NOT seminoma)

Prostate-Specific Antigen (PSA) and Prostatic Acid

Phosphatase (PAP)

• adenocarcinoma of prostate

Carcinoembryonic Antigen (CEA)

• adenocarcinomas of colon, pancreas, stomach, and breast (nonspecific marker)

CA-125

• ovarian cancer

S-100

• melanoma

• neural tumors

PROTEIN-ENERGY MALNUTRITION (PEM)

Kwashiorkor

• dietary protein deficiency (without calorie deficiency)

• anasarca (generalized edema)

• fatty liver (due to decreased apoproteins and decreased VLDL synthesis)

• abnormal skin and hair

• defective enzyme formation → malabsorption (hard to treat)

Marasmus

• dietary calorie deficiency (without protein deficiency)

• generalized wasting (“skin and bones”)

NUTRITIONAL DEFICIENCIES

Vitamin A

• night blindness

• dry eyes and dry skin

• recurrent infections

Vitamin D

• decreased calcium

• bone → decreased calcification, increased osteoid

• children → rickets

• adults → osteomalacia

Vitamin E

• degeneration of posterior columns of spinal cord

Vitamin K

• decreased vitamin K–dependent factors → II, VII, IX, X, and proteins C

and S

• increased bleeding

• increased PT and PTT

Vitamin B1 (Thiamine)

• beriberi → wet (cardiac) or dry (neurologic)

• Wernicke-Korsakoff syndrome (lesions of mamillary bodies)

Vitamin B3 (Niacin)

• pellagra → 3Ds = dermatitis, dementia, diarrhea (and death)

Vitamin B12 (Cobalamin)

• megaloblastic (macrocytic) anemia

• hypersegmented neutrophils (> 5 lobes)

• subacute combined degeneration of the spinal cord

Vitamin C (Ascorbic Acid)

• scurvy

• defective collagen formation → poor wound healing (wounds reopen)

• bone → decreased osteoid

• perifollicular hemorrhages (“corkscrew” hair)

• bleeding gums and loose teeth

Folate

• megaloblastic (macrocytic) anemia

• hypersegmented neutrophils

• associated with neural tube defects in utero

Iron

• microcytic hypochromic anemia (with increased TIBC)

INHERITANCE PATTERNS

Autosomal Dominant (AD)

• disease produced in heterozygous state

• no skipped generations → parents affected (unless new mutation or reduced penetrance)

• father-to-son transmission possible

• males and females affected equally

• recurrence risk is 50%

Autosomal Recessive (AR)

• disease produced in homozygous state

• heterozygous individuals are carriers

• skipped generations

• father-to-son transmission possible

• males and females affected equally

• recurrence risk is 25%

X-Linked Dominant (XD)

• no skipped generations

• no male-to-male transmission

• females affected twice as often as males

X-Linked Recessive (XR)

• skipped generations

• no male-to-male transmission

• males affected more frequently than females

Y Inheritance

• only males affected

• only male-to-male transmission

• all males affected

Mitochondrial

• males and females affected

• only females transmit the disease

EXAMPLES OF XR

Hematology Diseases

• glucose-6-phosphate dehydrogenase (G6PD) deficiency

• hemophilia A (deficiency of factor VIII)

• hemophilia B (deficiency of factor IX)

Immunodeficiency Diseases

• Bruton’s agammaglobulinemia

• chronic granulomatous disease

• Wiskott-Aldrich syndrome

Storage Diseases

• Fabry’s disease

• Hunter’s syndrome

Muscle Diseases

1. Duchenne muscular dystrophy

• defective dystrophin gene (muscle breakdown)

• pseudohypertrophy of calf muscles

• Gower maneuver (using hands to rise from floor)

2. Becker muscular dystrophy

Metabolic Diseases

• diabetes insipidus

• Lesch-Nyhan syndrome

Other Diseases

• red-green color blindness

• fragile X syndrome

AUTOSOMAL TRISOMIES

Trisomy 13 (Patau’s Syndrome)

• mental retardation

• microcephaly and microphthalmia

• holoprosencephaly (fused forebrain)

• fused central face (“cyclops”)

• cleft lip and palate

• heart defects

Trisomy 18 (Edwards’ Syndrome)

• mental retardation

• micrognathia

• heart defects

• rocker-bottom feet

• clenched fist with overlapping fingers

Trisomy 21 (Down’s Syndrome)

• most cases due to maternal nondisjunction during meiosis I (associated

with increased maternal age)

• minority of cases due to Robertsonian (balanced) translocation

• mental retardation (most common familial cause)

• oblique palpebral fissures with epicanthal folds

• horizontal palmar crease

• heart defects (endocardial cushion defect is most common)

• acute lymphoblastic leukemia (first 2 years of life)

• Alzheimer’s disease (almost 100% incidence after age 35)

• duodenal atresia (“double-bubble” sign on x-ray)

CHROMOSOMAL DELETIONS

5p- (Cri du Chat)

• high-pitched cry

• mental retardation

• heart defects and microcephaly

11p-

• Wilms tumor

• absence of iris

13q-

• retinoblastoma

15q-

1. Maternal deletion → Angelman’s syndrome

• stiff, ataxic gait with jerky movements

• inappropriate laughter (“happy puppets”)

• may be due to two copies of paternal 15 chromosome (paternal uniparental

disomy)

2. Paternal deletion → Prader-Willi syndrome

• mental retardation

• short stature and obesity

• small hands and feet

• hypogonadism

• may be due to two copies of maternal 15 chromosome (paternal uniparental

disomy)

HYPOGONADISM

Klinefelter’s Syndrome

• most common genotype is 47,XXY

• male hypogonadism

• testicular dysgenesis → small, firm, atrophic testes

• decreased testosterone

• increased FSH, LH, estradiol

• decreased secondary male characteristics

• tallness, gynecomastia, and female distribution of hair

• infertility

Turner’s Syndrome

• most common genotype is 45,XO

• female hypogonadism

• ovarian dysgenesis → streak ovaries

• decreased estrogen

• increased LH, FSH

• primary amenorrhea

• decreased secondary female characteristics

• skeletal abnormalities → short stature

• web neck (cystic hygroma)

AMBIGUOUS SEXUAL DEVELOPMENT

True Hermaphrodite

• ovaries and testes both present

Female Pseudohermaphrodite (XX Individual)

• ovaries

• male or ambiguous external genitalia

• due to excess androgens (e.g., congenital adrenal hyperplasia)

Male Pseudohermaphrodite (XY Individual)

• testes

• female external genitalia

• due to decreased androgen effects (most common →testicular feminization)

Androgen Insensitivity Syndrome (XY Individual)

• testicular feminization

• Müllerian duct regression (due to MIF)

• Wolffian duct regression (due to lack of testosterone receptors)

• phenotypic female (due to lack of receptors for DHT)

Decreased 5-a-Reductase (XY Individual)

• formation of testes (due to presence of Y chromosome)

• Müllerian duct regression (due to MIF)

• Wolffian duct development (due to testosterone)

• decreased DHT (due to lack of 5-α-reductase)

• variable external genitalia (due to decreased DHT)

Turner’s Syndrome (XO Individual)

• streak gonads (due to lack of two X chromosomes)

• Müllerian duct development (due to lack of MIF)

• Wolffian duct regression (due to lack of testosterone)

• external female (due to lack of DHT)

• decreased secondary female characteristics (due to decreased estrogen)

Congenital Adrenal Hyperplasia (XX Individual)

• development of ovaries (due to two X chromosomes)

• Müllerian duct development (due to lack of MIF)

• Wolffian duct regression (due to lack of local testosterone production)

• external male (due to excess systemic formation of DHT)

B Cells

• form plasma cells that secrete immunoglobulin

• surface antigen receptor composed of immunoglobulin

• rearrange immunoglobulin genes from germ line configuration

• CD19 → pan–B cell marker

• CD20 → pan–B cell marker, also called L26

• CD21 → pan–B cell marker, receptor for EBV

• CD22 → pan–B cell marker

T Cells

• secrete lymphokines

• surface antigen receptor (TCR) is attached to CD3

• rearrange genes for T cell receptor

• CD2 → receptor for sheep erythrocyte (E rosette)

• CD3 → attached to T cell receptor

• CD4 → helper T cells, bind with MHC class II antigens

• CD5 → pan–T cell marker

• CD7 → pan–T cell marker

• CD8 → cytotoxic T cells, bind with MHC class I antigens

Natural Killer Cells

• large granular lymphocytes

• do not need previous sensitization

• CD16 → receptor for Fc portion of IgG

IgM

• large molecule (pentamer)

• secreted early in immune response (primary response)

• cannot cross the placenta

• can activate complement

• contains a J chain

IgG

• most abundant immunoglobulin in serum

• secreted during second antigen exposure (secondary or amnestic response)

• can cross the placenta

• can activate complement

• can function as opsonin

IgE

• allergies, asthma, parasitic infection

• found attached to the surface of basophils and mast cells

• participates in type I hypersensitivity reactions

IgA

• usually a dimer with a J chain and a secretory component

• found along GI tract and respiratory tract

• secretory immunoglobulin

• can activate alternate complement pathway

CD4+ Cells

• helper T lymphocytes

• respond to MHC class II antigens

Subtypes:

1. T helper-1 (TH1) cells

• secrete → IL-2, IL-3, GM-CSF, γ-interferon, and lymphotoxin

(β-TNF)

• stimulate cell-mediated immune reactions → fight intracellular

organisms

2. T helper-2 (TH2) cells

• secrete → IL-3, IL-4, IL-5, IL-6, IL-10, and GM-CSF

• stimulate antibody production → fight extracellular organisms

CD8+ Cells

• cytotoxic T lymphocytes

• respond to MHC class I antigens

MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)

Class I Antigens

• found on all nucleated cells

• transmembrane α glycoprotein chain with β2-microglobulin

• react with antibodies and CD8-positive lymphocytes

• fight virus-infected cells and transplants

Class II Antigens

• found on antigen-presenting cells, B cells, and T cells

• transmembrane α chain and β chain

• react with CD4-positive lymphocytes

• fight exogenous antigens that have been processed by antigen-presenting

cells

DISEASES ASSOCIATED WITH HLA TYPES

• ankylosing spondylitis → HLA-B27

• primary hemochromatosis → HLA-A3

• 21-hydroxylase deficiency → HLA-BW47

• rheumatoid arthritis → HLA-DR4

• insulin-dependent (type I) diabetes mellitus → HLA-DR3/DR4

• systemic lupus erythematosus → HLA-DR2/DR3

HYPERSENSITIVITY REACTIONS

Type I

• binding of antigen to previously formed IgE bound to mast cells and

basophils

• release of histamine and leukotrienes C4 and D4

• urticaria (hives)

• anaphylaxis

Type II

• antibody (IgG or IgM) binds to antigens in situ

• cells destroyed by complement or cytotoxic cells (antibody-dependent cell-mediated cytotoxicity)

• linear immunofluorescence (IF)

• transfusion reactions

Type III

• antibody (IgG or IgM) binds to antigens forming immune complexes

• granular IF

• systemic → serum sickness

• local reaction → Arthus reaction

Type IV

1. Delayed type hypersensitivity

• CD4 lymphocytes

• extrinsic antigen associated with class II MHC

• formation of activated macrophages (epitheloid cells) →granulomas

• PPD skin test

• contact dermatitis (poison ivy, poison oak)

2. Cell-mediated immunity

• CD8 lymphocytes

• intrinsic antigen associated with class I MHC

• viral infections and transplant rejection

AUTOANTIBODIES

Nuclear

• diffuse (homogenous) → DNA (many diseases), histones (drug-induced SLE)

• rim (peripheral) → double-stranded DNA (SLE)

• speckled (non-DNA extractable nuclear proteins) → Smith (SLE), SS-A and SS-B (Sjögren’s syndrome), Scl-70 (progressive systemic sclerosis)

• nucleolar (RNA) → many (e.g., progressive systemic sclerosis)

• centromere → CREST syndrome Cytoplasmic

• mitochondria → primary biliary cirrhosis Cells

• smooth muscle →lupoid hepatitis (autoimmune chronic active hepatitis)

• neutrophils → Wegener’s granulomatosis and microscopic polyarteritis

• parietal cell and intrinsic factor → pernicious anemia

• microvasculature of muscle → dermatomyositis

Proteins

• immunoglobulin → rheumatoid arthritis

• thyroglobulin → Hashimoto’s thyroiditis

Structural Antigens

• lung and glomerular basement membranes → Goodpasture’s disease

• intercellular space of epidermis → pemphigus vulgaris

• epidermal basement membrane → bullous pemphigoid

Receptors

• acetylcholine receptor → myasthenia gravis

• thyroid hormone receptor → Graves’ disease

• insulin receptor → diabetes mellitus

ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCAs)

1. C-ANCAs (cytoplasmic)

• proteinase 3 → Wegener’s granulomatosis

2. P-ANCAs (perinuclear)

• myeloperoxidase → microscopic polyarteritis

AMYLOIDOSIS

Amyloid

• any protein having β-pleated sheet tertiary configuration

• apple-green birefringence with Congo red stain

 

Systemic Deposition

• multiple myeloma → deposits of amyloid light protein

• chronic inflammatory diseases → deposits of amyloid-associated protein

• hemodialysis → deposits of β2-microglobulin

 

Localized Deposition

• senile cardiac disease → deposits of amyloid transthyretin

• Alzheimer’s disease → deposits of β2-amyloid protein

• medullary carcinoma of thyroid → deposits of procalcitonin

• non-insulin-dependent diabetes mellitus (type II) →amyloid deposits in islets of Langerhans of pancreas

Chédiak-Higashi Syndrome

• autosomal recessive

FAMILIAL HYPERLIPIDEMIA

Type I Hyperlipoproteinemia

• familial hyperchylomicronemia

• mutation in lipoprotein lipase gene

• increased serum chylomicrons

Type II Hyperlipoproteinemia

• familial hypercholesterolemia

• mutation involving LDL receptor

• increased serum LDL

• increased serum cholesterol

Type III Hyperlipidemia

• floating or broad β disease

• mutation in apolipoprotein E

• increased chylomicron remnants and IDL

• increased serum triglycerides and cholesterol

Type IV Hyperlipidemia

• familial hypertriglyceridemia

• unknown mutation

• increased serum VLDL

• increased serum triglycerides and cholesterol

Type V Hyperlipidemia

• mutation in apolipoprotein CII

• increased serum chylomicrons and VLDL

• increased serum triglycerides and cholesterol

ANEURYSMS

Atherosclerotic Aneurysms

• cause → atherosclerosis

• location → abdominal aorta (between renal arteries and bifurcation of the aorta)

• pulsatile mass

• may rupture → sudden, severe abdominal pain in male older than 55

• treat with surgery when diameter is > 5 cm

 

Luetic Aneurysms

• cause → syphilis (treponema) infection

• obliterative endarteritis (plasma cells around small blood vessels)

• location → ascending (thoracic) aorta

• may produce aortic regurgitation or rupture

 

Dissecting Aneurysms

1. Due to cystic medial necrosis of aorta

• hypertension

• Marfan’s syndrome → due to defect in fibrillin gene

2. “Double-barrel” aorta on x-ray

 

Berry Aneurysms

• location → bifurcation of arteries in circle of Willis

• most commonly bifurcation of anterior communicating artery

• subarachnoid hemorrhage

• associated with polycystic renal disease

CARDIAC HYPERTROPHY

Concentric Hypertrophy

• response to pressure overload (e.g., hypertension or aortic stenosis)

• sarcomeres proliferate in parallel

• increased ventricular thickness

• no change in size of ventricular cavity

 

Eccentric Hypertrophy

• response to volume overload

• sarcomeres proliferate in series

• no increase in ventricle thickness

• increase in size of ventricular cavity

CONGENITAL HEART DEFECTS

Left-to-Right Shunts

1. Ventricular septal defect (VSD) → most common congenital cardiac

anomaly

2. Atrial septal defect (ASD)

3. Patent ductus arteriosus (PDA)

• “machine-like” heart murmur

• indomethacin closes PDA

 

Right-to-Left Shunts

1. Tetralogy of Fallot (TOF) → most common cause of congenital cyanotic

heart disease

• pulmonary stenosis

• ventricular septal defect

• dextropositioned (overriding) aorta

• right ventricular hypertrophy

 

No Shunts

1. Coarctation of the aorta

• infantile type (preductal)

• adult type (postductal) → rib notching, increased BP in upper

extremities, decreased BP in lower extremities

2. Transposition of the great vessels

• need shunt to be present in order to survive (e.g., PDA)

• PGE keeps ductus open

ATROPHY OF THE STOMACH

Type A ÆAutoimmune Gastritis

• autoantibodies to parietal cells and intrinsic factor → pernicious anemia

• decreased vitamin B12 → megaloblastic anemia

• increased serum gastrin levels

• histologic changes found in fundus of stomach

Type B Æ Environmental

• no autoantibodies present

• associated with Helicobacter pylori (urease breath test is positive)

• decreased serum gastrin levels

• histologic changes found in antrum of stomach

Ulcerative Colitis

• crypt abscesses (microabscesses) and crypt distortion

• disease begins in rectum and extends proximally (no skip lesions)

• does not involve small intestines

• superficial mucosal involvement (not transmural)

• increased risk of colon cancer and toxic megacolon

Crohn’s Disease

• granulomas

• segmental involvement (skip lesions)

• may involve small intestines (regional enteritis or ileitis)

• transmural involvement → fissures, fistulas, and obstruction

GALLSTONES

Cholesterol Stones

• yellow stones

• risk factors → Fs = fat, female, fertile, forty, fifty

• increased incidence in Native Americans

Bilirubin (Pigment) Stones

• black stones

• risk factors → chronic hemolysis and infections of biliary tract

• increased incidence in Asians

CONGENITAL ADRENAL HYPERPLASIA (CAH)

21-Hydroxylase Deficiency

• decreased cortisol → increased ACTH

• decreased aldosterone

• sodium loss in the urine → salt-wasting form of CAH

• hyperkalemic acidosis

• virilism in females

11-Hydroxylase Deficiency

• decreased cortisol → increased ACTH

• decreased aldosterone

• increased DOC and 11-deoxycortisol → increased mineralocorticoid

effects

• sodium retention → hypertensive form of CAH

• hypokalemic alkalosis

• virilism in females

17-Hydroxylase Deficiency

• decreased cortisol → increased ACTH

• no decreased aldosterone

• decreased sex hormones

• females → primary amenorrhea

• males → pseudohermaphrodites

MULTIPLE ENDOCRINE NEOPLASIA

Type 1 (Wermer’s Syndrome)

• parathyroid

• pituitary

• pancreas

Type 2 (Sipple’s Syndrome)

• parathyroid

• medullary carcinoma of thyroid

• pheochromocytoma

Type 3 (MEN 2B)

• medullary carcinoma of thyroid

• pheochromocytoma

• mucosal neuromas

Nephrotic Syndrome

• marked proteinuria → hypoalbuminemia and edema

• increased cholesterol → oval fat bodies in the urine

Examples (nonproliferative glomerular disease):

1. Minimal change disease (lipoid nephrosis)

• normal light microscopy

• EM reveals fusion of foot processes of podocytes

2. Focal segmental glomerulosclerosis (FSGS)

3. Membranous glomerulonephropathy (MGN)

• thickening of basement membrane (“spikes and domes”)

• uniform subepithelial deposits

4. Diabetes mellitus

Nephritic Syndrome

• hematuria (red blood cells and red blood cell casts in urine)

• variable proteinuria and oliguria

• retention of salt and water (hypertension and edema)

 

Examples (proliferative glomerular disease):

1. Focal segmental glomerulonephritis (FSGN)

• mesangial deposits of IgA

• Berger’s disease

2. Acute (diffuse) proliferative glomerulonephritis (DPGN)

• post-streptococcal glomerulonephritis

• large, irregular subepithelial deposits

3. Membranoproliferative glomerulonephritis (MPGN)

• subendothelial deposits → type I MPGN

• intramembranous deposits →type II MPGN (dense deposit disease)

• splitting of basement membrane by mesangium → “tram-track”

appearance

4. Rapidly progressive glomerulonephritis (RPGN)

GLOMERULAR DEPOSITS

Subepithelial

• diffuse proliferative glomerulonephritis (DPGN) → irregular and large

• membranous glomerulonephropathy (MGN) → uniform and small

Intramembranous (Basement Membrane)

• membranoproliferative glomerulonephritis (MPGN), type II

Subendothelial

• membranoproliferative glomerulonephritis, type I

• SLE

Mesangial

• focal segmental glomerulonephritis (FSGN)

• Henoch-Schönlein purpura

RAPIDLY PROGRESSIVE

GLOMERULONEPHRITIS (RPGN)

Linear Immunofluorescence

• antimembrane antibody

• Goodpasture’s disease

Granular Immunofluorescence

• immune complexes

• other glomerular or systemic disease

Minimal or Negative Immunofluorescence

• pauci-immune disease

• Wegener’s granulomatosis

• microscopic polyarteritis nodosa

CEREBRAL HEMORRHAGE

Epidural Hematoma

• severe trauma

• arterial bleeding (middle meningeal artery)

• symptoms occur rapidly

Subdural Hematoma

• minimal trauma in elderly

• venous bleeding (bridging veins)

• symptoms occur slowly

Subarachnoid Hemorrhage

• rupture of berry aneurysm

• “worst headache ever”

• bloody or xanthochromic spinal tap

INFECTIONS OF THE MENINGES

Bacterial Infections

• increased neutrophils and protein in CSF

• decreased glucose in CSF

• life-threatening

                Neonates - Escherichia coli

                6 months to 6 years - Streptococcus pneumoniae

                6 years to 16 years - Neisseria meningitidis (meningococcus)

                Older than 16 years - Streptococcus pneumoniae

                Epidemics -  Neisseria meningitidis

Viral Infections

• increased lymphocytes in CSF

• normal glucose in CSF

• mild and self-limited

Alzheimer’s Disease

• diffuse atrophy of cerebral cortex

• dementia (most common cause in elderly)

• senile plaques (with β-amyloid core)

• neurofibrillary tangles (with abnormal τ protein)

Pick’s Disease

• unilateral frontal or temporal lobe atrophy

Huntington’s Disease

• trinucleotide repeat disorder

Parkinson’s Disease

• substantia nigra (depigmentation)

• decreased dopamine in corpus striatum

• cogwheel rigidity and akinesia

• tremor

• treatment → dopamine agonists

Rheumatoid Arthritis

• rheumatoid factor (IgM antibody against antibody)

• pannus formation in synovium (hyperplastic synovium with lymphocytes

and plasma cells)

• ulnar deviation of fingers

• subcutaneous rheumatoid nodules (at pressure points)

• pain worse in morning (“morning stiffness”); pain decreases with

activity

Osteoarthritis

• degenerative joint disease (“wear and tear”)

• loss of articular cartilage → smooth subchondral bone (eburnation)

• osteophyte formation (DIP →Heberden’s nodes, PIP →Bouchard’s nodes)

• pain worse in evening; pain increases with activity

Gout

• hyperuricemia → precipitation of monosodium urate crystals (needleshaped,

negatively birefringent crystals)

• first MTP joint (big toe)

• tophus formation

• increased production of uric acid → Lesch-Nyhan syndrome

• increased turnover of nucleic acid → leukemias and lymphomas

• decreased excretion of uric acid →chronic renal disease, ethanol intake,

diabetes

ENZYMES

Aminotransferases (AST,ALT)

• myocardial infarction (AST)

• alcoholic hepatitis (AST > ALT)

• viral hepatitis (ALT > AST)

Creatine Kinase (CK or CPK)

• myocardial infarction (CPK-MB)

• muscle diseases (DMD)

Lactate Dehydrogenase (LDH)

• myocardial infarction (LDH1, LDH2)

Amylase or Lipase

• acute pancreatitis

HISTOLOGIC “BODIES”

1. Psammoma body:

• papillary carcinoma of the thyroid

• papillary tumors of the ovary

• meningioma

2. Immunoglobulin

• Russell body → cytoplasmic or extracellular

• Dutcher body → nucleus (Waldenstrom’s)

3. Councilman body → viral hepatitis

4. Mallory body → alcoholic hyaline

5. Cowdry A body → herpes

6. Aschoff body → rheumatoid fever

7. Ferruginous body → asbestos

8. Negri body → rabies

9. Lewy body → Parkinson’s

10. Heinz body (denatured hemoglobin) → G6PD deficiency

11. Barr body → number of X chromosomes minus one

HEALING OF THE MYOCARDIUM AFTER A MYOCARDIAL INFARCTION

0–12 h None Usually none (?wavy fibers)

12–24 h Pallor Coagulative necrosis

1–3 days Hyperemic (red) border Above+neutrophils

4–7 days Pale yellow Above + macrophages

7–14 days Red-purple border Above + granulation tissue

>2 weeks Gray-white scar Fibrosis (scar)

Caption:


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