Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
2003
-
INTEGRATED PATHOLOGY NOTES "
n e following are high yield facts that are meant to complement the notes. Some of the items cover
concepts that are taught by other teachers in the course that directly relate to pathology. Other items cover
topics that I do not have time to teach during the review (e.g., environmental pathology, nutrition, and
i-unopathology). Some items are clinical scenarios on high yield subjects that I use on exams and
quizzes for my own students that will provide you with additional questions to quality control what you
have learned.
Terms for lab test results: true positive (TP)- positive test result in a patient with the disease,
false negative (FN)-negative (normal) test result in a patient with the disease, true negative
-
(TN)-negative (normal) test result in a patient without the disease, false positive (FP)- positive
test result in a patient without the disease, negative predictive value of a test result ( P o -
chance that a negative (normal) test result is a TN rather than a FN, positive predictive value of a
test result (Pq - that a positive test result is a TP rather than a FP
chance
Sensitivity of a test:
1. "positivity in diseasew- formula for sensitivity: TP / TP + FN
2. use of a test with 100 % sensitivity- best used to screen for disease, excludes disease
when the test result returns negative, includes people with disease when the test result
returns positive, buzz words: excludes and includes
3. negative predictive value (PV-) of a test with 100% sensitivity- P V must be 100% since
there are no FN test results in a test with 100% sensitivity- this underscores why tests with
100% sensitivity exclude disease when the test result returns negative, e.g., serum
-
antinuclear antibody test (ANA) has 100% sensitivity in patients with SLE, therefore
repeatedly negative serum ANAs excludes SLE
SLE No SLE
Positive test (TP) 100 (Fp) 20
- Negative test (FN) 0 (TN) 80
Sensitivity of ANA: TP / TP + FN = 100 / 100 + 0 = 100%
PV-:TN/TN+FN=80/80+0=100%
4. positive predictive value (PV+)of a test with 100% sensitivity- test result is either a TP
or FP, therefore, the PV+ is never 100% owing to the chance that it may be a FP, p e o ~ l e
with the disease are alwavs included, e.g., a positive serum ANA result includes all people
with SLE, however, it does not confirm SLE since other diseases also have a positive serum
ANA (e.g., rheumatoid arthritis, progressive systemic sclerosis)
SLE No SLE
Positive test (TP) 100 (FP) 20
--
Negative test (FN) 0 (TN) 80
PV+=TP/TP+FP=IOO/ 100+20=83%
Specificity of a test:
.- 1. "negativity in healthw- formula for specificity is TN / TN + FP
2. use of a test with 100% specificity- confirms disease since there are no FP test results
3. PV in a test with 100% specificity- is always loo%, since the FP rate is zero- this
underscores why test with 100% specificity are used to confirm disease, e.g., anti-Sm for
SLE has 100% specificity (no FPs) and 30% sensitivity- all patients with a positive anti-Sm
have SLE
SLE No SLE
Positive anti-Sm (TP130 @no
Negative anti-Sm (FN)70 (TN)lOO
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
0
Accuracy: good
Precision: good Precision: good
Effect of decreasing the upper limit of normal of a test reference interval (e.g., lowering the
fasting glucose level for diagnosing diabetes mellitus [DM] from >I40 mg/dL to >I26 mg/dL)
on sensitivity, specificity, PV,and PV:
1. increases sensitivity and negative predictive value (PV) -
A. dropping the upper limit to a lower value means that more people with a negative test
result are likely to be TNs (not have DM) rather than FNs
B. sensitivity and P V always increase when the upper limit of a test is lowered
2. decreases specificity and positive predictive value (Po-
A. fewer people are likely to have DM, a test result >I26 mg/dL is more likely to be a FP
than a TP test result
B. summary schematic
I\ Normal Disease
-
Interval 0 - 4
Sensitivity 100% (no FNs)
Pv- 100%
Specificity decreases
PV+decreases
A
Interval 0 - 10
Specificity 100% (no FPs)
PV' 100%
Sensitivity decreases
PV- decreases
" Prevalence:
1. Prevalence (number of people with disease in the population studied) = Incidence
(number of new cases over a period of time) x Duration of the disease-
A. P=IxD
B. as duration (D) decreases, prevalence (P) decreases
C. as D increases, P increases
D. incidence is a constant in this relationship
E. PV+ increases when prevalence increases: more TPs
F. PV- increases when prevalence decreases: more TNs
2. prevalence calculation- TP + FN (all people with disease)/ TP + FN + TN + FP (all people
with and without disease)
3. example- if treatment for leukemia lengthens the survival period but does not lead to its
cure, prevalence (P) of leukemia increases owing to the increase in duration (D): no effect on
incidence (number of new cases of leukemia)
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Disease No Disease
2. potassium-
A. pseudohyperkalemia
B. K+ is the major intracellular cation
C. ECG will not show a peaked T wave
Lipid most affected by fasting:
1. triacylglycerol (TG) component coming from chylomicrons- chylomicrons contain diet-
derived TG
2. fasting or lack of fasting does not affect cholesterol (CH) and high-density Lipoprotein
(HDL) concentration-
A. normally, CH is < 3% of the chylomicron fraction
B. fasting is unnecessary for an accurate CH or HDL-CH
3. fasting is necessary for an accurate calculated low-density lipoprotein &DL)-
A. LDL = CH - HDL - TG/5 (VLDL fraction)
B. if TG is falsely increased by chylomicrons from the diet, it will falsely lower the
calculated LDL and falsely increase VLDL (TGI5)
Laboratory test alterations in alcoholics:
1. enhancement of the liver cytochrome P-450 system-
A. increased synthesis of y- glutamyltransferase (GGT)
B. excellent enzyme marker for alcoholic liver disease
2. increased production of NADH in its metabolic breakdown causes biochemical reactions
involving NADH to move in its direction resulting in the following-
A. lactic acidosis: pyruvate* lactate
B. fasting hypoglycemia: pyruvate is unavailable for gluconeogenesis
C. hypertriacylglycerolemia: 1,3 bisphosphoglycerate* dihydroxyacetone phosphate-,
glycerol 3-phosphate* TG
3. increase in ketoacid synthesis-
A. acetyl CoA: the end product of alcohol metabolism is used in the following reaction
B. acetyl CoA + acetyl CoA +
C. acetoacetyl CoA*
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Cri-du-chat: deletion of short arm of chromosome 5, mental retardation, cry like a cat
Microdeletion syndromes: loss of a small portion from 1 chromosome can only identified with
high resolution techniques, microdeletion on chromosome 15 may result in the Prader-Willi
syndrome- * chromosome 15 deletion is of paternal orierin, obesity, * hypogonadism, mental
retardation, microdeletion on chromosome 15 may result in Annelman syndrome- * chromosome
15 deletion is of maternal origin, * "happy puppy" syndrome (child always happyflaughing but
cannot talk), term applied to these syndromes is genomic imprinting
Genetics disorders in African-Americans: sickle cell traivdisease- 8-10% prevalence of sickle
cell gene, a-IP-thalassemia, glucose 6-phosphate dehydrogenase (G6PD) deficiency,
hereditary persistence of HgbF
Genetic disorders in Ashkenazi Jews: factor XII deficiency, Gaucher's disease, Tay-Sachs
disease
Genetic disorder in Northern Europeans: cystic fibrosis- MC genetic disease interfering with the
patient's abilitv to reproduce owing to early death or problems with fertility
Genetic disorders in Mediterranean peoples: G6PD deficiency, sickle cell traivdisease, P-
thalassemia
Genetic disorder in Southeast Asians: a-thalassemia
MC genetic syndrome associated with advanced maternal age: trisomy 21
Down syndrome pathogenesis: trisomy 21- * 95% of all cases, * 47 chromosomes, * maternal
origin for extra chromosome, Robertsonian translocation- * 4%, * 46 chromosomes in child, *
mother with 45 chromosomes- usually mother, MC genetic cause of mental retardation- IQ
25-50 in 80%
Down's clinical findings: epicanthal folds with upward slanting, simian palmar crease, poor
reflexes/hypotonicity, cardiovascular- * endocardia1 cushion defects (combined ASD and VSD),
major determining factor for survival in early infancy and childhood, GI- * duodenal atresia
(polyhydramnios, vomit. bile at birth, double bubble sign on x-ray), * Hirschsprun~'~ disease ,
hematologic- increased incidence of leukemia, CNS- * Alzheimer's disease, * chromosome 21
codes for P-amyloid proteins, which are converted into amyloid and' are toxic to neurons, *
universal by age 35 (any patient with Alzheimer's disease under 40 is a patient with Down
syndrome), reproductive- * all males are sterile, * females have 50% chance of having a child
with Down's
Risk for future children with Down's: 1-2% overall risk for trisomy 21, maternal age-
women >35 yrs of age, * 5-15% risk for parent with a balanced translocation, * karyotype of
affected child should always be determined to evaluate risk for siblings to have affected children
Mendelian disorders in descending order of frequency: autosomal dominant (AD),
autosomal recessive (AR), sex-linked recessive (SXR), sex-linked dominant (SXD)
AD disorders: only 1 abnormal allele is necessary to express the disease- * "dominant gene", *
e.g., aa (disease, usually lethal) or Aa (disease), only one parent has to have the gene to uass it on
to their children, one affected parent + normal parent- 50% normal children, 50% affected
children
AR disorders: both abnormal alleles must be present (homozygous) to express the disease- * aa
(disease), * Aa (heterozygote asymptomatic canier), both parents must have the abnormal allele-
* 2 asymptomatic carriers (children- 25% normal AA, 50% Aa, 25% aa), * patient with the disease
has children with an asymptomatic carrier (children 50% Aa, 50% aa)
SXR disorders: males with abnormal allele express disease- males are "homozygous", since they
only have 1 X chromosome, affected males transmit the disease to both daughters - but none of
their sons- daughters are usually asymptomatic carriers, female carrier transmits the disease to
50% of the boys and 25% of daughters are asymptomatic carriers, female carrier + affected male-
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
50% of males are affected, 25% of females are asymptomatic carriers, 25% of females are
symptomatic- maternal and paternal X chromosome are abnormal
SXD disorders: males and heterozygous females both express the disease
w AD disorders: associated with stmctural defects in proteins and receptors- * enzyme deficiencies
are uncommon, * AD disorders that are enzyme deficiencies- acute intermittent porphyria
(deficiency of uroporphyrinogen synthase), * hereditary angioedema (C1 esterase inhibitor
deficiency), late manifestations of disease- e.g., Huntington's disease with choreddementia later
in life, exhibit penetrance- * person has the abnormal gene but never expresses the disease,
however, the gene is transmitted to their children, * some AD disorders have 100% penetrance
(e.g., familial polyposis, adult polycystic kidney disease), while others have incomplete penetrance
(e.g., Marfan's), exhibit variable expressivihr- affected people have different levels of severity of
the disease, mechanisms of AD disease without a family Hx:* MCC is incomplete Denetrance, *
new mutation, examples of AD diseases (in order of decreasing frequency): * von Willebrand's
disease * familial hypercholesterolemia, adult polycystic kidney disease, hypertrophic
cardiomyopathy, * Huntington's disease, * neurofibromatosis, * congenital spherocytosis, *
familial polyposis, * acute intennittent porphyria, * osteogenesis imperfecta, * Marfan syndrome
Q= Example of a pedigree with complete penetrance:
D--r.
I
Q= AR diseases: no evidence of- penetrance, variable expressivity, late manifestations, most (not
all) AR diseases are -- inborn errors of metabolism- * acute intermittent
porphyria and C1 esterase inhibitor deficiency are both autosomal dominant, * G6PD and Lesch-
Nyhan are both SXR, examples of those that are not enzvme deficiencies- * cystic fibrosis, *
sickle cell traitldisease, * hemochromatosis, * Wilson's disease
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Example of an AR pedigree:
w-
*
0 *
SXR disorders: examples (in order of decreasing frequency): * fragile X syndrome, * G6PD
deficiency, * Duchenne's muscular dystrophy, * hemophilia AIB, * severe combined
immunodeficiency, * Wiskott-Aldrich syndrome, * testicular feminization, * color blindness, *
chronic granulomatous disease of childhood, *Bruton's agammaglobulinemia
IIV
Fragile X syndrome: l some geneticists say it is a sex-linked dominant disease, owing to the fact
that female carriers may express the disease in future generations (concept of anticipation), l
second MC genetic cause of mental retardation, l MC Mendelian disorder associated with mental
retardation, l clinical- * mental retardation, * macroorchidism- at puberty, * -30% of female
carriers are mentally retarded or have impaired learning- due to anticipation and addition of
trinucleotide reveats with future venerations, l abnormal fragile X chromosome- DNA analysis for
carrier identification (identify CGG trinucleotide repeat is the best test to confirm)
* Lesch Nyhan syndrome: OSXRdisease with a deficiency of HGPRT- no inhibition of PRPP in
purine metabolism, l clinical- * hypenuicemia, * mental retardation, * self mutilation
* SXD disorders: percentages - of children with the abnormal allele are the same as those in SXR
disorders: * dominant abnormal allele causes disease in both males and females, * affected woman
transmits symptomatic disease to 50% of her daughters and 50% of her sons, * affected males
transmit symptomatic disease to all of their daughters and none of their sons, l examples: * familial
hypophosphatemia (defect in the proximal reabsorption of phosphate and conversion of 25(OH)D3
to 1,25 (OH)2-D3), * glomemlonephritis associated with nerve
deafness)
examples: * cleft lip or palate, * congenital heart disease, * coronary artery disease, * gout, * type
11 DM, * essential hypertension, * open neural defects, * congenital pyloric stenosis
G- Mitochondria1 DNA disorders: mtDNA primarily codes for enzymes involved in mitochondria1
oxidative phosphorylation reactions, ova contain mitochondria- affected women transmit
symptomatic abnormal allele to all their children, sperm lose their mitochondria during
fertilization- affected males do not transmit abnormal allele to any of their children,
examples: * Leber's hereditarv optic neuropathv. * myoclonic epilepsy, * lactic acid with stroke
Example of a mtDNA pedigree:
Calculation of the prevalence of a genetic disease given the carrier rate: e.g., cystic fibrosis
(CF), with a carrier rate of CF is 1125- * number of couples at risk is equal to the carrier rate in
males x the carrier rate in females, or 1/25 x 1/25 = 11625 couples are at risk, * risk of having a
child with CF (AR disease) is 114, hence 11625 x 114 = prevalence of -112500
Simple way of calculating the carrier rate of a disease given the prevalence of a genetic
disease (Hardy Weinberg equation): reflects the distribution of a mutant gene in the population,
example using prevalence of CF of 112500- * number of couples at risk = 112500 i 114 = 11625, *
carrier rate of CF = 114625 = 1/25
Deformations: anatomical defects resulting from mechanical factors (extrinsic forces) that
usually occur in the last two trimesters after organs have developed, e.g., oligohydrarnnios
producing facial and limb abnormalities (called Potter's facies)
Malformation: disturbance (e.g., drugs, infection) that occurs in the morphogenesis of an
organ(s), hypospadias faulty closure of urethral folds, epispadias due to a defect in genital
tubercle, club foot, ventricular septa1 defect
Agenesis: anlage (primordial tissue) is absent (e.g., renal agenesis)
Aplasia: anlage is present but never develops
Hypoplasia: anlage develops incompletely, however, the tissue that is present is histologically
normal
Mechanisms of teratogens: teratogens are most detrimental during the embryonic period- * first
9 weeks of life (4th-5th week most sensitive for teratogens), * e.g., open neural defects occur when
tube normally closes between the 23rd-28th day, specific effects of some teratogens: * some
interfere with formation of mitotic spindle, * interfere with production of ATP, * some interfere
with gene production (e.g., isotretinoin effect on Hodhedgehog genes, which are important in
embryonic patterning)
Teratogen cocaine: maternal effects: * hypertension, * abruptio placenta, newborn effects: *
hyperactivity, * microcephaly (MC effect), * interruption of blood flow leading to infarction (CNS,
bowel, missing digits)
Maternal diabetes mellitus and the teratogenic effects in newborns: increased birthweight
(macrosomia, large for gestational age): * hyperinsulinism in the fetus from poor maternal glycemic
control increases muscle mass (insulin increases amino acid uptake in muscle), * hyperinsulinism
increases fat deposition (insulin increases deposition of TG in adipose), open neural tube defects,
cleft liplpalate, respiratory distress syndrome: fetal hyperinsulinism in response to maternal
hyperglycemia inhibits fetal surfactant production by type 11 pneumocytes
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
greater chance of fetal infection with primary rather than recurrent Herpes, clinical: local or
systemic disease (encephalitis, skin infections), Rx: acyclovir
* Congenital syphilis: primarily transplacental: uncommon infection during first 5 months of
pregnancy; anatomical barriers prevent access to the fetal circulation, early neonatal syphilis
(first 2 yrs): hepatomegaly MC sign, osteochondritis (inflammation of bone), mucocutaneous -
lesions, pneumonia alba (lobar pneumonia), persistent rhinitis (snuffles), late neonatal syphilis
(>2 yrs): frontal bossing is MC sign, saber shins, rhagades (perioral linear scars); Hutchinson's
triad: teeth (notched upper central incisors called Hutchinson's teeth and malformed molars called A -
mulberry molars), interstitial keratitis (blindness), sensorineural hearing loss, Rx: penicillin
Congenital Varicella-zoster virus: chorioretinitis- potential for blindness, limb hypoplasia,
cortical atrophy in the brain, vesicular skin lesions -
* Age dependent disorders (inevitable with age): increased body fat: decreases the number of
insulin receptors leading to glucose intolerance, respiratory: obstructive type of pattern in
pulmonary b c t i o n tests (so-called "senile emphysema"); decreased elasticity (reduced recoil on
--
expiration); decreased forced expiratory volume in 1 second (FEV,,,); decreased forced vital
capacity (FVC); increased total lung capacity (TLC); increased residual volume (RV); low normal
PaOz, cardiovascular: loss of elasticity in aorta, decreased cardiac output and heart rate in
response to stress; at rest, the cardiac output is unchanged, musculoskeletal: osteoarthritis in -
weight bearing joints, CNS: cerebral atrophy with mild forgetfulness, sensory changes:
cataracts; presbyopia (inability to focus on near objects); presbycusis (sensorineural hearing loss
particularly at high frequency); otosclerosis (fusion of the ear ossicles producing conductive -
hearing loss), immune system; decreased T cell b c t i o n (often anergic to common skin antigens,
positive PPD non-reactive or absent); loss of isohemagglutinins to blood antigens (may not
develop a hemolytic transfusion reaction if blood is mismatched), skin changes: loss of skin --
elasticity (increased cross-bridging of collagen); senile purpura over the dorsum of the hands
and lower legs where bumping into objects is most likely to occur; decreased sweating (eccrine
glands fibrosed, danger of heat stroke), GI tract: decreased gastric acidity; decreased colonic
motility (constipation which predisposes to diverticulosis); decreased activity of the hepatic
cytochrome P450 system(danger of drug toxicities), male reproductive: prostate
hyperplasia (increased urine residual volume with subsequent increase in urinary tract infections);
prostate cancer (only cancer that is age dependent); decreased testosterone, female
reproductive: breast and vulvar atrophy due to decreased estrogen; increased gonadotropins,
endocrine system: increased glucose intolerance (due to increase in body fat and subsequent
reduction in insulin receptor synthesis), renal changes: decreased GFR with reduction in the
creatinine clearance (risk of drug toxicity due to slow clearance of drugs)
Age-related changes (increased incidence in elderly but not inevitable): cardiovascular:
atherosclerosis with increased incidence of coronary artery disease, peripheral vascular disease, and
strokes; temporal arteritis; aortic stenosis (MC valvular abnormality in the elderly); systolic
hypertension due to loss of aortic elasticity, musculoskeletal system: osteoporosis (particularly
the vertebral column in females and femoral head in males); Paget's disease of bone, respiratory
system: pneumonia usually Streptococcus pneumoniae (underscores importance of Pneumovax
vaccination in elderly), CNS: Alzheimer's disease; Parkinson's disease; strokes (atherosclerotic
type is M C type of stroke); subdural hematomas (falls cause tearing of bridging veins in subdural
space leading to a venous clot), sensory changes: macular degeneration (MCC of blindness in
elderly), skin disorders: UVB light-induced cancers; actinic (solar) keratosis (precursor of
squamous cancer), endocrine system: type I1 diabetes mellitus
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Top 5 causes of death in males and females regardless of age and sex in the United States in
descending order: a heart disease, cancer, stroke, chronic obstructive pulmonary disease
(COPD), a motor vehicle accidents- MC COD in males and females between 1-39 yrs or age
Top 3 causes of death in children aged 1-14 yrs in descending order: accidents- * -50%
MVAs, * falls 25-30%, * burns 10-IS%), cancer, congenital anomalies
Top 3 risk factors leading to increased morbidity/mortality in the United States in descending
order: a cigarette smoking, dietary factors and activity patterns: high saturated fat, low fiber
diet; lack of exercise, alcohol abuse
Gunshot wounds: a contact wounds: contain soot and gunpowder in the wound (called fouling), a
intermediate wounds: powder tattooing (stippling of skin around the entrance site), a distant
wounds: no powder tattooing, exit wounds are larger and more irregular than entrance wounds
Motor vehicle accidents (MVAs): MCC accidental death between 1-39 yrs of age: commonly
alcohol-related, particularly in teenagers, seat belts and air bags have reduced
morbiditylmortality
Drowning: a common COD in children fi-om 1-14 yrs of age, near drowning: survival following
asphyxia secondary to submersion, wet drowning: 90% of cases; initial laryngospasm on contact
with water-, relaxation/aspiration of water, fieshlsalt water drowning: whether fresh or salt
water drowning, surfactant is destroyed in lungs-, atelectasis with intrapulmonary shunting-,
diffuse alveolar damage and initiates spasm in the bronchioles, immediate COD in drowning is
cardiac arrhythmia
Burns: first degree burns: painful partial thickness burns (e.g., sunburn); produce cell necrosis
limited to the epidermis; heal without scar, second degree burns: painful partial thickness burns;
involve entire epidermis; form blisters within epidermis, heal without scarring unless they are
deep, a third degree bums: painless full thickness bums; extensive necrosis of epidermistadnexa;
extensive scarring complicated by keloid formation (propensity for squamous cell carcinoma);
healing comes from residual epithelium at the marpins of the burn and from adnexal structures, a
C0D:infection due to most commonly to Pseudomonas aeruginosa followed by
Staphylococcus aureus, house fires: smoke inhalation MC COD; carbon monoxide (CO) and
cyanide poisoning commonly occur (source of cyanide is polyurethane in upholstery)
Heat injuries: hypertherrnia: core body temperature >37.2OC, heat cramps: afebrile; common
in untrained athletedlaborers who become volume depleted; lose excess amounts of saldwater, a
heat exhaustion: mild elevation in core body temperature (13g°C); common in athletes training
in hothumid environment; develop severe volume depletion, exertional type of heat
stroke: core body temperatures 2 41°C; people working or running on hot day; skin hoddry;
profound lactic acidosis; rhabdomyolysis common, non-exertional type of heat stroke:
elderly/chronically ill patients; skin hoddry without sweating (hypohidrosis); lactic acidosis1
rhabdomyolysis uncommon, malignant hyperthermia: AD disease; defect in calcium release
channels in the muscle sarcoplasmic reticulum; massive muscle contractions with extremely high
temperatures after induction of anesthesia by halothane and succinylcholine (muscle relaxant); Rx
with dantrolene; screen family members with muscle biopsy and caffeinehalothane contraction
test on muscle
Ionizing radiation: examples: y-rays; x-rays; particulate radiation emitted by radioactive
substances (alp particles), cell cycle: peak sensitivity is in G2 (synthesis of tubulin for mitotic
spindle) and M phase (assembly and disassembly of mitotic spindle); S phase least sensitive; GI
phase intermediate sensitivity, tissues with a high radiosensitivity: hernatopoietic cells are most
affected (e.g., lymphocytes > granulocytes > platelets > mature RBCs); germinal cells in the testes,
ovaries, a tissues with low radiosensitivity: brain is most resistant to radiation; bone; mature
cartilage; muscle, a total body irradiation: hematopoietic system first system affected (greatest
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Differential diagnosis of cavitary lesions in upper lobe: MCC is reactivation TI3 (not primary),
histoplasmosis, Klebsiellapneumoniae, squamous carcinoma
Patient with Marfan's syndrome has chest pain radiating into the back and a diastolic
murmur: aortic regurgitation due to stretching of aortic valve ring by the dissection
First step in work-up of a peripheral blood smear of microcytic anemia: order serum femtin,
a decreased in iron deficiency, increased in ACD, normal in mild a and P-thalassemia
Patient with twitching of face after tapping of facial nerve: tetany due to decrease in ionized
calcium- threshold potential is lowered so muscleJnerve are partially depolarized, Chvostek's
sign, a Trousseau's sign is when thumb adducts into palm when taking blood pressure
Patient taking penicillin for streptococcal infection develops hemolytic anemia with jaundice
and a positive direct Coomb's: due to autoimmune hemolytic anemia (type TT) against BPO
attached to RBC membrane
Main site for acetaminophen toxicity, shock, CO poisoning, alcohol in liver: around central
vein- least amount of oxygen in this site (zone III)
Differentiating mumps from pancreatitis: mumps only has increase in serum amylase, a
pancreatitis has increase in amylase and lipase
Differential diagnosis of a flank mass in a child: Wilm's tumor-associated with aniridia and
hemihypertrophy in the AD type of Wilms, renal dysplasia- MC cystic disease in children
Patient with viral myocarditis develops hypotension, neck vein distention, a drop in blood
pressure on inspiration, and muffled heart sounds: pericardial effusion fiom coxsackie
myocarditis- Bx of heart would show a lymphocytic infiltrate with destruction of muscle
Newborn baby girl, swelling of dorsum of handsJfeet (lymphedema), cystic mass in neck: a
lymphedema in child with Turner's syndrome, XO, defects in lymphatics, cystic mass in neck
due to dilated lymphatics that stretch skin and produce webbed neck
Smoker with painless jaundice with clay colored stools and varicosities in right upper
shoulder area: migratory thrombophlebitis in a patient with carcinoma of the head of pancreas
with obstruction of bile flow, called Trousseau's sign
Patient with diarrhea and episodic flushing of the skin, nodular liver (metastasis from
carcinoid tumor of terminal ileum), elevated urinary 5-hydroxyindoleacetic acid level, thick,
plaque-like deposits found on the tricuspid and pulmonic valve leaflets: carcinoid heart disease
16-yr-old died suddenly while playing basketball: hypertrophic cardiomyopathy, a asymmetric
hypertrophy of the interventricular septum with conduction defects, murmur intensity increases
(worse) with factors decreasing preload (standing, Valsalva, venodilator), murmur intensity
decreases (better) with factors increasing preload (sustained hand grip, squatting, lying down, P-
blockers)
Hypertensive infant has masses in the skin and lytic lesions in bone; small, basophilic staining
cells SlOO antigen positive, primary lesion in :adrenal medulla- neuroblastoma
Young girl with necrotic, bloody, grape-like mass protruding from the vagina; biopsy reveals
malignant cells with cross-striations; tumor stains negative for cytokeratin, factor VlII
related antigen, and carcinoembryonic antigen, and positive for desmin; cancer is most likely
derived from: muscle: embryonal rhabdomyosarcorna, MC sarcoma in children
Elderly woman with abdominal distention, primary cancer most likely responsible for
induration in pouch of Douglas on rectal examination: ovarian cancer- induration due to
seeding by the cancer
Elderly man with point tenderness in the lower vertebral column, elevated serum alkaline
phosphatase. What tests or procedures would be your first step in the evaluation of this
patient: digital rectal exam: think cheap, bone tenderness implies stage IV disease and DRE
should be positive, increased alkaline phosphatase suggests osteoblastic bone metastasis
Note: This material is copyrighted. All rights resewed. Edward Goljan, M.D. 2003
Metastatic adenocarcinoma in left supraclavicular node would most likely have its primary
origin in: stomach adenocarcinoma with mets to Virchow's node
15-yr old girl develops a sudden onset of right lower abdominal pain. Pregnancy test negative.
Cystic mass with densities in the right ovary noted on x-ray: cystic teratoma
An ulcerated lesion that develops in a keloid secondary to a third degree burn or an ulcer
located at the orifice of a chronically draining sinus that does not respond to medical
management is most likely due to: development of a squamous cell carcinoma
Hematuria in a 58-yr old smoker would most likely be associated with which of the following
groups of cancers: renal adenocarcinoma~transitionalcell carcinoma of the bladder both of which
are most commonly caused by smoking
Pneumoconiosis whose most common lesion is a benign pleural plaque: asbestosis
A woman with chronic headaches develops episodic asthmatic attacks. The most likely cause
is: ingestion of non-steroidal anti-inflammatory agents with release of leukotrienes: classic triad
asthma, nasal polyps may also be present
Medical student with intermittent bouts of diarrhea and constipation associated with
cramping right and left lower quadrant pain: imtable bowel syndrome: intrinsic motility
defect in bowel, flexible sigmoidoscopy is negative
Immunizations given at birth to a baby whose mother is positive for HBsAg: Hep B vaccine:
active immunization, HBIGa: passive immunization
A child has eaten raw hamburgers and now has a hemolytic anemia and renal failure: HUS
due to 0157: H7 serotype of E. coli, low platelet count and prolonged bleeding time
A 28-yr-old woman has an anterior mediastinal mass and non-tender lymphadenopathy in
the right supraclavicular node: nodular sclerosing Hodgkin's disease
A 75-year-old woman in a nursing home has non-palpable ecchymoses limited to the back of
her hands. A CBC is unremarkable. The patient most likely has: senile purpura
Which of the following vitamin toxicities predisposes a patient who is taking warfarin to bleed
and have an INR outside the normal range: vitamin E toxicity decreases the synthesis of vitamin
K dependent factors in the liver
A 30-year-old man with AIDS has pitting edema, hypertension, proteinuria > 3.5 g/24 hrs,
and fatty casts in the urine. A renal biopsy exhibits glomerular disease: focal segmental
glomerulosclerosis
A 29-year-old woman develops generalized pitting edema and hypertension. A renal biopsy
reveals diffuse glomerular disease with increased thickness of basement membranes and
hypercellularity. Silver stains reveal "tram track" splitting of the basement membranes. An
electron micrograph exhibits "dense deposits" in the glomerular basement membranes. The
patient has a persistently low serum C3: type 11MPGN or "dense deposit disease", patients
have C3 nephritic factor: autoantibody against C3 convertase in alternative system that causes it to
continually activate C3 causing very low levels
A 25-year-old man, who initially presented to the hospital with hemoptysis, has progressed
into renal failure. A renal biopsy shows linear immunofluorescence.: Goodpasture's syndrome:
patient has rapidly progressive crescentic glomerulonephritis
A 74-year-old man with colon cancer develops generalized anasarca. He has proteinuria > 3.5
g/24 hr and fatty casts in his urine. A renal biopsy shows diffuse glomerular disease. Silver
stains demonstrate epimembranous spikes and the presence of subepithelial deposits on
electron microscopy: diffuse membranous GN
A 10-yr-old boy living in Salt Lake City, Utah has bilateral sensorineural hearing loss, ocular
abnormalities, and glomerulonephritis. Both IF and EM are negative. Foam cells are noted in
visceral epithelial cells: Alport's syndrome: sex-linked dominant disease
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
A 65-yr-old man with chronic HCV hepatitis has a history of cyanosis of his hands, tip of
nose, and ears during cold weather. These findings subside when he comes indoors. He now
has palpable purpura in cold-exposed areas: cryoglobulinemia
A 12-year-old has a history of cellulitis -2 weeks ago. He now presents with periorbital
edema, hypertension, and smoky-colored urine. Urinalysis shows RBC casts with mild
proteinuria (1.5 g/24 h). Renal biopsy reveals a diffuse increase in cellularity along with a
neutrophilic infitrate. IF shows granular deposits. Subepithelial deposits are noted on EM:
acute post-streptococcal GN: immunologic reaction secondary to either a group A streptococcus
pharyngitis or skin infection
A 62-year-old woman with a long-history of severe rheumatoid arthritis and restrictive
cardiomyopathy now presents with pitting edema and hypercholesterolemia. Urinalysis
shows oval fat bodies and fatty casts. Protein dipstick is 2+, sulfosalicylic acid 2+. Renal
biopsy shows hyalinization of the glomerular mesangium. A special stain is ordered: systemic
arnyloidosis
An 89-year-old woman with a history of chronic HCV hepatitis from a blood transfusion now
presents with generalized puffiness and mild hypertension. Urinalysis shows oval fat bodies,
fatty casts with Maltese crosses, and 4+ protein (> 3.5 g protein124 hr). A renal biopsy reveals
hypercellular glomeruli with an increase in basement membrane thickness and tram-track
splitting of the basement membranes. The. IF is granular and EM reveals subendothelial
deposits. The patient has depressed levels of C3: type I MPGN with HCV association
A 24-year-old man with a prior history of an upper respiratory infection is noted to have
microscopic hematuria and mild proteinuria (1.5 g/24 hrs) during a routine physical exam.
He is not hypertensive. A renal biopsy shows a granular IF with predominantly IgA
deposition in the mesangium and electron dense deposits in the same area: IgA
glomerulonephritis
A 48-year-old woman has proteinaria (> 3.5 gm124 hrs), hypertension, and fatty casts in the
urine. A renal biopsy reveals eosinophilic nodular masses in the mesangium of the glomeruli,
hyaline arteriolosclerosis of the afferent and efferent arterioles, and increased thickness of the
basement membranes of the tubules. IF is negative. EM reveals fusion of the podocytes and
increased collagen deposition in the mesangium and basement membranes: nodular
glomerulosclerosis in diabetes mellitus
A 28-yr-old man, with a history of renal disease in his maternal grandfather, has end-stage
renal disease requiring dialysis. Physical exam reveals papular red lesions on his skin,
peripheral neuropathy, and corneal disease. Previous renal biopsies exhibited vacuolated
visceral epithelial cells which correspond with lamellar bodies on EM: Fabry's disease: SXR
disease with deficiency of a-galactocerebrosidaseA and accumulation of ceramide trihexoside
A normotensive 10-yr-old boy, with a previous history of an upper respiratory infection,
presents with generalized pitting edema. He has had problems with allergies since early
childhood. Urinalysis reveals proteinuria (> 3.5 g124 hrs), fatty casts, and oval fat bodies. His
clinical findings improve rapidly with high dose corticosteroids: lipoid nephrosis
A 25-yr-old woman presents with hypertension. A urinalysis reveals mild proteinuria,
hematuria, and RBC casts. A serum ANA exhibits a rim pattern. An anti-dsDNA titer is
extremely high: type IV SLE glomerulonephritis
Patient with Wegener's granulomatosis develops hematuria and an abnormal urine cytology:
transitional cell carcinoma, patient is on cyclophosphamide, which produces hemorrhagic
cystitis and TCC
An Egyptian man has microscopic hematuria and an abnormal urine cytology: squamous cell
carcinoma: patient has Schistosoma hemaiobium involving the bladder plexus
An uncircumcised male has an ulcerative lesion on the undersurface of the glans penis and
palpable inguinal adenopathy: squamous cell carcinoma (penis), lack of circumcision is
greatest risk factor
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
A man, who has worked with aniline dyes in the past, develops microscopic hematuria and an
abnormal urine cytology: transitional cell carcinoma. most likely it is bladder, but it could be
renal pelvis as well
A 72-yr-old man has bilateral painless masses in his testicles: malignant lymphoma:
metastatic, not primary, note the bilaterality
A patient with acute myelogenous leukemia developed acute renal failure after being treated
with multiple chemotherapy agents: increased release of purines led to increased production of
uric acid, whose crystals blocked the renal tubules resulting in ARF
Complication associated with sickle cell trait, acute pyelonephritis, analgesic abuse, and
diabetes mellitus: renal papillary necrosis
Patient who works outdoors all the time rubs a gray-white lesion off from the back of his
hand but it grew back after a few weeks: actinic (solar) keratosis- precursor for squamous cell
carcinoma
Inborn error of metabolism associated with pellagra: Hartnup's disease: loss of neutral amino
acids in the GI and GU tract; loss of tryptophan leads to pellagra due to decrease in synthesis of
niacin
African American took primaquine and then developed an anemia with bite cells: G6PD
deficiency
Patient with intense occipital headache and blood in CSP: subarachnoid bleed in a patient with a
ruptured congenital berry aneurysm
Sexually active man with sterile pyuria and no organisms seen on gram stain: Chlamydia
trachomatis non-specific urethritis
Patient that just returned from a trip to Australia develops severe dyspnea and chest pain:
developed DVT in the lower legs from sitting too long and now has a pulmonary embolus with
infarction
Man with severe hyponatremia and high urine osmolality: inappropriate ADH syndrome from
small cell cancer in the lung, high urine osmolality is due to increased peritubular hydrostatic
pressure and loss of sodium in the urine as well as constant concentration of the urine from excess
ADH
Intravenous drug abuser with fever and pansystolic murmur increasing on inspiration:
tricuspid regurgitation due to S. aureus infective endocarditis
Down syndrome patient with vomiting and maternal polyhydramnios: duodenal atresia
Down syndrome patient with constipation at birth: Hirschsprung's disease
Complications of prostate hyperplasia: infection, urinary retention, bladder diverticula
Patient with a mass in fallopian tube and an increase in PhCG: ectopic
A patient in the hospital accidentally gets infused with saline contaminated with E. coli and
develops shock. Two days later there is bleeding from all puncture sites. Diagnosis? DIC,
best test is D-dimers
MC vitamin deficiency in alcoholics: folate
Woman is a pure vegan and is breast feeding her baby and the baby develops anemia: BIZ
deficiency
When to give folate to prevent open neural tube defects: before pregnancy, neural tube is
already developed before the patient h o w s she is pregnant
Interpretation of a Schilling's test corrected with IF: PA
Drug causing a macrocytic anemia in a patient with severe rheumatoid arthritis: methotrexate,
which blocks dihydrofolate reductase
Drug young woman with hypertension and a macrocytic anemia is taking: birth control pills,
estrogen increases angiotensinogen, estrogen blocks reabsorption of monoglutamate
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Anemia in an infant that develops when switched from COW'S milk to goat's milk: * goat's milk
is low in folate, B6 (pyridoxine), iron and high in potassium, chloride, arachidonic acids, and
linoleic acids when compared to cow's milk
Prevention of macrocytic anemia in patients on methotrexate: leucovorin rescue (citrovorum
factor), replenishes ~ ~ " ~ - m e t h ~THF:
l e n esubstrate necessary for thymidylate synthesis
An AIDS patient develops diarrhea with an acid-fast organism. What is the most likely
cause?: Cryptosporidium
A patient with liver cirrhosis and ascites develops spontaneous bacterial peritonitis, what is
the most likely organism?: E. coli
Newborn has a puffy face, poor muscle tone, and diminished deep tendon reflexes: cretin
@ypothyroidism)
Previously healthy girl develops aplastic anemia. Cause?: parvovirus ,
Mother with polyhydramnios and fetus with anal atresia: VATER syndrome- vertebral defects,
-anal atresia, gacheo~sophagealfistula, xadial (absent) and renal abnormalities
Newborn with tetany and small ears: DiGeorge syndrome, 3rd and 4th pharyngeal pouches do
not develop (absent thymus and thymic shadow and absent parathyroids), expect hypocalcemia
Women with excessive weight loss (e.g., marathon runner, aerobics instructor, anorexia
nervosa): decrease secretion of GnRH from hypothalamus leading to decrease in gonadotropins-,
secondary amenorrhea-, osteoporosis (lack of estrogen)
Post-radical mastectomy-winged scapula: indicates injury to the long thoracic nerve; paralysis
of the serratus anterior muscle
Paralysis of upward gaze in an infant: hydrocephalus secondary to stenosis of the aqueduct of
Sylvius, this is called Parinaud's syndrome
Respiratory bronchiole: last airway structure with cilia, respiratory unit where gas exchange
occurs is the respiratory bronchiole, alveolar duct, and alveoli
Terminal bronchioles: cilia but no goblet cells, site of obstruction in asthma, cystic fibrosis,
and chronic bronchitis, site where turbulent air flow becomes laminar due to parallel branching of
the airways
Oogonia at birth: arrested in prophase I of meiosis and are called primary oocytes, arrested
cells are diploid (2n) and have 46 chromosomes
Primary oocyte: primary oocyte completes the first meiotic division within the mature follicle
shortly before ovulation-, secondary oocyte, secondary oocyte is haploid (In) and contains 23
chromosomes, it enters the second meiotic division but is arrested in metaphase II at the time
of ovulation, the secondary oocyte completes meiosis I1 during fertilization
Rotator cuff tear: common cause of shoulder pain, components of the rotator cuff include the
tendon insertions of: supraspinatus, infraspinatus, teres minor, subscapularis muscles, S/S of
rotator cuff injuries: painlweakness with active shoulder abduction
Tennis elbow: pain occurs in the area where the extensor muscle tendons insert near the lateral
epicondyle, common in: raquette sports, repetitive use of a hammer or screwdriver
Golfer's elbow: pain is located where the flexor muscle tendons insert near the medial epicondyle
Ulnar newe compression: the ulnar nerve may be entrapped in the following areas: transverse
carpal ligament, elbow ("funny bone area"), there is pain and numbness of the ulnar aspect of the
forearm and ring and little finger plus weakness of the intrinsic muscles of the hand
Compartment syndromes: increase of pressure in a confined space: pressure reduces perfusion,
which may lead to permanent ischemic contractures of the muscle (s) in that compartment, S/S of
a compartment syndrome: pain, paresthesias, pallor, paralysis, pulselessness, causes of
compartment syndromes: fractures, injuries to arteries/soft tissue, prolonged limb compression
(e.g., tight fitting cast), Volkmann's ischemic contracture: complication of a supracondylar
fiacture of the humerus; there is injury to the brachial artery and median nerve; brachial artery
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
ischemia leads to increased pressure in the closed muscle compartments of the forearm with a
subsequent decrease in venous and then arterial perfusion: this may lead to permanent ischemic
contractures of the muscle
Carpal tunnel syndrome: entrapment syndrome of the median nerve in the transverse carpal
ligament of the wrist, causes: rheumatoid arthritis/pregnancy, overuse of the hands/wrist,
amyloidosis, hypothyroidism, S/S: pain, numbness, or paresthesias in the thumb, index finger,
second finger, third finger, and the radial side of the fourth finger; thenar atrophy ("ape" hand
appearance); pain is reproduced by tapping over the median nerve
"Claw hand": ulnar nerve palsy, ulnar nerve functions: adduction of the fingers due to
innervation of the palmar and dorsal interosseus muscles; adduction of the thumb (adductor pollicis
muscle)
llWrist drop": radial nerve palsy, radial nerve functions: extensor muscles of the wrist and
digits; wrist drop refers to a hand that is flexed at the wrist and cannot be extended, injury may
be due to: midshaft fractures of the humerus; draping the arm over a park bench (called "Saturday
night palsy")
"Waiter's tip deformity": brachial plexus lesion involving C5 and C6: upper trunk injury,
clinical findings in Erb-Duchenne's palsy: birth injury of the brachial plexus with damage to
C5-C6 nerves- upper trunk injury; loss of abduction of the arm from the shoulder; inability to
externally rotate the arm; inability to supinate the forearm; absent biceps reflex; asymmetric Moro
reflex: no movement on the affected side
Klumpke's paralysis: birth injury of the brachial plexus with injury to the CrCs and TI- lower
trunk injury, paralysis of the hand, Homer's syndrome
Axillary nerve injury ( C d 6 ) : fracture of the surgical neck of the humerus, dislocation of the
shoulder joint: usually anterior dislocation; may also injury the axillary artery, patient cannot
abduct the arm to the horizontal position or hold the horizontal position when a downward force is
applied to the arm:paralysis of deltoid muscle, weakening of lateral rotation of the arm:paralysis
of teres minor muscle
Herniation of LS-Sl disc : sensory loss: lateral and posterior calf; plantar aspect of the foot,
reflex loss: Achilles' reflex (tibia1 nerve LA-S3), motor deficit: loss of plantar flexion, loss of foot
eversion (weakness of peroneus longushrevis)
Herniation of L4-Ls disc: sensory loss: dorsum of the foot, webbed space between the great toe,
reflex loss- none, motor deficit: loss of dorsiflexion of the big (great) toe due to weakness of
the extensor hallucis longus
Herniation of L3-L4 disc: sensory loss: medial leg to the malleolus, reflex loss: knee jerk
(femoral nerve L - 4 ) , motor deficit: quadriceps weakness due to weakness of knee extension;
loss of dorsiflexion of the foot due to weakness of the tibialis anterior
Superior gluteal nerve injury: causes: surgery; Duchenne's muscular dystrophy, waddling
gait: the superior gluteal nerve supplies the gluteus medius and minimus muscles; loss of abduction
of the thigh and inability to pull the pelvis down; positive Trendelenburg's sign: raising of the foot
on the injured side causes
Peroneal nerve injury: MC site of entrapment is behind the knee: common in people who cross
their legs a lot; patient has a slapping gait, motor deficits: loss of foot eversion due to weakening
of the peroneus longus and brevis muscles; loss of foot dorsiflexion due to weakening of the tibialis
anterior muscle; loss of toe extension due to weakening of the extensor digitorurn longus and
hallucis longus muscles; combined effect of all the above produces an equinovarus deformity
(plantar flexion with foot drop and inversion of the foot), loss of the ankle jerk reflex
Kyphosis in adolescents: forward bending of the spine, MCC is muscular/postural problems:
commonly seen in tall adolescents
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Scoliosis: term applied to lateral curvature of the spine, idiopathic scoliosis: usually affects
adolescent girls between 10-1 6 yrs of age; usually a right thoracic curve; forward bending causes a
paraspinous prominence on the right from a hump in the ribs due to a rotational component of the
vertebra
Test used to evaluate meniscus injuries: McMurray test: test for the medial meniscus: patient is
supine+ knee is acutely flexed+ foot is grasped and the leg is externally rotated+ knee is slowly
extended while the other hand feels the posteromedial margin of the knee joint+ a click along the
posteromedial margin indicates a medial meniscus tear: femur passes over the tear, * test for a
lateral meniscus injury: same procedure as above except the leg is rotated internally and extended-,
a click is palpated along the posterolateral margin of the joint
Location and function of the anterior cruciate ligament (ACL): ACL attaches the anterior part
of the tibia to the lateral condyle of the femur- prevents anterior movement of the tibia in relation
to the femur
Location and function of the posterior cruciate ligament (PCL): PCL extends from the posterior
part of the tibia to the medial condyle of the femur- prevents posterior movement of the tibia in
relation to the femur
Tests used to evaluate the cruciate ligaments in the knee: anterior draw test to evaluate ACL:
patient supine, hip flexed 45", knee flexed 90°+ examiner places hand on the posterior aspect of
the tibia-, anterior force is applied in neutral, external, internal direction+ positive anterior draw
test is when there is anterior displacement of the tibia, posterior draw test to evaluate PCL:
patient supine, hip flexed 45", knee flexed 90°+ examiner places hand on the anterior aspect of
proximal tibia+ posterior force is applied in neutral, external, internal direction-, positive
posterior draw test is when there is posterior displacement of the tibia
Positions the knee joint is forced into that results in injury: valgus position: angulation away
from the midline, e.g. clipping injury in football, varus position: angulation towards the midline,
medially originating force is applied to the knee
S/S of a meniscus injury: pain, knee catches, locks, or gives way when walking,
swelling/popping of the knee
Medial meniscus injury: mechanism of injury: MC internal derangement of knee joint; most
commonly part of a valgus injury (e.g., clipping in football), structures damaged: medial
meniscus; medial collateral ligament; ACL, positive McMurray's test: click on posteromedial
margin with the knee flexed, externally rotated, and slowly extended
ACL injury: mechanism of injury: MC ligament injury; tom most commonly in a valgus injury
secondary to clipping or skiing, positive anterior draw sign
PCL injury: mechanism of injury: hyperextension of the knee secondary to an anterior force
pushing the tibia in a posterior direction, positive posterior draw test
Medial collateral ligament injury: tom with valgus injuries
Lateral collateral ligament injury: tom with varus injuries
MC nerve injured with clavicular fractures: ulnar nerve
MC fracture associated with falling on the outstretched hand: Colles fracture of the distal
radius: MC fracture of the wrist; "dinner fork" deformity of the proximal radial fragment
(displaced upward and backward); second most common fracture in osteoporosis in women
MC femoral fracture: femoral neck fracture: most commonly occurs in the elderly male patient
with osteoporosis; groin or knee pain is present, complications: aseptic necrosis of femoral head
due to damage to the medial femoral circumflex artery
MC foot bone fractured after a fall from a height: calcaneus
PCR mechanism: uses DNA polymerase to break down DNA into fragments
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Q-
Nutrient and Energy Requirements in Humans
A. The normal diet provides fuel for energy, precursors from which important body components
are derived (e.g., essential fatty acids and amino acids), micronutrients (e.g., vitamins, minerals,
trace metals), and water.
B. Dietary requirements for protein, vitamins, and minerals and trace elements are specified
in terms of the recommended daily allowance (RDA). -
1. RDA represents an optimal dietary intake of nutrients that under ordinary conditions
will keep the general population in good health.
2. RDA varies with sex, age, body weight, diet, and physiological status. -
For example, RDAs for nutrients increase in childhood, pregnancy, and lactation.
C. Daily energy expenditure depends on the basal metabolic rate (BMR), thermic effect of
foods, and the degree of physical activity. -
1. BMR accounts for -60% of daily energy expenditure and refers to the energy
consumption of an individual at rest.
a. BMR reflects the energy involved in normal body functions (e.g., cardiac function,
maintaining ion pumps) and primarily depends on body weight. -r
(1) The disease is marked by pitting edema and ascites (loss of the oncotic effect of
albumin), enlarged fatty liver (decreased apolipoproteins), anemia, diarrhea (loss of
brush border enzymes), and defects in cellular immunity.
(2) There is less extreme muscle wasting than occurs in rnarasmus due to the protein-
sparing effect of carbohydrates.
Dietary recommendations:
A. The body mass index (BMI) is primarily used to determine whether a person's body weight is
in the acceptable range.
1. The BMI is the patient's weight in kg divided by the height in meters squared: BMI =
weight in kglheight m2.
2. A BMI between 20-25 kg/m2 is acceptable; 25-29.9 kg/m2 is overweight; 30-39.9 kg/m5
is obese; and, greater than 40 kg/m2is considered morbidly obese.
B. The recommended distribution of total caloric intake in a diet is 50-60% from
carbohydrates; no more than 30% from fats (ideal is < 25%); and 10-20% from proteins.
1. The BMI should be in the acceptable range (e.g., 20-25 kg/m2).
2. Fat distribution should be 10% monounsaturated fats, 10% polyunsaturated fats, and
10% saturated fats.
3. Cholesterol intake should be less than 300 mg/day.
4. Protein intake should be 0.8 kg/day
C. In order to lose weight, the total calories expended must be greater than the total intake of
calories.
1. When primarily drawing upon adipose to meet energy needs, a person loses -1 lb
whenever they expend 3,500 calories more than they consume.
2. Sample calculations using patients A and B:
a. Patient A consumes 3600 kcallday consisting of 168 g of fat, 108 g of protein, and
414 g of carbohydrates. Calculate the percentage of each of the nutrients. Is the patient
gaining, maintaining, or losing weight?
(1) Fat kcal: 168 g x 9 kcallg = 1512 kcallday; fat percent = 151213600 = 42% (too
high).
(2) Protein kcal: 108 g x 4 kcallg = 432 kcallday; protein percent = 43213600 = 12%
(normal).
(3) Carbohydrate kcal: 414 g x 4 kcallg = 1656 kcallday; carbohydrate percent =
165613600 = 46% (slightly decreased).
(4) Since the patient's calculated daily energy expenditure is 3120 kcallday (see
previous calculation), the patient is consuming more calories (3600 kcallday)
than he is expending. A net gain of 480 kcallday results in a gain of 1 lb in 7-
days (35001480 = 7.3).
b. Patient B consumes 2000 kcallday consisting of 67 g of fat, 60 g of protein, and 290
g of carbohydrates. Calculate the percentage of each of the nutrients. Is the patient
gaining, maintaining, or losing weight?
(1) Fat kcal: 67 g x 9 kcallg = 603 kcallday; fat percent = 60312000 = 30% (normal).
(2) Protein kcal: 60 g x 4 kcallg = 240 kcallday; protein percent = 24012000 = 12%
(normal).
(3) Carbohydrate kcal: 290 g x 4 kcallg = 1160 kcallday; carbohydrate percent =
116012000 = 58% (normal).
(4) Since the patient's calculated daily energy expenditure is 2040 kcallday (see
previous calculation), the patient is almost consuming (2000 kcallday) the same
number of calories she is expending and will likely maintain her weight.
Water soluble vitamins
A. Water-soluble vitamins generally fbnction as cofactors in enzyme reactions.
B. They are readily excreted in the urine, and rarely reach toxic levels.
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
3. Functions of pyridoxine
a. transamination reactions (reversible conversion of amino acids to a-ketoacids),
which are catalyzed by the transaminases alanine aminotransferase (ALT) and
aspartate arninotransferase (AST).
b. cofactor for Gaminolevulinic acid (ALA) synthase, which catalyzes the rate-
limiting reaction that converts succinyl CoA + glycine into &ALA in heme synthesis.
c. synthesis of neurotransmitters such as y-aminobutyrate (GABA), serotonin, and
norepinephrine.
d. cofactor in decarboxylation reactions (e.g., conversion of histidine to histamine),
glycogenolysis (e.g., glycogen phosphorylase), deamination reactions (e.g.,
conversion of serine to pyruvate and ammonia), and conversion of tryptophan to
niacin.
4. Pyridoxine deficiency is most commonly seen in alcoholics and in patients receiving
isoniazid therapy for tuberculosis.
Pyridoxine deficiency is also noted in countries that use unfortified goat's milk.
H. Cobalamin (vitamin BIZ;contains cobalt): in notes
I Ascorbic acid (vitamin C)
1. It is present in citrus fruits, potatoes, green and red peppers, broccoli, tomatoes, spinach,
and strawben-ies.
2. Functions of vitamin C
a. Hydroxylation of lysine and proline residues during collagen synthesis
b. Antioxidant activity (sequesters free radicals)
c. Reduces non-heme iron (+3 valence) from plants to the ferrous (+2 valence) state for
reabsorption in the duodenum
d. Keeps tetrahydrofolate ( F H 4 ) in its reduced form
e. Cofactor in the conversion of dopamine to norepinephrine in catecholamine synthesis
3. Causes of vitamin C deficiency (scurvy) include diets lacking fruits and vegetables ("tea
and toast" diet) and smoking cigarettes.
4. Excess intake of vitamin C may result in renal stone formation.
Vitamin Clinical symptoms and signs of deficiency
lliamine (B1) Wernicke-Korsakoff syndrome (confusion, ataxia, nystagmus,
ophthalmoplegia, antegrade and retrograde amnesia, precipitated
by giving intravenous with glucose), peripheral neuropathy
(dry beriberi), congestive cardiomyopathy (wet beriberi).
Riboflavin (B2) Corneal neovascularization, glossitis (magenta tongue),
cheilosis (cracking of lips), angular stomatitis (fissuring comers
of mouth).
Niacin (B3) Diarrhea, dermatitis (hyperpigmentation in sun-exposed areas),
dementia.
Pantothenic acid None described.
(Bs)
Pyridoxine ( B 6 ) Sideroblastic anemia (microcytic, anemia with ringed
sideroblasts), peripheral neuropathy, convulsions.
Vitamin Clinical symptoms and signs of deficiency
Cobalamin @I*) Macrocytic (megaloblastic )anemia (increased mean
corpuscular volume), neutropenia and thrombocytopenia,
hypersegmented neutrophils, glossitis, subacute combined
degeneration (demyelination in posterior columns and lateral
corticospinal tract), dementia, achlorhydria, atrophic
gastritis body and fundus, increased serum gastrin (only
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
* Fat-Soluble Vitamins
A. Functions: hormones, cofactors, hemostatic agents, and antioxidants.
B. They include vitamins A, D, E, and K and are absorbed with fats, transported in chylomicrons,
and stored in the liver and adipose tissue.
C. Toxicity can occur.
D. Vitamin A (retinol)
1. It is present in cod liver oil, dairy products, eggs, dark green leafy vegetables (e.g.,
parsley), and carrots.
2. Retinol (alcohol), retinal (aldehyde), and retinoic acid are the active forms of vitamin A.
a. p-Carotenes (provitamin A) found in vegetables and retinol esters in the diet are
converted into retinol, which is esterified (forming retinol esters) in the enterocytes of
the small intestine.
An excess of p-carotenes in the diet turns the skin yellow, but the sclera
remains white (unlike jaundice).
b. Retinol esters are packaged into chylomicrons and transported to the liver for
storage.
c. Retinol is released from the liver, complexes with retinol-binding protein (RBP),
and is delivered to target tissues throughout the body (except heart and skeletal
muscle).
d. In the cytosol, retinol is irreversibly oxidized to retinoic acid.
e. Retinoic acid (similar to steroid hormones and vitamin D) binds to nuclear
receptors forming a complex that activates gene transcription of protein
products.
3. Functions of vitamin A -
a. Component of the visual pigments within rod and cone cells of the retina
b. Important in normal cell differentiation and prevents epithelial cells from
undergoing squamous metaplasia y
G. Vitamin K
1. Sources of vitamin K include green lea& vegetables and bacterial synthesis of inactive
vitamin KZin the colon (50% of total amount).
a. After reabsorption in the bowel, vitamin K is oxidized in the microsomal enzyme
by an epoxidase for storage as an inactive epoxide.
b. To be catalytically active (vitamin K1), it must be reduced by the microsomal
enzyme epoxide reductase.
2. Vitamin K, y-carboxylates glutamate residues in the vitamin K-dependent
coagulation factors, which are II (prothrombin), MI,M,X, and proteins C and S.
a. The vitamin K-dependent coagulation factors are all synthesized in the liver in a
non-functional state.
b. When y-carboxylated in the liver by vitamin K1 and released into the circulation,
they have the capacity to bind to calcium and be utilized in the formation of a clot.
c. The prothrombin time (PT) is a coagulation test that evaluates all of the vitamin
K-dependent factors except factor IX and proteins C and S.
d. Coumarin-derivatives act as anticoagulants by inhibiting the activity of hepatic
epoxide reductase, hence the vitamin Kdependent factors are rendered non-
functional by their inability to bind to calcium.
- Coumarinderivatives are present in rat poison, which is a common childhood
poisoning.
3. The most common cause of vitamin K deficiency is the use of broad-spectrum
antibiotics, which destroy colonic bacterial synthesis of the vitamin. Other causes
include-
a. Therapy with coumarinderivatives: inhibits hepatic epoxide reductase
b. Fat malabsorption: cannot reabsorb fat-soluble vitamins (e.g., celiac disease)
c. Newborns: lack bacterial colonization of the bowel and must receive an intramuscular
vitamin K injection at birth to prevent hemorrhagic disease of the newborn
d. Breast milk: inadequate supply of vitamin K
4. Excessive intake of vitamin K leading to toxicity is uncommon.
5. Clinical findings associated with vitamin K deficiency and excess: see Table
3. Functions of phosphorous
a. Mineralization of bones and teeth
b. Component of DNA and RNA
c. Component of phosphorylated vitamins (e.g., thiamine, pyridoxine) and ATP
d. Traps monosaccharides in cells (e.g., phosphorylation of glucose in glycolysis)
e. Activates enzymes (e.g., protein kinase) and deactivates enzymes (e.g., glycogen
synthase)
f. Maintains pH: protons secreted into the renal tubule lumen react with dibasic
phosphorus (HF'O~~') to form monobasic phosphorus (HzPOd, which is called
titratable acidity.
4. Control of phosphorous
a. PTH has a phosphaturic effect.
b. Vitamin D (calcitriol) increases reabsorption of phosphorus in the small bowel.
5. Causes of hypophosphatemia
a. Respiratory and metabolic alkalosis: most common cause; alkalosis enhances
glycolysis and phosphorylation of glucose
b. Hypovitaminosis D due to malabsorption: decreased intestinal reabsorption of
phosphorus
c. Primary hyperparathyroidism: increased loss of phosphorus in urine
6. Causes of hyperphosphatemia
a. Renal failure: most common cause; decreased renal excretion
b. Primary hypoparathyroidism
c. Normal children: higher levels of phosphorus help drive calcium into bone
E. Sodium
1. It is the most abundant extracellular fluid cation.
2. It is primarily found in table salt.
3. Functions of sodium
a. Regulation of pH, osmotic pressure, and water movement in body fluids
The serum sodium concentration is the primary determinant of water movements
by osmosis between the extracellular and intracellular fluid compartments.
b. Maintains muscle and nerve excitability
c. Active transport of glucose, galactose, and amino acids in the small intestine
d. Maintains the diffusion potential of membranes
4. Control of sodium
a. Diet
b. Aldosterone: controls renal reabsorption (when present) and excretion (when absent)
c. Atrial natriuretic peptide: decreases reabsorption in the kidneys
5. Causes of hyponatremia
a. Thiazide and loop diuretics: most common cause; increase renal excretion
b. Inappropriate secretion of antidiuretic hormone: dilutional effect in plasma of excess
water reabsorption from the collecting tubules of the kidneys
c. Congestive heart failure and chronic liver disease: dilutional effect in plasma of
excess water reabsorbed from the kidneys
6. Causes of hypernatremia
a. Osmotic diuresis: most common cause; loss of a hypotonic salt solution in the kidneys
due to glucosuria, excess urea, or rnannitol (treatment of cerebral edema)
b. Diabetes insipidus: loss of water due to deficiency or dysfunction of antidiuretic
hormone
7. Clinical findings associated with hyponatrernia and hypernatremia: see Table
F. Chloride
1. It is the most abundant extracellular fluid anion.
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
2. Sources of chloride include meats, fruits and vegetables, legumes, and nuts.
3. Functions of chloride
a. Regulation of pH and osmotic pressure
b. Regulates neuromuscular excitability and muscle contraction
4. Control of chloride
a. Diet
b. Aldosterone: controls renal reabsorption (when present) and excretion (when absent)
5. Causes of hypochloremia
a. Thiazide and loop diuretics: increase renal excretion
b. Vomiting: lost in the vomitus
6 . Causes of hyperchloremia
a. Mineralocorticoid excess: increases both sodium and chloride reabsorption
b. Renal tubular acidosis and diarrhea: loss of bicarbonate causes an increase in chloride
to offset the loss of negative charges
G . Potassium
1. It is the most abundant intracellular cation.
2. Sources of potassium include meats, vegetables and fruits, nuts, and legumes.
3. Functions of potassium
a. Regulation of pH and osmotic pressure
b. Regulation of neuromuscular excitability and muscle contraction
c. Regulates insulin secretion: hypokalemia inhibits insulin secretion, while
hyperkalemia stimulates insulin secretion
4. Control of potassium
a. Aldosterone: controls renal reabsorption (when absent) and excretion (when present)
b. Arterial pH:
(1) Alkalotic conditions cause hydrogen ions to move out of the cell (provides
protons) and potassium into the cell (leads to hypokalemia) in order to maintain
electroneutrality.
(2) Acidotic conditions cause hydrogen ions to move into cells (for buffering) in
exchange for potassium (leads to hyperkalemia).
5. Causes of hypokalemia
a. Thiazide and loop diuretics: increase renal excretion
b. Vomiting and diarrhea: lost in the body fluids
c. Aldosterone excess: increased renal excretion
6 . Causes of hyperkalemia
a. Renal failure: MCC; decreased excretion of potassium
b. Addison's disease: due to loss of aldosterone
H. Magnesium
1. Sources of magnesium include green vegetables, nuts, and legumes.
2. Functions of magnesium
a. Calcium metabolism:
Cofactor of adenylate cyclase involved in the activation of PTH
Increases PTH synthesis and release
b. Component of bone
c. Muscle contraction: modulates the vasoconstrictive effects of intracellular calcium
d. Nerve impulse propagation
e. Cofactor in ATPases (e.g., sodium/potassium pump ATPase, calcium pump ATPase)
3. Causes of hypomagnesemia
a. Alcoholism: most common cause; increased renal loss
b. Diuretics: increased renal loss
c. Drugs (e.g., aminoglycosides, cisplatinum): increased renal loss
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
4.Causes of hypermagnesemia
a. Renal failure: decreased excretion
b. Treatment of eclampsia with magnesium sulfate
Mineral Signs and symptoms of deficiency Signs and symptoms of excess
Calcium Tetany (hypocalcemia lowers Kidney stones (calcium oxalate and
muscle and nerve threshold potential), phosphate), metastatic calcification
signs tetany: carpopedal spasm (calci-fication of normal tissues, e.g.,
(thumb adducts into palm), deposition in the kidneys is called
Chvostek's sign (facial twitch after nephrocalcinosis), polyuria (due to
taping VII nerve), muscle twitching, calcification of renal tubule basement
osteoporosis (decreased bone mass). membranes).
Phosphorous Muscle weakness, rhabdomyolysis Hypocalcemia (high phosphorous drives
with myoglobinuria (due to low calcium into bone and soft tissue),
ATP), hemolytic anemia (due to low hypovitaminosis D (inhibits activity of 1-
ATP). a-hydroxylase).
Sodium Mental status abnormalities Mental status abnormalities
(cerebral edema, water shifts into (intracellular shrinkage of neuroglial cells
cells by osmosis), convulsions. and neurons), convulsions.
Potassium Muscle weakness (cannot repolarize Heart stops in diastole (must protect
muscle), polyuria (renders heart with injection of calcium gluconate).
collecting tubule resistant to
antidiuretic hormone).
Magnesium hypocalcemia with tetany (acquired Neuromuscular depression (depressed
hypoparathyroidism due to impaired deep tendon reflexes, muscle weakness),
PTH secretion and resistance in target bradycardia.
tissue), tachycardia.
Trace elements
A. Iron
1. Primary sources of iron include meat, eggs, vegetables, and fortified cereals.
2. Iron is the structural component of heme in hemoglobin, myoglobin, and the
cytochrome oxidase system. It is also an important cofactor for enzymes (e.g., catalase).
a. Meat has heme iron, which is ferrous and ready for reabsorption in the duodenum.
Once reabsorbed by duodenal enterocytes, heme is enzymatically degraded to
release iron.
Most of the iron is diverted to storage as apoferritin in the enterocyte, while a
small amount is delivered to plasma transfenin, the circulating binding protein of
iron.
b. Plants contain non-heme iron, which is in the ferric state, hence reabsorption is
more complex and involves a number of different binding-proteins before it is
transferred to transfenin.
c. Ferritin, a soluble iron-protein complex, is the storage form of iron in the intestinal
mucosa, liver, spleen, and bone marrow.
(1) Serum ferritin levels reflect iron stores in the bone marrow.
(2) Serum ferritin is the best screening test for iron deficiency and iron overload
disorders (e.g., hemochromatosis).
d. Hemosiderin is an insoluble storage product of ferritin degradation.
(1) Hemosiderosis is an acquired accumulation of hemosiderin in macrophages in
tissues throughout the body: alcoholics and patients with a chronic transfusion
requirement are at risk for hemosiderosis.
Note: This material is copyrighted. All rights resewed. Edward Goljan, M.D. 2003
Rate limiting reaction in fatty acid synthesis: acetyl CoA carboxylase, enzyme converts
acetyl CoA into malonyl CoA
Rate limiting reaction in @oxidation of fatty acids: carnitine acyltransferase I, enzyme in
outer membrane of mitochondria removes acyl group from fatty acyl CoA and transfers it to
camitine (ac~lcarnitine), inner membrane enzyme removes acyl group from acylcarnitine and
transfers it back to CoA to produce fatty acyl CoA
Rate limiting reaction in glycolysis: phosphohctokinase I, enzyme converts fructose 6-
phosphate into h c t o s e 1,6-bisphosphate
Rate limiting reaction in gluconeogenesis: h c t o s e 1,6-bisphosphatase, enzyme converts
h c t o s e 1,6-bisphosphateto fructose 6-phosphate
Rate limiting reaction in glycogen synthesis: glycogen synthase, enzyme forms a-1,4
glycosidic linkages between a glucose unit from UDP-glucose and the non-reducing end of an
existing glycogen chain
Rate limiting reaction in glycogenolysis: liver phosphorylase, enzyme cleaves a-1,4 linkages
(releases glucose 1-phosphate) but stops working four glucose units from the branch point
Rate limiting reaction in pentose phosphate pathway: glucose 6-phosphate dehydrogenase,
G6PD converts glucose 6-phosphate to 6-phosphogluconate
Rate limiting reaction in lipolysis: hormone sensitive lipase, enzyme hydrolyzes
triacylglycerol into fatty acids and glycerol
Rate limiting reaction in urea cycle: carbamyl phosphate synthase I, enzyme converts C02+
N& + 2 ATP into carbamyl phosphate
Rate limiting reaction in pyrimidine metabolism: carbamyl phosphate synthase I., enzyme
converts 2 ATP + C02+ glutamine into carbamoyl phosphate
Rate limiting reaction in purine metabolism: glutamine-PRPP aminotransferase, enzyme
converts PRPP + glutarnine into 5'-phosphoriboysylamine
Rate limiting reaction in heme synthesis: ALA synthase, enzyme converts succinyl CoA +
glycine into 6-aminolevulinic acid
Rate limiting reaction in ketone body synthesis: HMG CoA synthase, converts acetoacetyl
CoA into HMG CoA
Lesch Nyhan: SXR with absent HGPRT, self-mutilation, hyperuricemia, mental retardation
Branched chain amino acids and maple syrup urine disease: only muscle can metabolize
branched chain amino acids, missing dehydrogenase enzyme
Functions of cholesterol: vitamin D synthesis in the skin (7-dehydrocholesterol), steroid
synthesis, cell membranes, synthesis of bile salts/acids
Acetyl CoA uses: FA synthesis, CH synthesis, ketone body synthesis, synthesis of citrate
along with oxaloacetic acid, not a substrate for gluconeogenesis
Ketone body synthesis: HMG CoA synthase is the rate-limiting enzyme, HMG CoA lyase
converts HMG CoA into acetoacetic acid, while in cholesterol synthesis, HMG CoA reductase
converts HMG CoA into mevalonic acid, 23 ATP produced for fuel
Enzyme kinetics: V, represents the maximum velocity of an enzyme reaction when all enzyme
sites are filly saturated, K, (Michaelis-Menton constant) of an enzyme represents the substrate
concentration at which the reaction velocity is one-half of Vmax (Vmax/2), Krn describes the
enzymes affinity for substrate, increased Km indicates decreased affinity of the enzyme for
substrate, decreased Kmindicates increased affinity of the enzyme for substrate
Competitive inhibitors: V, is not changed since the reaction rate is unchanged whether the
competitive inhibitor (e.g., ethylene glycol, methyl alcohol) is binding to the active site of the
enzyme (e.g., alcohol dehydrogenase) or alcohol, K,,,increases (decrease in the affinity of the
enzyme for alcohol), since the enzyme is also actively binding with ethylene glycoVmethy1 alcohol,
infusing alcohol decreases the metabolism of ethylene glycoVmethyl alcohol, hence the effect of a
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
.
anticoagulant, keratan sulfate, hyal .
mainly responsible for the negative charg
linear glycogen chain to another residue on the chain and attaching it to the chain by a a-1,6
linkage: glycogen synthetase then adds glucose residues to the new non-reducing ends on the
branches and to the old non-reducing ends, liver glycogen maintains blood glucose during the -
fasting state until its stores are depleted: gluconeogenesis is the most important factor
maintaining glucose in the fasting state, muscle glycogen is used only by muscle
Glycogenolysis: glycogenolysis occurs in the fasting state: glucagonlepinephrine activate .-
adenylate cyclase + increases cyclic AMP (CAMP); CAMP activates protein kinase A:
phosphorylation inactivates glycogen synthase; activated protein kinase A activates phosphorylase
kinase; activated phosphorylase kinase activates glycogen phosphorylase A; activated glycogen
phosphorylase A (rate limiting enzyme, muscle and liver phosphorylases) cleaves al-4bonds
up to 4 glucose residues of a branch point; glucosyl (4:4) transferase (debrancher enzyme)
removes 3 of the outer glucose residues that are left on the branch and transfers them to the non-
reducing end of another chain where glycogen phosphorylase A cleaves off more glucose 1-
phosphates; amylo- a-1,6 glucosidase (debrancher enzyme) cleaves off the remaining 1 glucose on
the chain leaving behind a free glucose: ratio of glucose l-PO4 to free glucose is -10/1; glucose 1-
phosphate + phosphoglucomutase+ glucose 6-phosphate; glucose &phosphate + glucose 6
phosphatase (gluconeogenic enzyme deficient in von Gierkels)+ glucose, small amounts of
glycogen are degraded in lysosomes by a-1,4 glucosidase (acid maltase, which is deficient in
Pompe's disease)
Von Gierke's glycogenosis: AR disease with a deficiency of glucose 6 phosphatase, a
gluconeogenic enzyme that is primarily located in the liver and kidneys, glucose is decreased in
the fasting state (fasting hypoglycemia) and glucose 6-phosphate accumulates leading to an
increased synthesis of normal glycogen primarily in the liver and kidneys (hepatoreno-
megaly), glycogen excess in renal tubules interferes with lactic acid and uric acid excretion-,
increased anion gap metabolic acidosis and increased incidence of gout, stimulation tests for
gluconeogenesis using glucagon, fructose, galactose cannot increase blood glucose owing to
the missing glucose 6-phosphatase
Pompe's glycogenosis: AR disease with a deficiency of the lysosomal enzyme a-1,4
glucosidase (acid maltase): only glycogenosis that is a lysosomal storage disease, accumulation
of normal glycogen in lysosomes in multiple organs, restrictive cardiomyopathy from glycogen
deposition in the heart is the MC COD
* McArdles disease (glycogenosis): AR disease with a deficiency of muscle phosphorylase,
muscle glycogen cannot be degraded leading to reduced amounts of glucose for muscle energy,
early fatigue with exercise (no ATP) leading to muscle cramps+ rhabdomyolysis -,
myoglobinuria, absence of lactic acid in blood after exercise, normal blood glucose: muscle
does not contribute to blood glucose, enzyme assay of muscle confirms diagnosis: compatible
with life
* Debrancher and brancher deficiencies: debrancherlbrancher deficiencies are all associated
with an accumulation of abnormal glycogen, glucosyl4:6 transferase @rancher) deficiency:
no branches on glycogen, glucosyl (4:4) transferase debrancher deficiency: increase in
a-limit dextrins (small branched oligosaccharides) and decrease in free glucose; epinephrine
challenge leads to an increase in a-limit dextrins and a decrease in free glucose, amylo- a-
1,6 glucosidase debrancher deficiency: decreased amounts of free glucose, since the remaining
glucose cannot be cleaved off
Note: This material is copyrighted. All rights r e s e ~ e dEdwai,d
. Goljan, M.D. 2003
delete A
1
5' GCC AAA GUU AUU UGG 3' frameshift mutation
Val Ile Trp
C. Tay Sachs:
(1) 4 base insertion produces a frameshift mutation
(2) codes for defective hexosaminidase
D. cystic fibrosis:
(1) 3 base deletion with loss of phenylalanine on chromosome 7: this is not a
frameshift mutation since it is a multiple of 3
lle lle Phe Gly Val
normal DNA ATC ATC T'IT GGT GTT
C F DNA ATC AT- -T GGT GTT
ATT
Ile ne Gly Val
(2) transcribes a defective CF transmembrane regulator that disintegrates in
Golgi apparatus before it goes to the cell membrane
MCC of otitis mediatsinusitis in children: Streptococcus pneumoniae
MCC of otitis externa: Pseudomonus aeruginosa- Rx with topical polymyxin B + neomycin +
hydrocortisone, also cause of malignant otitis external in diabetics
Note: This material is copyrighted. All rights resewed. Edward Goljan, M.D. 2003
Rx of choice for Chlamydia trachomatis: doxycycline (many are using a single dose of
azithromycin)
Normal microflora of nasopharynx: anaerobic bacteria: Peptostreptococcus, Fusobacterium,
Bacteroides, viridans group streptococci, coagulase negative staphylococcus, avirulent
Hemophilus and Neisseria rneningitidis species
Normal microflora of skin: MC is coagulase negative staphylococcus, less commonly:
Staphylococcus aureus, Cotynebacteria, Propionibacter (important in acne), Clostridium
perfingens (20% of healthy people), Candida, Malassezia
Receptor for HIV: CD4molecule on helper T cells (also rnacrophages, dendritic cells)
Complement fixation reactions: hemolysis of test system RBCs is a negative test, while lack of
hemolysis is a positive test
Hanta virus: carried in rodents (deer mice), ARDS, hemorrhage, renal failure, viral RNA
in lung tissue- PCR test is best overall test
Which live vaccine can be given to a patient with AIDS: MMR- MMR is given only because the
natural infection for measles is worse than the one that potentially could happen with the attenuated
virus
Live vaccines: cannot give to imrnunocompromised patients: e.g., organ transplant patient,
MMR: only one that you can give to AIDS patient, varicella, OPV, BCG, smallpox,
yellow fever
Polysaccharide vaccines: Pneumococcus, Hib- meningococcal vaccine is another example
Killed virus vaccines: influenza, rabies, SALK vaccine
Immunizations that are contraindicated in patients with anaphylactic reactions against eggs:
MMR, influenza, yellow fever
Immunizations that are contraindicated in patients with anaphylactic reactions against
neomycin: MMR, varicella- neomycin is used as a preservative
Newborn baby in HIV positive mother: newborn has anti-gp 120 in the serum (IgG antibody),
prevent HIV in newborn by giving mother A2T
Bruton's agammaglobulinemia: SXR, defect in pre-B to B cells- no germinal follicles in
nodes or plasma cells, prone to respiratory infections, Rx with N gamma globulin
SCID: combined B and T cell deficiency, first immunodeficiency treated with gene therapy:
replacement of adenosine deaminase, no germinal follicles or plasma cells, no T cells in
parafollicular area; accumulation of dATP, which inhibits ribonucleotide reductase with
subsequent decrease in deoxynucleoside triphosphate precursors for DNA which reduces the
formation of B and T cell precursors; BM transplant helpful
Wiskott Aldrich: SXR, triad sinopulmonary infections, eczema, thrombocytopenia, Bm
cell deficiency: & IgM: poor antigenic response to bacterial polysaccharide, normal IgG, ? IgA and
IgE, defects in CMI develop late, increased incidence of leukemia/lymphoma, Rx: BM
transplant
Common variable immune deficiency (CVID): no inheritance pattern, intrinsic defect in B
ceil maturation into antibody-producing plasma cells, presents between 15-35 yrs of age,
recurrent sinopulmonary infections: decreased Ig production, giardiasis, malabsorption due to
celiac sprue, all Igs decreased, Rx- IV y-globulin
Selective IgA deficiency: MC hereditary immunodeficiency, intrinsic defect in B cell
differentiation into committed B cells synthesizing IgA andlor possible T cell defect that
prevents B cells from synthesizing IgA, clinical: recurrent sinopulmonary infections: lack of
secretory Igk, giardiasis; autoimmune disease; allergies, develop anti-IgA antibodies with
exposure to blood products: danger of anaphylactic reaction when exposed to blood products
with IgA, serum and secretory IgA levels decreased
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003 .
Water loving pathogen that is most commonly seen in men over 40-years-old who are
smokers. It produces a confluent bronchopneumonia, with fever, non-productive cough,
hemoptysis and other systemic signs and symptoms. It commonly produces hyponatremia
related to development of interstitial nephritis leading to hyporeninemic hypoaldosteronism.
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
The pathogen is best visualized with direct immunofluorescence or a silver stain: Legionella
pneumophila
Respiratory pathogen with a significant mortality in those over 55 years of age and who have
underlying renal, cardiac or lung problems. It produces a severe, exudative pneumonia with a
propensity for secondary bacterial invasion. There is an association with Reye's syndrome in
children that take aspirin: influenza
Respiratory pathogen that is transmitted without a vector, unlike other pathogens in its
family group. It is primarily transmitted by inhalation by individuals who have a n association
with the birthing process in sheep, cows and goats or in those who work in the milk industry.
It is particularly common in workers who shovel feces in sheep: Coxiella burnetii
Respiratory pathogen that is transmitted by direct hand to hand transfer of infected material
and by respiratory droplet infection. Its main reservoir is school children. Development of a
vaccine is highly unlikely: rhinovims
Respiratory pathogen transmitted by droplet infection. It accounts for approximately 10% of
community acquired atypical pneumonias and a smaller percentage of cases of bronchitis.
Cold agglutinins are not associated with this pathogen. There may be an association with
coronary artery disease. It responds well to doxycycline, like other members of its family:
Chlamydia pneumoniae (TWAR)
Strict anaerobe that can produce an empyema that drains through a sinus tract out to the
skin surface. Yellow flecks of material in the drainage fluid should be Gram stained to
demonstrate its characteristic morphology: Actinomyces israelii
Pathogen that is commonly contracted in military stations and in crowded situations. It
produces an interstitial pneumonia and is often associated with erythema multiforme and
bullous myringitis. It responds well to erythromycin: Mycoplasma pneurnoniae
Respiratory pathogen that is an example of a zoonosis. It is associated with an interstitial
pneumonia. Its incidence has declined by putting tetracycline in animal feed: Chlamydia
psittaci
Predominantly a respiratory pathogen, this strict aerobe is most commonly seen in patients
with defects in cellular immunity, particularly in the setting of heart transplantation. It
produces microabscesses in the lungs, often with granuloma formation. A characteristic
feature, aside from its unusual Gram stain morphology, is that it is partially acid fast:
Nocardia asteroides
Most common cause of death in patients with cystic fibrosis: Pseudomonas aeruginosa
Most common cause of pneumonia and bronchiolitis in infants: respiratory syncytial virus
Most common cause of croup with inspiratory stridor. A lateral neck x-ray reveals a "steeple
sign": parainfluenza, tracheal obstruction
Most common cause of inspiratory stridor in a child whose lateral neck x-ray reveals the
"thumbprint" sign. Its incidence has decreased owing to the use of a vaccine: Hemophilus
influenzae
Most common cause of bronchopneumonia and lobar pneumonia in the general population:
Streptococcuspneumoniae
An executive in an office in New York City has a window air conditioner that is a favorite
roost for pigeons. She and her develop lung disease: Cryptococcus neoformans
Narrow based bud
w
An HlV positive patient with fever, night sweats, cough, dyspnea with exertion, a CD4 T
helper count of 350 cells pL, and cavitary apical lung disease: Mycobacterium tuberculosis,
note that MAI only comes when the helper T cell count is < 100 cells/pL
Most common fungal infection in an HTV positive patient: candidiasis
Most common cause of recurrent pneumonia in a patient with AIDS: Streptococcus
pneumoniae
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
On a trip to the Far East, a man develops a high fever associated with bradycardia, absolute
neutropenia, and splenomegaly. A blood culture is positive for a gram negative organism:
Salmonella typhi
28-yr-old man presents with diarrhea with mucus and blood. A stool for fecal leukocytes
reveals blood and neutrophils. Pseudomembranes are noted in a colonoscopy: could be-
Shigella sonnei, Campylobacterjejuni
Patient with AIDS develops diarrhea with steatorrhea. A biopsy reveals macrophages with a
foamy cytoplasm.: Mycobacterium avium-intraceflularewith Whipples-like syndrome
Odynophagia in a HIV positive 28-year-old man with white plaque-like material on his
tongue and buccal mucosa that scrapes off and leaves a bloody base: Candida albicans
Elevated serum amylase associated with meningoencephalitis: paramyxovirus infection
(mumps)
Gastrointestinal lymphomas arising from mucosa associated lymphoid tissue (MALT) in the
stomach: Helicobacterpylori
Most common invasive enterocolitis that commonly simulates ulcerative colitis and
pseudomembranous colitis: Campylobacterjejuni
Most common cause of diarrhea in children during the winter months that has an ELISA test
for aid in its diagnosis: rotavirus
Common cause of diarrhea in AIDS and most common cause of biliary tract disease and
pancreatitis in AIDS: cytomegalovirus
Most common cause of gastroenteritis in adults: Norwalk virus
Most common cause of a secretory diarrhea when outside the United States: Enterotoxigenic E.
coli
Most common cause of a microangiopathic anemia, thrombocytopenia, and renal failure in
children: Enterohemon'hagic E. coli- serotype 0157:H7
Elderly patient develops diarrhea a week after being treated for pneumonia while in the
hospital. A flexible sigmoidoscopy reveals a gray-yellow exudate in the rectosigmoid:
Clostridium difficile- Rx with metronidazole
Common causes of dysentery and hemolytic uremic syndrome in children: Shigella sonnei and
Enterohemon'hagic E. coli
Most common cause of non-typhoid enteric fever and cause of osteomyelitis in patients with
sickle cell disease: Salmonella paratyphi
Transmitted by a human carrier and produces a disease associated with fever, sepsis,
vasculitis, diarrhea, hepatosplenomegaly, and gallbladder disease. I t is not the most common
cause of osteomyelitis in children with sickle cell disease: Salmonella typhi
MC organism contaminating blood transfusions and may be associated with triggering
ankylosing spondylitis: Yersinia enterocolitica
Produces obstruction of the terminal ileum: Mycobacterium tuberculosis, swallowed
organisms fiom a primary in the lungs
Invasive helminth that is often disseminated in AIDS patients and a common cause of
autoinfection and superinfection: Strongyloides stercoralis
Type (s) of hepatitis with no protective antibodies: Hepatitis C and D
Type (s) of hepatitis with no chronic state: Hepatitis A and E
Most common type of hepatitis found in day care centers: Hepatitis A
Most common type (s) of hepatitis leading to hepatocellular carcinoma: Hepatitis B and C
Most common hepatitis associated with polyarteritis nodosa: HBV
Most common hepatitis in traveler's to places outside the United States: Hepatitis A
Most common hepatitis in jails and corrective institutions: Hepatitis A
Most common sexually transmitted types of hepatitis: Hepatitis A, B, C
Most common cause of posttransfusion hepatitis and chronic hepatitis: Hepatitis C
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Most common type (s) of hepatitis prevented by immunization with hepatitis B vaccine:
Hepatitis B, D, also prevents hepatocellular carcinoma fiom HBV cirrhosis
Most common type (s) of hepatitis transmitted parenterally: Hepatitis B, C, D
Most common type (s) of hepatitis with protective antibodies: Hepatitis A, B, and E
Most common hepatitis producing fulminant hepatitis in a patient with a pre-existing
hepatitis: Hepatitis D: requires HBsAg to infect hepatocytes
Most common type (s) of hepatitis transmitted by the fecal-oral route: Hepatitis A and E
Most common type of hepatitis in homosexuals: Hepatitis A: unprotected.ana1intercourse
Most common type (s) of hepatitis that may lead to chronic hepatitis: Hepatitis B, C, D
Most common type of hepatitis associated with cryoglobulins and membranoproliferative
glomerulonephritis: Hepatitis C
Most common type of hepatitis transmitted by accidental needle stick: Hepatitis B
Most common cause of spontaneous bacterial peritonitis in adults with cirrhosis and ascites:
E. coli, Streptococcus pneumoniae is MCC in ascites associated with nephrotic syndrome in
children
Pathogen associated with inguinal lymph nodes containing granulomatous microabscesses
and localized lymphedema and rectal strictures as a complication: Lymphogranuloma
venereum- only STD without ulcers
32-year-old woman complains of a vaginal discharge that has a 'fishy odor'. I t is particularly
noticeable during coitus. The discharge has a pH of 5. Examination of the discharge shows
bacteria adhering to epithelial cells: Gardnerella vaginalis- clue cells, not an STD, only Rx
the patient with metronidazole
35-year-old diabetic presents with a vaginal discharge that is thick and has the appearance of
cottage cheese: Candida albicans- Rx with fluconazole
32-year-old female presents with intense vulvar pruritus. She has a purulent malodorous
frothy green vaginal discharge. The discharge can be wiped from the wall of the vagina and
leaves patchy vaginal erythema (strawberry vagina). The pH of the discharge is 5.6:
Trichomonas vaginalis- Rx both partners with metronidazole
Most common cause of neonatal meningitis. Causes chorioamnionitis due to an ascending
infection from the vagina and cervix. Risk of infection of neonate is greater when there is
premature rupture of the membranes prior to delivery: group B Streptococci (Streptococcus
agalactiae)
23-year-old woman on the third day of menses presents with fever, severe lower abdominal
pain and adnexal tenderness with movement of the cervix. History reveals sexual intercourse
3-4 days prior to menses: Neisseria gonorrhea- the short incubation period is most consistent
with GC rather than Chlamydia, she has PID and should be treated with cefhiaxone and
doxycycline, the latter to cover possible Chlamydia trachomatis as a coinfection
34-year-old patient has had an IUD (intrauterine device) in place for 9 months as a method of
birth control and now complains of vaginal discharge. At the request of the patient, the IUD is
removed. Yellow flecks of material are attached to the IUD which on Gram stain reveal a
filamentous gram positive bacteria: Actinomyces
46-year-old woman presents with dysuria, increased frequency, and a mucopurulent vaginal
discharge. Vaginal smears of the exudate and examination of the urinary sediment are
negative for organisms but show many leukocytes. Her last sexual exposure was 10 days ago:
Chlamydia trachomatis
32-yr-old woman has a painful ulcer on the left labia majora and ipsilateral painful inguinal
lymph nodes. A gram stain from the base of the ulcer reveals gram negative rods in a "school
of fish" orientation: Hemophilus ducreyi
25-yr-old woman has a painless ulcer on the left labia majora and ipsilateral painful inguinal
lymphadenopathy: Treponemapallidum- primary syphilis.
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
23-yr-old woman develops fever, painful lymphadenopathy, and painful vesicles on her
external genitalia that later ulcerate. A Tzanck prep from the base of one of the ulcers is
positive: Herpesvirus type 2- note how primary infection is systemic
23-yr-old sexually active woman is noted to have fern-like lesions around the labia and
perianal area. Her RPR is negative: human papilloma virus- the patient has condyloma
acuminata, or venereal warts
30-year-old ornithology graduate student presents with altered mental status, stupor, and
headache. There is no nuchal rigidify. He has been studying marsh birds over the last month
in a mosquito-infested swamp area in the Midwest. A gram stain and culture of the CSF is
negative: patient has an arborvirus type of encephalitis
18-year-old Navy recruit presents with fever, headache, and a positive Kernig's test. He is the
10th case in the past week that has occurred at the base: the patient has meningitis, most likely
Neisseria meningitidis based on the crowded conditions
32-year-old man renal transplant patient who is immunosuppressed has a positive India ink
preparation: cryptococcal meningitis
Bilateral ophthalmia neonatorum during the first week: N. gonorrhoeae, transmitted on the
way through the cervix
Granulocyte colony stimulating factor (GCSQ: produced by fibroblasts, stimulates
neutrophil developmerit in the bone marrow
Granulocyte/macrophage colony stimulating factor (GM-CSQ: produced by macrophages
and T cells, stimulates neutrophil 'and monocyte development in the bone marrow
B cells: 10-20% of total lymphocyte count, markers: intracytoplasmic p heavy chains: pre-B
cell: surface p and 6 heavy chains: mature B cell and antigen recognition site, function: antibody
synthesis, surface receptors: IgG Fc receptor, CD21 for EBV, testing: B cell count: flow
cytometry; immunoglobulin concentration: order of decreasing concentration IgG, IgA, IgM, IgD,
and IgE; detect isohemagglutinins; mitogen stimulation: pokeweed
T cells: 60-70% of total lymphocyte count, markers: monoclonal antibody marker studies for
cluster designation (CD) types; immature T cells have nuclear enzyme terminal deoxynucleotidyl
transferase (tdT) on their surface, functions: type IV hypersensitivity; cytokines regulate B cells;
defense against intracellular pathogens (e.g., TB, protozoa), testing: mitogen assays: functioning
T cells are specifically activated by phytohemagglutinin and concanavalin A; skin tests to evaluate
cellular immunity: Candida is the main antigen used; absence of an immune indicates anergy or a
lack of cellular immunity (e.g., AIDS)
Mode of transmission of HIV in the United States in descending order: receptive anal
intercourse between men, vaginal intercourse male to female: infected semen has more surface
area to infect, female to male: less surface area in male urethra to infect
Positive enzyme immunoabsorbent assay (EM)test for HIV in a newborn: due to
transplacental transmission of the IgG antibody fiom the infected mother, document HIV
infection in newborn by detection of HIV RNA by PCR (best test) and p24 antigen capture assay
AIDS testing with enzyme immunoabsorbent assay (EIA): initial screening test, detects
anti-gpl20 antibody: sensitivity 99.5-99.8%; poor specificity due to low prevalence of HIV
positivity in the general population
AIDS testing with western blot: confirmatory test for indeterminate or positive ELA, positive
western blot: presence of p24 and gp41 antibodies and either gp120 or gp160 antibodies; combined
positive predictive value of a positive EWwestern blot is 99.5%
AIDS tests for monitoring immune status: CD4 T helper cell count, HIV RNA by PCR: best
overall test to monitor viral burden
Non-AIDS defining infections: oral thrush, oral hairy leukoplakia (EBV glossitis), shingles
(H zoster), m ~ l l u ~ c ucontagiosum
m (poxvirus)
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Diagnosis of AIDS: HIV positive plus: CD4 T helper cell count: <200 cells/@; specific
malignancies: e.g., Kaposi's sarcoma; specific infections: e.g., P. carinii pneumonia (MC AIDS-
defining disease)
AIDS miscellaneous infections: bacillary angiomatosis: due to Bartonella henselae: identify
with silver stains; simulates Kaposi's sarcoma, recurrent bacterial pneumonia: Streptococcus
pneumoniae; infections encountered with CD4 T helper count 100-200 cellslpL; M C COD in
AIDS, infections encountered with CD4 T helper count 4 0 0 cells/@: disseminated MAI:
usually <75 cells/@; Candida esophagitis; CMV retinitislesophagitis; Toxoplasma encephalitis;
C~ptosporidiosis:diarrhea; cryptococcal meningitis
Transplantation success requirements: AJ3O blood group compatibility: most important test,
absence of preformed anti-HLA cytotoxic antibodies in the recipient's serum, close matches for
HLA-A, B and D loci between recipient and donor
Lymphocyte crossmatch: screens for recipient anti-HLA antibodies against donor lymphocytes
Lymphocyte microcytotoxicity test: identifies HLA-A and B derived class I antigen profiles on
recipient and donor lymphocytes using known test sera
Mixed lymphocyte reaction: used for class II antigen (D loci) matching, hctional
lymphocytes from the recipient and previously irradiated (killed) donor lymphocytes are mixed
together with tritiated thymidine to detect the degree of compatibility between their D loci-
increased radioactivity indicates incompatibility, * recipient's lymphocytes are irradiated (killed)
and hnctional donor lymphocytes are reacted against the host's HLA-D loci to check for a graft
versus host reaction (GVH)
Transplant donors: siblings are best source- chance of a sibling having another sibling with a 0,
1, or 2 haplotype match is 25%, 50%, and 25%, respectively, parents are automatically a 1
haplotype match
Graft types: autograft transfer of tissue from self to self; best survival, syngeneic graft
(isograft)- graft between identical twins, allograft- graft between unrelated individuals,
xenograft transplant of tissue from one species to another; e.g., pig heart transplant
Corneal transplants: best overall allograft survival rate
HLA haplotypes and disease: familial predisposition to disease: weak penetrance; disease is not
invariable; usually requires exposure to an environmental factor (e.g., virus), HLA-A3:
hemochromatosis, HLA-B8IDR3: celiac disease, HLA-B27: ankylosing spondylitis, HLA-
DR2: multiple sclerosis, HLA-DR3IDR4: type I insulin-dependent diabetes mellitus, HLA-
DR4: rheumatoid arthritis
Examples of type I hypersensitivity reactions: atopy: familial predisposition (multifactorial
inheritance) to develop an allergic reaction, examples: eczema (face, flexorlextensor surfaces);
hives; seasonal conjunctivitis; seasonal rhinitis; asthma, hypersensitivity to bee/wasp/homet stings:
Rx of anaphylactic reactions- sc. administration of aqueous epinephrine 1:1000 dilution
Examples of type I1 cytotoxic hypersensitivity reactions: involves antibody reactions with or
without complement, examples- Goodpasture's syndrome: anti-glomerular/pulmonary capillary
basement membrane antibodies, warm autoimmune hemolytic anemias and cytopenias,
RhlABO hemolytic disease of newborn, cells/helminths coated by specific IgGAgE antibodies,
respectively (without complement) are destroyed by cells (e.g., NK cells/eosinophils, respectively)
with low affinity IgGIIgE Fc receptors, myasthenia gravis: anti-acetylcholine receptor antibodies,
Grave's disease: IgG thyroid-simulating Ig directed against TSH receptor
Examples of type I IC immunocomplex (IC) hypersensitivity reactions: circulating ICs (antigen
+ IgGJlgM) deposit in target tissue (e.g., glomerulus, small vessel)+ activate complement
system+ chemotactic agents recruit neutrophils/macrophages that damage the tissue,
pathogenesis of localized IC reactions (Arthus reactions)- first antigen exposure results in antibody
Note: This material is copyrighted. All rights resewed. Edward Goljan, M.D. 2003
Antidotes used in unconscious patients: dextrose- RIO possible hypoglycemia from insulin
overdose, a naloxone- possible opiate overdose, intravenous thiamine- glucose may precipitate
Wernicke's encephalopathy in alcoholics with thiamine deficiency
Intravenous drug abuse (IVDA): MC localized infection is skin abscesses due to
Staphylococcus aureus, HBV MC systemic infection, HIV, infective endocarditis: MC
tricuspid and aortic valve; S. aureus MCC, tetanus: complication of "skin popping"
Heroin: a derived from poppy plant, usually "cuty' with some agent (e.g., quinine, talc)-
granulomatous reactions occur in skidungs from the cutting agents, non-cardiogenic --
pulmonary edema: frothing from the mouth is common, a focal segmental glomerulosclerosis:
hypertension + nephrotic syndrome, Rx: naloxone, a morphine derivative with a high affinity for
opioid binding sites of the mu receptor type
Meperidine: MC DOA in health professionals, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydro-
pyridine (MPTP): by-product of attempted synthesis of meperidine; produces irreversible
Parkinson's: cytotoxic to neurons in nigrostriatal dopaminergic pathways
Cocaine: MC COD from DOA in United States, MOA: blocks uptake of neurotransmitters
dopaminelNOR by presynaptic axon, predisposes to: sudden death; acute myocardial infarction
(AMI); stroke; pulmonary edema; ventricular arrhythmias; myocarditis, S/S: hypertensionlsinus
tachycardia, psychosis/seizure activity, mydriasis
Amphetamines: MOA: release catecholamines from presynaptic terminals, examples of
amphetamines: dextroamphetamine: Rx obesity; methylphenidate: Rx ADHD and narcolepsy;
methamphetamine: "ice" is street form of the drug, hallucinations: drug that most simulates
schizophrenia
Marijuana: MC illegal DOA used in United States, MOA: contains the psychoactive
stimulant A9-tetrahydrocannabinol (THC); THC binds to receptors in substantia nigra, globus
pallidus, hippocampus, cerebellum; derives from leaveslflowering tops of hemp plants (Cannabis
sativa); hashish is extracted resin of marijuana that has 5-10 times the potency of the parent
compound; high lipid solubility: THC is present in urine for more than a week, a clinical
uses: cancer: decrease N N in cancer patients; lower intraocular pressure in glaucoma; analgesia, a
S/S of marijuana use: reddening of conjunctiva; euphoria; delayed reaction time: engineer
driving a train involved in a crash with an oncoming train was found to have THC metabolites in
his urine
LSD (lysergic acid diethylamide): MOA: ergot alkaloid that binds to Dt dopamine receptors
in the brain; also blocks 5-HT2 serotonin receptor in peripheral tissue, predisposes to
chromosomal breakage leading to congenital defects, S/S of LSD toxicity: hallucinations;
flashbacks
PCP (phencyclidine): angel dust, MOA: reacts with opioid-like sigma receptors and
subtypes of glutamate receptors (antagonist); initially introduced as a dissociative anesthetic:
separates bodily functions from the mind without a loss of consciousness, S/S of PCP
toxicity: agitationlviolent behavior; coma with the eyes open; impervious to pain
Use of kblocker in Rx of Grave's disease: thyroid hormones normally upregulate synthesis of
P-receptors that interact with catecholamines and produce many of the symptoms of thyrotoxicosis,
giving P-blockers, blocks the P-receptors, hence blocking the adrenergic symptoms of
thyrotoxicosis
Electrolyte changes when giving insulin: drives glucose into the cell along with potassium and
phosphate
Central and nephrogenic DI: both have low UOsm and increased POsm, central DI shows >
50% increase in UOsm with administration of vasopressin, nephrogenic DI shows <SO% increase
in UOsm with vasopressin
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
Proximal tubule: carbonic anhydrase inhibitor- blocks reclamation of bicarbonate, which is excreted as
NaHC03 or KHC03: +proximal renal tubular acidosis, +loss of K' and ~ a +
Ascending tubule: loop diuretic- blocks Na+/K+/2crcotransport pump: +impairs generation of free water,
+calcium is also lost in the urine (Rxof hypercalcemia), + hyponatremia, hypokalemia, metabolic alkalosis,
thiazide diuretic- blocks ~ a + / c lpump:
- +allows calcium reabsorption with the help of parathormone (useful
in calcium stone formers), + hyponatremia, hypokalemia, metabolic alkalosis
DistaUcollecting tubule: spironolactone- blocks aldosterone (A) pumps: +blocks Na'/K' exchange pump,
+blocks H'/K' ATPase exchange pump, +K+ sparer, +normal anion gap metabolic acidosis
Graph of pH, PCO, bicarbonate: PC02 40 rnrn Hg is normal, bicarbonate 24 rnEq/L is normal
I b
7.0 7.40 7.8
Arterial pH
a patient A- acute respiratory acidosis with very little bicarbonate compensation, patient B-
chronic respiratory acidosis where there is more compensation by increasing bicarbonate (metabolic
alkalosis) and pH comes closer to normal range, patient C- metabolic alkalosis where there is
compensation by increasing PC02 (respiratory acidosis) patient D- metabolic acidosis where
there is compensation by decreasing PC02 (respiratory alkalosis), patient E- acute respiratory
alkalosis where there is very little drop in bicarbonate for compensation (metabolic acidosis), a
patient F- chronic respiratory alkalosis where there is good compensation by dropping bicarbonate
(metabolic acidosis) and pH is closer to normal
Q
Creatinine clearance (CCr): creatinine clearance formula: CCr = UOsm x V / POsm, where V =
volume of a 24 hr urine collection in mL/min, creatinine is not a perfect clearance substance, a
causes of a decreased CCr: increasing age; inadequate 24 hr urine collection: decreases urine
volume in the numerator; renal failure, causes of an increased CCr: normal pregnancy: increase
in plasma volume increases GFR and CCr; early diabetic nephropathy: hyaline arteriolosclerosisof
efferent arteriole
. PEN^' (fractional excretion of sodium): u s e l l in the workup of oliguria- FENa' = (UNa' x
PCr) / (PNa' x UCr) x 100, values < 1 indicate intact tubular function, values > l(usual1y > 2)
indicate tubular dysfunction
Myocardial physiology: cardiac hypertrophy increases wall stress, sinus tachycardia reduces
filling of the coronary arteries, increasing heart rate raises myocardial oxygen consumption-
cardiac muscle uses P-oxidation of fatty acids for energy, * venoconstriction- increases preload
alone, restrict salt and water intake- decreases preload alone, increase cardiac contractility- no
change in preloadfafterload
Normal gas physiology at the tissue level: C02 derived from tissue enters the RBC and
combines with H20 via carbonic anhydrase to form H2C03, H2C03dissociates into H+ and HC03-
the latter leaving the RBC in exchange for C1- anions, H+ combines with oxygenated Hgb (Hgb-
02), which releases O2 (Bohr effect), O2 leaves the RBC, dissolves in plasma and increases
capillary PO2
Q-
Normal gas physiology at the pulmonary level: Alveolar O2 diffuses into the plasma of the
pulmonary capillary owing to a greater partial pressure of alveolar 0 2 , O2 enters the RBC and
combines with ferrous ions on deoxyhemoglobin to form oxyHgb and H', HCO; enters the RBC
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003
from the plasma and combines with H+ to form H2C03, C1- anions leave the RBC to
counterbalance the entry of HCO3-, H2C03 dissociates into C02 and H2O; C02 leaves the RBC
and dissolves in the plasma to increase the PC02, which enters the alveoli for excretion
Important anatomical considerations for urine control: urogenital diaphragm: muscles of the
urogenital diaphragm are the deep transverse perineal and sphincter urethra muscle; location of the
urogenital diaphragm on a cystourethrogram is just distal to the prostate in a male; location of the
urogenital diaphragm on a cystourethrogram in a female is the beginning of urethra where it exits
the bladder, functions of the detrusor muscle: relaxed: storage of urine in the bladder;
contracted: emptying of bladder, functions of the sympathetic in bladder control: relaxes the
detrusor muscle: aids in urine storage in the bladder; contracts internal sphincter: increases urine
storage, functions of the parasympathetic system: contracts the detrusor muscle: empties the
bladder; relaxes the internal sphincter muscle by blocking sympathetic inhibition: allows emptying
of the bladder
Major vehicle for carrying C 0 2 in blood: bicarbonate (-70%)
Volumeslcapacities not directly measured by spirometry: residual volume (RV): volume of
air left over after maximal expiration, total lung'capacity (TLC): amount of air in a hlly
expanded lung, measured with a nitrogen or helium dilution method, functional residual
capacity (FRC): total amount of air in the lungs at the end of a normal expiration (end of the tidal
volume [TV]), obtained by a helium dilution technique or body plethysmography
Forced vital capacity (PVC), forced expiratory volume in 1 second (FEV1sec) and
FEVlSec/FVC: FVC is the total amount of air expelled after a maximal inspiration: the RV is what
is left over at the end of maximal expiration: normal FVC is 5 liters, forced expiratory volume in
1 second (FEVlsec):FEVlsecis how much air a person can expel from the lungs in 1 second after a
maximal inspiration, normal FEVl, is 4 liters, ratio of FEVI,,,/FVC is normally 0.80: 4 liters15
liters = 0.80, peak expiratory flow meter: outpatient method of evaluating forced vital capacity
(FVC), commonly used by asthmatics to evaluate their airways
Method of measuring RV: subtract the expiratory reserve volume (ERV) from the finctional
residual capacity (FRC), ERV is the amount of air forcibly expelled at the end of a normal
expiration (end of the TV), FRC = ERV + RV, therefore, RV = FRC - ERV
Diffusion capacity (DLco): DLco is the method of measuring the ability of a gas to difhse
through the alveolarlcapillary interface: utilizes carbon monoxide (CO), DLco is primarily
dependent on the following parameters: CO reaching the alveoli (decreased due to V/Q
mismatches: e.g., atelectasis, COPD), CO crossing the alveolar/capillary interface (decreased due to
pulmonary fibrosis or fluids in the interface)