You are on page 1of 60

Note: This material is copyrighted. All rights reserved. Edward GoUan, M.D.


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
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
Positive test (TP) 100 (Fp) 20
- Negative test (FN) 0 (TN) 80
Sensitivity of ANA: TP / TP + FN = 100 / 100 + 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)
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
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

Specificity: TN / TN + FP = 100 /I00 + 0 = 100%

Sensitivity: TP 1 TP + FN = 30 / 30 + 70 = 30%
4. P V in a test with 100% specificity- PV- may be a TN or FN- * it does not exclude
-7 e.g., anti8m is negative in a patient- * does not exclude SLE, * use other tests to
confirm SLE if your suspicions are high- e.g., antidouble stranded DNA
Positive anti-Sm (TP) 30 (Fp) 0
Negative anti-Sm (FN)70 (TN) 100
P V - = T N / T N + F N = 1001 100+70=59%
w How to calculate the reference interval of the test when given the mean of the test and 1 SD
(standard deviation):
1. remember to double the SD- 2 SD covers 95% of the normal population
2. example-
A. mean of the test = 100 mg/dL and 1 SD = 5 mg/dL (2 SD = 10 mg/dL)
B. reference interval = 90-1 10 mgldL (100 - 10 = 90 and 100 + 10 = 110)
3. for each test, 5% of normal people will have test results outside the reference interval-
A. chance of a FP increases when more than one test is ordered on a patient
B. example, 2 tests on a patient increases the chance of a FP test result on one of those
tests to -10%
4. SD is a marker of the precision (reproducibility) of the test- it is not a marker of how
accurate the test result is

Accuracy: good
Precision: good Precision: good

Effect of test sensitivity/specificity of a test on prevalence:

1. test with highest sensitivity (not specificity) increases prevalence of disease (number of
people in a population that have disease)-
A. it detects more people with the disease since it is a good screening test
B. tests with high specificity confirm disease and help differentiate a TP from a FP but
they are poor screening tests
Effect of increasing the upper limit of normal of a test reference interval (e.g., raising a
reference interval of 0-4 ng/mL to 0-10 ng/mL) on sensitivity, specificity, PV,and PV:
1. increases specificity and positive predictive value-
A. higher values are more likely to represent TPs than FPs
B. specificity always increases, which automatically increases PV+
2. decreases sensitivity and negative predictive value (PV-
A. increasing specificity of a test always decreases its sensitivity and PV-
B. FN rate increases, since more people with disease are encountered as the reference
interval increases
C. a normal test result is more likely to be a FN rather than a TN
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

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
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

* Example of a calculation for sensitivity, specificity, PV+, PV-, and prevalence:

Disease No Disease

Positive test (TP) 60 @p) 40

Negative test 20 (TN) 80

Sensitivity of the test: TP 1TP + FN = 60 I 80 = 75%

Specificity of the test: TN 1TN + FP = 80 I 120 = 66%
PV-: TN I TN + FN = 80 I 100 = 80% (80% chance it is a TN and a 20% chance it is a FN)
PV:Tp / TP + FP = 60 I 100 = 60% (60% chance it is a TP and 40% chance it is a FP)
Prevalence: TP + FN I TP + FN + TN + FP = 80 1200 = 40%
* Normal changes in pregnancy:
1. greater increase in plasma volume than RBC mass-
A. decreases hemoglobin (Hb) and hematocrit (Hct): dilutional effect
B. increases glomerular filtration rate (GFR) and creatinine clearance (CCr): due to
increased plasma volume
C. decreases serum BUNIcreatinineluric acid: dilutional effect + increased clearance
2. increased alkaline phosphatase- placental origin
3. respiratory alkalosis- estrogedprogesterone effect on CNS respiratory center causing
increased clearance of CO2 per breath
4. increased Tqand cortisol-
A. increased synthesis of their respective binding proteins
B. free hormone levels are normal
C. no signs of hyperthyroidismthypercortisolism
D. e.g., normal serum TSH and ACTH, respectively
* Newborn: high hemoglobin (Hb) due to increase in HbF-
1. left shifts oxygen dissociation curve (ODC): causes tissue hypoxia+
2. stimulus for erythropoietin (EPO) release+
3. increases RBC production with subsequent increase in Hb concentration
GI= Children:
1. increased serum alkaline phosphatase (ALP)-
A. 3-5 times higher than adults
B. osteoblasts release enzyme when stimulated by vitamin D
C. ALP increases bone mineralization
2. increased serum phosphate- required to drive calcium into bone
3. slight decrease in hemoglobin concentration when compared to adult levels
GI= Main laboratory difference in adult male and female:
1. iron studies are all lower in women- e.g., serum iron and ferritin
2. lower Hb concentration in women
Changes in old age:
1. renal changes- decrease in GFR and CCr
2. slight increase in alkaline phosphatase- due to reactive bone formation in osteoarthritis
3. slight decrease in Hgb concentration in males- due to decrease in androgens (normal
values are those of a female)
* Analytes increased with hemolyzed blood sample secondary to venipuncture:
1. LDH-
A. LDH, isoenzyme fraction is primarily increased and is greater than LDH2 isoenzyme
fraction (LDHI/LDH2flip)
Note: This material is copyrighted. All rights resewed. Edward Goljan, M.D. 2003

B. false positive acute myocardial infarction

C. LDHI isoenzyme is also in cardiac muscle


Normal LDH isoenzymes

Acute myocardial infarction: LDHI/LDH2flip

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

D. HMG CoA+ acetoacetic acid: increase in NADH converts it into P hydroxybutyric

acid (P-OHB)
4. increase in fatty acid synthesis- due to the increase in acetyl-CoA
5. hyperuricemia- lactic acidketoacids compete with uric acid for excretion in the kidneys
6. increased anion gap metabolic acidosis- lactate + P-OHB
Laboratory test alterations in smokers:
1. respiratory acidosis- air gets in but cannot get out, so C 0 2is retained
2. hypoxemia (low Pa02)- increase in PC02 always causes a decrease in PO2
3. decreased O2 saturation- decrease in Pa02 always decreases SaOz
4. increased carbon monoxide (CO) levels- CO is present in cigarette smoke
5. secondary polycythemia- low Pa02 stimulates erythropoietin release and an increase in the
production of RBCs
6. absolute neutrophilic leukocytosis- metabolites in smoke mobilize the neutrophil
marginating pool in the circulation by decreasing leukocyte adhesion to endothelial cells
Lyon's hypothesis:
1. one of the 2 X chromosomes in a female is randomly inactivated- -50% X
chromosomes are maternal, -50% X chromosomes paternal, inactivated X chromosome
becomes a Barr body- projection from the nucleus counted in squamous cells obtained by
scrapings from the buccal mucosa
2. normal females have 1 Barr bodv and normal males do not have Barr bodies
3. male with Klinefelter syndrome (XXYgenotype) has 1 Barr body
4. female with Turner's syndrome (XO) has no Barr bodies
Q= Trinucleotide repeat disorders: progressively worse disease occurs in future
generations (phenomenon is called anticipation), constant repetition of 3 nucleotide bases (e.g.,
CAG, CAG, CAG etc.), more trinucleotide repeats are added each generation leading to
progressively worse disease and earlier manifestation of the disease, examples- Huntington's
disease (AD), fragile X syndrome (SXR, female camers with trinucleotide repeats eventually
become symptomatic), Friedreich's ataxia (AD), myotonic dystrophy (AD)
* Nondisjunction: cause of the majority of chromosome number disorders (e.g., trisomy 21,
Turner's XO), due to unequal separation of chromosomes in first phase of meiosis
* Mosaicism: nondisjunction of chromosomes in mitotic division in the early embryonic period,
two chromosomally different cell lines are derived from a single fertilized egg, most cases involve
sex chromosomes- e.g., gonadal dysgenesis with XOfXX, XOKY
Translocation: one part of a chromosome is transferred to a non-homologous or homologous
chromosome, called a balanced translocation if the translocated fragment is functional,
Robertsonian translocation in Down syndrome: type of balanced translocation with a
reciprocal translocation between 2 acrocentric chromosomes (-), usually chromosomes
21 and 14, produces 1 long chromosome (14.21): extremely small translocated chromosome
usually lost, mother has the translocation: 45 chromosomes with 1 long #14.21, 1 normal #14,
and 1 normal #21, mother is normal, since both translocated fragments are functional, Down
child receives 1 normal #21 from uninvolved parent (father) and 1 14.21 and 1 normal #21 from
affected mother for a total of 46 chromosomes but all 3 #21s are functioning

parent: 45 chromosomes Down syndrome: 46 chromosomes

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
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-
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
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:

Q= Example of a pedigree with incomplete penetrance:


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:
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


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

* Multifactorial (polygenic) inheritance: l multiple small mutations plus the effect of

environment- * should be suspected when there is an increased prevalence of disease among
relatives of affected individuals, * parents and offspring have 50% of their genes in common, l
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

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
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

w Teratogen diethylstilbestrol (DES): mothers received DES to prevent threatened abortions,

DES interferes with the development of miillerian structures in female fetus causing abnormalities
in the tubes, uterus, cervix, upper one-third of vagina, female siblings: * vaginal adenosis is the
MC abnormality and is the precursor of clear cell adenocarcinoma of the vagina/cervix, cervical
incompetence- increased incidence of spontaneous abortions, uterine abnormalities- problems
with implantation, fallopian tube abnormalities- fertility problems
Fetal alcohol syndrome and teratogenic effects in newborns: MC teratogen in United
States: 2: 1000 live births, clinical- * mental retardation (MC abnormality), * intrauterine growth
retardation, * maxillary hypoplasia, * microcephaly, * atrial septa1 defects (least common finding),
* hypoglycemia at birth
Teratogen heroin: small for gestational age, initabilityhyperactivity, high pitched cry with
excessive hunger, salivation, sweating, tremors, fist sucking, temperature instability, seizures
Teratogen isotretinoin: used in treating cystic acne- * must order a pregnancy test before
placing a woman on the drug, * patient must be on birth control pills while taking the drug,
newborn effects (3 C's): * craniofacial abnormalities (small ears), micrognathia, cleft palate), *
cardiac defects, CNS malformations (hydrocephalus,rnicrocephaly)
Teratogen phenytoin: nail hypoplasia, CNS abnormalities, cleft liplpalate, congenital heart
Maternal smoking: vasoconstrictive effects of nicotine produce placental ischemia- endothelial
damage increases the risk for thrombosis in placental vessels, low birth weight babies
Mothers with SLE: SLE patients who have anti-Ro (anti-SS-A) IgG antibodies in their serum may
have newborns with complete heart block
Teratogen thalidomide: previously used in the United States to control nausea associated with
pregnancy- currently used in Rx of leprosy, limb abnormalities- * amelia (absent limbs), *
phocomelia (seal-like limbs)
Teratogen valproate: open neural tube defects
Teratogen warfarin: contraindicated in pregnancy: should use heparin, CNS defects, nasal
Congenital infections: TORCH syndrome: Toxoplasmosis, Other (HBV, AIDS, parvovirus,
syphilis, etc.), Rubella, CMV (cytomegalovirus), Herpes, increase in IgM in cord blood, vertical
transmission (mother to fetus): transplacental MC type; blood contamination during delivery (e.g.,
HBV); cervical infection (HSV 2, Chlamydia); breast feeding (HIV, HBV, CMV)
Congenital CMV: MC in-utero viral infection: majority are asymptomatic, primarily
transplacental, clinical: bilateral sensorineural hearing loss MC complication; periventricular
calcification; hepatosplenomegaly; chorioretinitis (may lead to blindness), urine culture is gold
standard: urine cytology reveals large, basophilic intranuclear inclusions ("owl eyes") in renal
tubular cells, Rx: ganciclovir (begin with this); foscamet (if the former is not working)
Congenital rubella: primarily transplacental: highest incidence of congenital anomalies in first 8
weeks; virus interferes with protein synthesis and produces a vasculitis, clinical: sensorineural
deafness MC complication, cataracts, patent ductus arteriosus
Congenital toxoplasmosis: primarily-transplacental, contracted by women after exposure to
cat litter: pregnant women should avoid cleaning cat litter during pregnancy, greater risk of fetal
infection later in pregnancy than earlier in pregnancy, clinical: chorioretinitis MC late
complication (often leads to blindness); calcificationsin basal ganglia, Sabin Feldman dye test
(uses live organisms)- "gold standard" test but is rarely performed
Congenital Herpes type 2: primarily contracted by passing through the birth canal in women
actively shedding the virus: women actively shedding the HSV-2 virus are delivered by C-section;
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
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

overall effect-, lyrnphopenia (first change)+ thrombocytopenia-, bone marrow hypoplasia);

vessel changes- thrombosis (early), fibrosis (late, ischemia); skin changes including erythema-,
edema-, blistering-, chronic radiodermatitis-, potential for squamous cell carcinoma; GI tract
with diarrhea
Ultraviolet tight (non-ionizing radiation): UVA: Wood's lamp (black light); UVB: sunburn,
corneal burns from skiing, mutagenic effect on skin (thymidine dimers), UVC: germicidal,
WB-related cancers: basal cell carcinoma is MC skin cancer; squamous carcinoma (precursor is
actinic/solar keratosis); malignant melanoma
Laser radiation: intense localized heat that is equivalent to a third degree bum
Microwave radiation: produces a skin burn, adversely affect pacemaker devices,
inconclusive complications: cataracts, cancer, sterility
Infrared radiation: burns, cataracts
High altitude injury: general: O2 concentration is 21% (normal); decreased barometric
pressure (e.g., only 200 rnm Hg on top of Mt. Everest); hypementilation is essential at high
altitude since it lowers alveolar C 0 2 (respiratory alkalosis) + automatically increases alveolar
PA02-, increases arterial P02, acute mountain sickness: occurs within the first 24-36 hrs of an
ascent above 8000-10,000 feet; headache, lethargy, insomnia, dyspnea; Rx with descent, increase
fluid intake (increased insensible water loss from mucous membrane evaporation), and oxygen;
prevention by acclimatizing before ascending and using acetazolamide, which is a carbonic
anhydrase inhibitor that produces metabolic acidosis-, compensation for the expected respiratory
alkalosis, high altitude pulmonary edema: noncardiogenic
Sites of alcohol (ethyl alcohol, ethanol) reabsorption: small intestine- 75%, stomach- * 25%,
* partially metabolized by alcohol dehydrogenase
Liver metabolism of alcohol:
alcohol dehydrogenase aldehyde dehydrogenase (blocked by disulfuam)
alcohol +
- acetaldehyde + NADH - b acetate + NADH + acetyl CoA
Pharmacologic action of alcohol: CNS depressant in descending order-, cerebral cortex-,
limbic system-, cerebellum-, lower brain stem, potentiates inhibitory neurotransmitters like y-
arninobenzoic acid, aldehyde dehydrogenase deficiency: affects -40% of Asians; build-up of
acetaldehyde and GI upset (similar to action of disulfiram), alcohol toxicity: 50 mg/dL euphoria,
gregarious; 100 mg/dL legally drunk in most states (slurred speech, uncoordinated); 300-350
mg/dL stupor or coma; >500 mg/dL death, delirium tremens: following occur 3-5 days after
complete withdrawal-, tremulousness, disorientation, visual hallucinations, agitation; Rx with IV
diazepam and thiamine
Diseases where alcohol is the leading cause: thiamine deficiency: Wernicke's syndrome,
Korsakoff's psychosis, congestive cardiomyopathy, macrocytic anemia: folate deficiency,
acquired sideroblastic anemia- rnicrocytic anemia with ringed sideroblasts, Mallory Weiss
syndrome: tear of the distal esophagus/proximal stomach from retching, Boerhaave's
syndrome: rupture of the distal esophagus/proximal stomach from retching, cirrhosis,
esophageal varices: effect of portal vein hypertension due to alcoholic cirrhosis, fatty change in
the liver, hemosiderosis: alcohol increases the reabsorption of iron, acute and chronic
pancreatitis, type IV hyperlipidemia: alcohol increases synthesis of VLDL, Klebsiella
pneumoniae pneumonia
Alcohol as a cancer risk: squamous carcinoma (synergistic with smoking): oropharynx, mid-
esophagus, larynx, * adenocarcinoma: pancreas, liver
Alcohol effects on CNSIPNS: Wernicke's syndromeKorsakoffs psychosis, cerebellar
degeneration: Hu and Yo antibodies noted in spinal fluid, dementia, DTs, distal peripheral
Note: This material is copyrighted. All rights resewed. Edward Goljan, M.D. 2003

neuropathy, central pontine myelinolysis: demyelination syndrome due to rapid IV Rx of

Smoking epidemiology: MCC of premature death in the United States, MC single
preventable cause of cancer, incidence of smoking is increasing in women and decreasing in
men, nicotine intake can be monitored by measuring plasma or urine level of cotinine: cotinine is
only derived from the metabolism of nicotine, MOA of nicotine: absorbed rapidly into the
pulmonary circulation; moves into the brain where it attaches to nicotinic cholinergic receptors to
produce its gratifying effects/complication of smoking; highly addictive agent, inactivation of
the p-53 suppressor gene by a point mutation on chromosome 17 is the MC genetic defect in
smoking-induced cancer
Cancers where smoking is the leading cause: lung cancer: squamous, small cell, and
adenocarcinoma to a lesser extent, MCC of death due to cancer in both men and women,
oral pharyngeal and laryngeal and mid-esophageal squamous cancer, pancreatic adenocarcinoma,
transitional cell carcinoma of bladder, renal adenocarcinoma,
Smoking effects on the cardiovascular/CNS systems: increases risk for AMI: increased risk for
recurrent AM1 as well, increases risk for sudden cardiac death, increases risk for peripheral
vascular disease, increases risk for strokes, contributing factors: enhanced atherosclerosis due to
chemicals in smoke and nicotine effect on blood pressure and heart rate; atherogenic lipid profile;
tissue hypoxia secondary to excess carbon monoxide (CO); hypercoagulability
Smoking effects on the respiratory system: COPD; -80% of all cases, chronic bronchitis,
emphysema, recurrent infections: pneumonia, URIs, exacerbates bronchial asthma, cancer
Smoking effects on the GI system: GERD, delays the rate of ulcer healing, increased risk for
oral, upper and lower GI cancer
Effects of smokeless tobacco (snuff, chewing tobacco): nicotine addiction, oral
leukoplakialcancer: inside the lip, under the tongue or cheek, verrucous squamous cancer,
nasal cancer- snuff users, aggravation of cardiovascular disease: nicotine effect
Smoking effects on bone and menopause: increases the risk for osteoporosis in men and
women, biochemical reaction in women: estradiol (most potent estrogen) is normally metabolized
in the liver into estrone, which is metabolized into methoxyestrone (no hormonal activity) or estriol
(strong estrogen activity)+ smokers have greater conversion of estrone into the inactive metabolite
leading to low estriol levels-, low levels of estrogen increase the risk for osteoporosis and
premature menopause
Passive smoking effect on children: pathogenesis of passive smoke effects: 75% of total
combustion product in a cigarette is exhaled; risk of passive smoke extends to children as well as
adults, increases the incidence of SIDS, increases risk for lung cancer: 1-2 times increased
cancer risk, exacerbates asthma, increases risk for otitis media, increases risk for recurrent
upper and lower respiratory infections
Miscellaneous smoking effects: increases risk for developing proteinuria in diabetes mellitus,
directly responsible for -25% of residential fires, vitamin C deficiency
Beneficial effects smoking cessation: longevity: smokers who quit before 50 yrs of age have half
the risk of dying over the next 15 yrs than a smoker has, lung cancer: in 10 yrs, there is a 50%
reduction in lung cancer when compared to a smoker, afier 15 yrs, there is only a 16% risk for lung
cancer when compared to a smoker, AMI: AM1 risk approaches that of a nonsmoker after 1 yr of
abstinence, pregnancy: pregnant women who stop smoking in the first trimester reduce the risk of
a low birthweight baby to that of a nonsmoker, forced expiratory volume in 1 second (FEV,,): it
is not improved by cessation of smoking; rate of decline is similar to that of a non-smoker
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

Drugs and interstitial pulmonary fibrosis: amiodarone, bleomycin, busulfan,

cyclophosphamide, nitrofurantoin, nitrosourea, methysergide- also retroperitoneal fibrosis and
Raynaud phenomenon, methotrexate, procarbazine
Ockupation exposure relationships: automobile mechanic: carbon monoxide, pesticide
industry: organophosphates; arsenic, meat packing: polyvinyl chloride with risk of hepatic
angiosarcoma, insulatioddemolitiodroofing material: asbestos: lung cancer, mesothelioma,
fibrous pleural plaques (MC overall complication of asbestos); formaldehyde, dry
cleaning: carbon tetrachloride with liver necrosis due to free radicals, rubberlchemical industry:
benzene: aplastic anemia, leukemia; aniline dyes: bladder cancer, battery, smelter,
p1umberlfoundry:lead poisoning; painter: methylene chloride (converted into carbon monoxide),
solvents, lead, petroleum: benzene, polycyclic hydrocarbons: lung cancer, sewer worker:
hydrogen sulfide gas (sulfhemoglobinemia)
Isopropyl alcohol (rubbing alcohol) poisoning: metabolism: metabolic end-product in the
liver is acetone: no metabolic acidosis unlike other alcohols; increases serum osmolal gap:
difference between calculated and measured serum osmolality >lo, clinica1:deep coma with
Methyl alcohol (Wood's alcohol): increased anion gap metabolic acidosis (converted into
formic acid), optic neuritis and potential for blindness, Rx with IV ethanol: ethanol is a
competitive antagonist with methyl alcohol for alcohol dehydrogenase
Ethylene glycol (antifreeze): increased anion gap metabolic acidosis (converted into oxalic acid),
renal failure fiom calcium oxalate crystals obstructing the lumens, Rx with IV ethanol: ethanol
is a competitive antagonist with methyl alcohol for alcohol dehydrogenase
Mercury poisoning: MOA: toxic in inorganic (elemental) form: dental amalgams, used to be
used in hat making industry ("mad hatter disease"); toxic in organic form: fungicides, contaminated
fish, clinical: diarrhea; visible on x-rays; nephrotoxic ATN involving the proximal tubules;
cerebrallcerebellar neuron loss; constricted visual fields, Rx:dimercaprol
Arsenic poisoning: sources: pesticides, animal dips, Fowler's solution; Rx of syphilis in 19301s,
clinical: garlic odor to breath; severe diarrhea: "rice water" stools similar to cholera; arsenic
melanosis: gray skin with dark macules; squamous cell carcinoma of skin and lungs; nails have
transverse bands (Mees nails): concentrates in keratinlhairlnails; convulsionslcoma: MC COD;
nephrotoxic acute tubular necrosis involving proximal tubules; liver angiosarcoma, Rx:
Mushroom poisoning (Amanita): MOA: toxin inhibits RNA polymerase, abdominal
paidvomiting, bloody diarrhea, jaundice: extensive fatty change
Petroleum product (gasoline, kerosene) disorders: euphoria (drunkacting) when inhaled (or
ingested), addicting, toxic doses: convulsions, tinnitus, non-cardiogenic pulmonary edema
Poisonous snake envenomations: types: pit vipers: rattlesnakes (MC bite), water moccasins,
copperheads; true cobras: coral snake (neurotoxin that blocks acetylcholine release-, paralysis
and death, similar to botulinum poison); coral snake has following color banding: "red and yellow
kill a fellow" (red and yellow bands next to each other), harmless scarlet king snake: "red and black
friend of jack" (red and black bands next to each other), pit viper envenomations: local
swelling/necrosis;hematologicproblems: DIC; antivenin is available: danger of serum sickness
Testicles in hernia sac versus hydrocele: testicles are not translucent, translucency in the
scrota1 sac implies a hydrocele
Visual field defect with craniopharyngioma: bitemporal hemianopsia (impinges on optic chiasm)
Patient with normal PT, P I T , bleeds after surgery even after receiving fresh frozen plasma
and packed RBCs: quantitative platelet problem (thrombocytopenia) or qualitative problem
(patient on NSAlDs)
Note: This material is copyrighted. All rights resewed. 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-
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
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
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
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
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
African American took primaquine and then developed an anemia with bite cells: G6PD
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
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
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
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
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
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
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

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

An estimate of BMR is obtained by multiplying the body weight in kilograms (1

kg equals 2.2 lbs) by 24: BMR = 24 x weight in kg
b. Other factors affecting BMR include gender (males higher than females), fever -
(increases BMR), age (children higher than adults), and thyroid function (increased in
hyperthyroidism and decreased in hypothyroidism).
2. Thermic effect of foods accounts for -10% of daily energy expenditure and represents -
the energy used in digestion, absorption, and distribution of nutrients.
3. Physical activity is variable and is expressed as an activity factor, which when
multiplied by the BMR equals the daily energy expenditure.
The activity factor for a sedentary person is 1.3, moderately active person 1.5, and -
very active person (e.g., manual digging, marathon runner) 1.7.
4. Sample calculations: calculate the BMR and daily energy expenditure for a 220 lb man
(patient A) with sedentary habits and a 110 lb woman (patient B), who runs 10 miles a day
and is an aerobic exercise instructor at night.
a. Patient A: 220 lb = 22012.2 = 100 kg. BMR: 24 x 100 = 2400 kcallday. Daily energy
expenditure: 2400 x 1.3 = 3 120 kcallday
b. Patient B: 110 lb = 11012.2 = 50 kg. BMR: 24 x 50 = 1200 kcallday. Daily energy
expenditure: 1200 x 1.7 = 2040 kcallday
Dietary Fuels:
A. Carbohydrates, fats, and protein (lesser extent) are the primary fuels.
B. Carbohydrates have a protein-sparing effect.
1. An adequate intake of carbohydrate provides the glucose that is necessary for complete
oxidation into C02 and H2O via glycolysis and the citric acid cycle.
2. An inadequate intake of carbohydrate (e.g., < 150 glday) causes degradation of skeletal
muscle with the release of amino acids that are deaminated and converted into substrates
(e.g., pyruvate) for gluconeogenesis.
C. Protein energy malnutrition results from inadequate intake of protein andlor calories.
1. Marasmus is caused by a diet deficient in both protein and calories (e.g., total calorie
It is marked by extreme muscle wasting ("broomstick extremities") due to breakdown
of muscle protein for energy, as well as growth retardation.
2. Kwashiorkor is caused by a diet inadequate in protein in the presence of an adequate
caloric intake consisting primarily of carbohydrates.
Note: This material is copyrighted. All rights resewed. Edward Goljan, M.D. 2003

(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
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
(2) Protein kcal: 108 g x 4 kcallg = 432 kcallday; protein percent = 43213600 = 12%
(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%
(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

C. Thiamine (vitamin B1)

1. Thiamine is present in unrefined cereal grains, Brewer's yeast, meats, legumes, and nuts.
2. Thiamine pyrophosphate is the active form of the vitamin.
3. It is a cofactor for dehydrogenases in oxidative decarboxylation of a-keto acids (e.g.,
pyruvate dehydrogenase conversion of pyruvate into acetyl CoA) and for transketolase
(two-carbon transfer reactions) in the pentose phosphate pathway.
4. Thiamine deficiency most commonly occurs in alcoholics or malnourished individuals.
a. The majority of the clinical findings in thiamine deficiency are due to loss of ATP
from dysfunction of the pyruvate and a-ketoglutarate dehydrogenase reactions which
normally gain 2 NADH (6 ATP).
b. Intravenous infusion of a glucose-containing fluid may precipitate acute thiamine
deficiency in alcoholics (used up by pyruvate dehydrogenase reaction) manifested by
the Wernicke-Korsakoff syndrome (see Table).
D. Riboflavin (vitamin B S
1. Riboflavin is present in meats, poultry, fish, and dairy products.
2. FAD and FMN are the active forms of the vitamin.
a. FAD is produced in the citric acid cycle.
b. PMN is a component of the electron transport chain (ETC) and accepts two
hydrogen atoms (becomes FMNH2) from NADH in a reaction catalyzed by NADH
3. Riboflavin deficiency is usually seen in severely malnourished individuals or pure vegans,
who lack intake of dairy products.
E. Niacin (vitamin B, or nicotinic acid)
1. Sources of niacin include meat, lime-treated (releases bound niacin) or fortified cereals,
and tryptophan-containing proteins.
2. The two active forms of niacin are NAD+and NADP+.
a. Excess tryptophan is metabolized to niacin and supplies -10% of the niacin
b. NAD' and NADP' are important cofactors in redox reactions.
NAD' reactions are primarily catabolic (e.g., glycolysis).
NADP' reactions are primarily anabolic (e.g., FA synthesis).
3. Niacin deficiency, known as pellagra, primarily occurs in people who have diets
deficient in both niacin and tryptophan or in conditions where tryptophan is lost in
urine and feces (e.g., Hartnup's disease) or excessively utilized (e.g., carcinoid
a. Corn-based diets are particularly prone to pellagra since maize protein has a low
tryptophan content and niacin is in a bound form that cannot be reabsorbed.
b. Hartnup's disease is an AR disease with a defect in the intestinal and renal
reabsorption of neutral amino acids (e.g., tryptophan).
c. In the carcinoid syndrome, tryptophan is used to synthesize serotonin, which
produces the flushing and diarrhea associated with the syndrome.
d. Clinical findings associated with pellagra: see Table
4. Excessive intake of niacin leads to flushing due to vasodilatation.
F. Pantothenic acid (vitamin BS)
1. It is a component of cofactor A (CoA) and the fatty acid synthase complex, which is
involved in FA synthesis.
2. Pantothenic acid deficiency is uncommon.
G. Pyridoxine (vitamin Ba)
1. It is present in poultry, fish, liver, pork, soy beans, and nuts.
2. Pyridoxal phosphate is the active form of the vitamin.
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
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
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),
Pantothenic acid None described.
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

pernicious anemia), increased plasma homocysteine,

increased urine methylmalonic acid.
Folic acid Same as vitamin BIZdeficiency with the following exceptions:
no neurologic dysfunction and normal urine methylmalonic acid.
Biotin Dermatitis, alopecia, glossitis, lactic acidosis.
Ascorbic acid Bleeding diathesis (ecchyrnoses, hemarthroses, bleeding gums,
(vitamin C) perifollicular hemorrhages), poor wound healing, glossitis.

* 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
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
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
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

c. Important in normal bone and tooth development

d. Supports spermatogenesis and placental development
e. Used in the treatment of skin disorders and acute promyelocytic leukemia
(1) Topical tretinoin (all-trans-retinoic acid) is used in the treatment of psoriasis
and mild acne.
(2) Oral isotretinoin is used to treat severe cystic acne, but it is teratogenic, so
women must have a pregnancy test before it is prescribed.
(3) All-trans-retinoic acid is used to treat acute promyelocytic leukemia (M.3)
and is thought to induce maturation of the leukemic cells.
4. Causes of vitamin A deficiency include a diet poor in yellow and green vegetables and fat
malabsorption (e.g., celiac disease).
5 . Causes of vitamin A excess include eating bear liver (hunters) and isotretinoin therapy.
E. Vitamin D
1. It is present in liver, egg yolk, saltwater fish (cod liver oil), and fortified foods.
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

2. Synthesis of calcitriol(1,25-dihydroxycholecalciferol), the active form of the vitamin,

occurs in the following sequence.
a. Preformed vitamin D in the diet consists of cholecalciferol (vitamin D3) and
ergocalciferol (vitamin D2, found in plants), which is interconvertible with vitamin
b. Endogenous vitamin D is produced by photoconversion of 7-dehydrocholesterol
to vitamin D3in sun-exposed skin (most important source of vitamin D).
c. The first hydroxylation, which produces 25-hydroxycholecalciferol, occurs in the
liver within the cytochrome P450 system.
d. The second hydroxylation, by 1-a-hydroxylase, produces 1,25-dihydroxy-
cholecalciferol (calcitriol) and occurs in the proximal tubules of the kidneys.
The activity of 1-a-hydroxylase in the kidneys is enhanced by parathyroid
hormone (PTH) and low serum phosphorus levels.
e. Receptors for vitamin D are located in the intestine, kidneys, and on osteoblasts in
3. Functions of vitamin D
a. It increases intestinal reabsorption of calcium and phosphorous and renal
reabsorption of calcium.
(1) Reabsorption of calcium and phosphorous provides an adequate solubility
product (calcium x phosphorus) for vitamin D to mineralize bone: the
crystalline salt deposited in bone is called hydroxyapatite- Calo(P04)a(OH)2.
(2) When vitamin D interacts with its receptors on osteoblasts, alkaline phosphatase
is released: it hydrolyzes pyrophosphate, an inhibitor of bone mineralization.
b. Along with PTH, it increases the mobilization of calcium from bone by
stimulating the conversion of macrophage stem cells in the bone marrow into
Along with PTH, calcitriol maintains the serum calcium concentration.
4. Causes of vitamin D deficiency
a. Renal failure (most common cause): due to deficiency of 1-a-hydroxylase enzyme
b. Fat rnalabsorption: cannot reabsorb fat-soluble vitamins (e.g., celiac disease)
c. Chronic liver disease: cannot carry out the first hydroxylation of vitamin D3
d. Enhanced liver cytochrome P450 system (e.g., alcohol, phenytoin, barbiturates):
increased metabolism of 25-hydroxycholecalciferol.
e. Inadequate exposure to sunlight: decreased synthesis of cholecalciferol (D3)
f. Primary hypoparathyroidism: PTH is required for enhancing the activity of l-a-
g. Type I vitamin D-dependent rickets: deficiency of 1-a-hydroxylase
h. Type KI vitamin D-dependent rickets: deficiency of vitamin D receptors in target
5 . Patients taking megadoses of vitamin D may develop vitamin D toxicity.
F. Vitamin E
1. a-Tocopherol has the highest biological activity of the naturally occurring tocopherols that
constitute vitamin E and is abundant in fruits, vegetables, and grains.
2. It is an antioxidant and scavenger of free radicals that protects polyunsaturated fats and
FAs in cell membranes from lipid peroxidation and also protects low density lipoprotein
(LDL) fkom oxidation.
Oxidized LDL is more likely than non-oxidized LDL to cause atherosclerosis.
3. Vitamin E deficiency is uncommon and primarily occurs in children with
malabsorption secondary to cystic fibrosis and in abetalipoproteinemia.
4. Patients taking megadoses of vitamin E may develop vitamin E toxicity.
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

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
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
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

Vitamin Signs and symptoms of deficiency Signs and symptoms of excess

Vitamin A Night blindness (nyctalopia), eye Increased intracranial pres-
abnormalities (dry eyes, blindness), sure (papilledema,
skin abnormalities (follicular convulsions),
hyperkeratosis, dry skin), lung liver toxicity, bone pain.
abnormalities (bronchitis, pneu-monia, ?
lung cancer), growth retardation,
poor wound healing.
Vitamin D Rickets in children and osteomalacia Hypercalcemia, kidney
in adults, findings in both conditions: stones.
path-ologic fractures, excess osteoid,
bowed legs, findings in rickets only:
craniotabes (soft skull), skeletal
deformities, rachitic rosary, defective
epiphyseal plates with growth
Vitamin E Hemolytic anemia, peripheral neuro- Decreased synthesis of
pathy, dorsal column degeneration vitamin K-dependent
(poor joint sensation, absent vibratory coagulation factors (enhances
Note: This material is copyrighted. All rights resewed. Edward Goljan, M.D. 2003

sensation), retinal degeneration, anticoagulation effect of

myopathy. coumarin derivatives).
Vitamin K Bleeding diathesis (gastrointestinal Hemolytic anemia and
bleeding, ecchymoses), prolonged jaundice in newborns if mother
prothrombin time. receives excess vitamin K.

Minerals and electrolytes

A. Minerals (RDA > 100 mg/day) and trace elements (RDA < 100 mglday), along with vitamins,
are micronutrients that are required in the normal diet.
B. Most minerals are found in the body fluids as electrolyte solutions.
C. Calcium
1. Sources of calcium include dairy products, green leafy vegetables, legumes, nuts, and
whole grains.
2. Functions of calcium
a. Bone formation and teeth
b. Nerve conduction
c. Skeletal, cardiac, smooth muscle contraction
d. Binds to vitamin K-dependent coagulation factors and activates factor Xm to cross-
link fibrin strands
e. Calcium-calmodulin complex activates enzymes for signal transmission across
membranes (e.g., adenylate and guanylate cyclase, phosphodiesterase)
3. Regulation of calcium
a. PTH increases reabsorption in the early distal tubule of the kidneys and mobilizes
calcium from bone.
b. Vitamin D (calcitriol) increases calcium reabsorption in the intestine and kidneys
(see above).
c. Calcitonin, which is synthesized by C cells in the thyroid gland, inhibits osteoclasts,
hence inhibiting the release of calcium from bones.
d. Approximately 40% of calcium is bound to albumin, 13% to phosphorus and
citrates, and 47% circulates as free, ionized calcium, which is metabolically
(1) Alkalotic conditions decrease ionized calcium levels by increasing the amount of
calcium bound to albumin: an alkalotic state increases the number of negative
charges on albumin (less hydrogen ions), hence proportionately more calcium is
bound to albumin at the expense of the ionized level.
(2) Hypoalbuminernia decreases the total serum calcium without altering the ionized
I calcium level.
4. Causes of hypocalcemia
a. Hypoalbuminemia: most common non-pathologic cause
b. Hypomagnesemia: most common pathologic cause; see below
c. Vitamin D deficiency: see above
d. Primary hypoparathyroidism
5. Causes of hypercalcemia
a. Primary hyperparathyroidism: most common cause in the ambulatory
b. Malignancy: most common cause in a hospitalized patient
c. Sarcoidosis: granuloma synthesis of vitamin D
D. Phosphorus
1. It is the most abundant intracellular fluid anion.
2. Most foods contain phosphorus.
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

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
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
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
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
(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
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

(2) Hemochromatosis is an AR disease characterized by unrestricted reabsorption

of iron from the duodenum leading to an accumulation of iron in liver, heart,
pancreas, skin, and other tissues.
(3) Either condition can cause cirrhosis of the liver, bronze skin color, diabetes
mellitus, malabsorption, and heart failure.
e. Transferrin, the primary binding-protein for iron, is synthesized in the liver and
transports iron to macrophages in the bone marrow for storage or to the developing
RBCs for Hb synthesis.
(1) When iron stores in the bone marrow macrophages are decreased (e.g., iron
deficiency), liver synthesis of transfemn increases, which increases total iron-
binding capacity.
(2) When iron stores in the bone marrow macrophages are increased (e.g.,
hemochromatosis), transfenin synthesis is decreased, which decreases total iron-
binding capacity.
3. Causes of iron deficiency vary by age.
a. Newborn: bleeding Meckel's diverticulum
b. Child: bleeding Meckel's diverticulum, milk diet
c. Woman < 50-years-old: menorrhagia
d. Man < 50-years-old: peptic ulcer disease
e. Men and women over 50-years-old: colon polyp or cancer
4. Causes of excess serum iron
a. Iron poisoning: common in children; causes hemorrhagic gastritis and liver necrosis
b. Iron overload diseases: hemochromatosis (see above), hemosiderosis (see above),
sideroblastic anemia (due to pyridoxine deficiency, lead poisoning, alcoholism)
Sideroblastic anemias are associated with excess iron accumulation in
mitochondria owing to problems in heme synthesis.
Excess iron in mitochondria produces ringed sideroblasts (mitochondria are
located around the nucleus of immature RBCs).
1. Sources of zinc include meat, liver, eggs, and oysters.
2. Zinc primarily serves as a cofactor for metalloenzymes.
a. Superoxide dismutase
b. Collagenase: important in remodeling of a wound and replacing type III collagen
with type I collagen to increase tensile strength
c. Alcohol dehydrogenase: converts alcohol into acetaldehyde
d. Alkaline phosphatase: important in bone mineralization; marker of obstruction to bile
flow in the liver or common bile duct
3. Zinc is also important in spermatogenesis and growth in children.
4. Causes of zinc deficiency
a. Miscellaneous diseases: alcoholism, rheumatoid arthritis, acute and chronic
inflammatory diseases, chronic diarrhea
b. Acrodermatitis enteropathica: AR disease associated with a dermatitis, diarrhea,
growth retardation in children, decreased spermatogenesis, and poor wound healing
1. Sources of copper include shellfish, organ meats, poultry, cereal h i t s , and dried beans.
2. Copper primarily serves as a cofactor for metalloenzymes.
a. Ferroxidase: binds iron to transferrin; causes iron deficiency if deficient
b. Lysyl oxidase: cross-linking of collagen and elastic tissue
c. Superoxide dismutase: neutralizes superoxide, an Oz free radical
d. Tyrosinase: important in melanin synthesis; deficient in albinism
e. Cytochrome c oxidase: component of ETC
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

3. Ceruloplasmin, a copper-binding plasma protein that is synthesized in the liver, is

involved in copper transport and regulation.
4. Copper deficiency (hypocupremia) is most often due to total parenteral nutrition
5. An excess of free copper (hypercupremia) is present in Wilson's disease, an AR disease -
associated with a defect in secreting copper into bile.
Characteristic findings include chronic liver disease, deposition of free copper into the
eye (Kayser-Fleischer ring) and lenticular nuclei (dementia, movement disorder), low
serum ceruloplasmin, and high free copper levels in blood and urine.
D. Iodine
1. Sources of iodine include iodized table salt and seafood.
2. Iodine is used in the synthesis of thyroid hormones. -
3. Iodine deficiency is primarily due to an inadequate intake of seafood or iodized table
E. Chromium 7-
1. Sources of chromium include wheat germ, liver, and Brewer's yeast.
2. It is a component of glucose tolerance factor, which maintains a normal glucose, and is
also a cofactor of insulin, which facilitates its binding to adipose and muscle.
3. Chromium deficiency primarily occurs in patients receiving TPN.
4. Clinical findings associated with chromium deficiency: see Table
F. Selenium
1. Sources of selenium include seafood and liver. -
2. It is a component of glutathione peroxidase, which converts oxidized glutathione into
reduced glutathione in the pentose phosphate pathway.
Glutathione is a potent antioxidant that neutralizes peroxide and peroxide free .-
3. Selenium deficiency is primarily occurs in patients receiving TPN.
G. Fluoride
1. Sources of fluoride include tea and fluorinated water.
2. It is a structural component of calcium hydroxyapatite in bone and teeth (see above).
3. Deficiency of fluoride is primarily due to inadequate intake of fluoridated water.
4. An excess in fluoride is primarily due to an excess of fluoride in drinking water.
Fluorosis is associated with chalky deposits on the teeth, calcification of ligaments,
and an increased risk for bone fractures.
Iron Microcytic anemia (iron deficiency is the most common
cause), low serum femtin, low serum iron, high total iron
binding capacity (correlates with decreased transfenin
synthesis), Plurnrner-Vinson syndrome (esophageal webs,
glossitis, spoon nails, achlorhydria), excessive fatigue.
Zinc Poor wound healing, dysgeusia (cannot taste), anosmia
(cannot smell), perioral rash, hypogonadism, growth
Copper Microcytic anemia (decreased ferroxidase activity),
dissecting aortic aneurysm (decreased cross-bridging of elastic
tissue), poor wound healing
Iodide Goiter (due to relative or absolute deficiency of thyroid
Chromium Impaired glucose tolerance, peripheral neuropathy.
Selenium Muscle pain and wealmess, cardiomyopathy.
Fluoride Dental caries.
Note: This material is copyrighted. A11 rights reserved. Edward Goljan, M.D. 2003

Locations of biochemical processes in cell: cytosol: glycolysis, pentose phosphate shunt, FA

synthesis, glycogen synthesis, mitochondrial matrix: P-oxidation of FAs, TCA cycle, inner
mitochondrial membrane: oxidative phosphorylation, both cytosol and mitochondria:
gluconeogenesis, urea cycle, heme synthesis
Comparison Chart of the Well Fed State, Fasting State, and Starved State: recall that insulin is
the key hormone of the fed state and glucagon of the fasting state
Well fed state Fasting state Starved state

Glycogenesis Increased None None

Glycogenolysis Decreased: none in Increased: early supply None: glycogen used up
the liver, some in of glucose derived from
muscle liver not muscle
Gluconeogenesis None Increased: primary Decreased: just enough to
source of glucose after supply RBCs
Triacylglycerol synthesis Increased None None
in liverladipose
Lipolysis None Increased Increased
Fate of glycerol Synthesize more Substrate for Substrate for
triacylglycerol in liver gluconeogenesis gluconeogenesis
P-oxidation of fatty acids Increased Markedly increased:
primary fuel for muscle
Muscle catabolism None: increased Increased: supply amino Decreased: conserve
protein synthesis and acids for muscle for important body
uptake of amino acids gluconeogenesis functions
Urea synthesislexcretion Remains constant: Increased: deamination Decreased: less muscle
handles N&' load of amino acids used for breakdown of protein with
from protein gluconeogenesis less amino acids to
degradation in gut by increases urea synthesis degrade
Ketone body synthesis None Increased Markedly increased: by-
product of acetyl CoA
from increased p-
oxidation of fatty acids
Muscle use of glucose for Primary fuel Decreased None: mainly uses fatty
fuel acids
Muscle use of fatty acids None Increased: primary fuel Markedly increased:
for fuel primary fuel
Muscle use of ketones None Some: alternative fuel None: allows the brain to
for fuel use ketones for fuel
Brain use of glucose for Remains constant Remains constant Decreased: allows RBCs
fuel to primarily use glucose
for fuel
Brain use of ketones for None None Increased: primary fuel
RBC use of glucose for Remains constant Remains constant Remains constant
Rate limiting reaction in cholesterol synthesis: HMG Co reductase: inhibited by cholesterol and
statin drugs (competitive inhibition with mevalonic acid), enzyme converts HMG CoA into
mevalonic acid
Note: This material is copyrighted. All rights reserved. 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

competitive inhibitor is reversed by increasing substrate, o methotrexate is also a competitive

Reversible noncompetitive inhibitors: V, is decreased, however the K, remains the same,
reversible noncompetitive inhibitors bind reversibly (noncovalent bonds) away fiom the active
binding site of the enzyme and form either unreactive enzyme-inhibitor complexes or enzyme-
substrate-inhibitor complexes, affinity of the enzyme for substrate is unchanged (K,,,), since the
active binding site is unaltered and normally binds with substrate, V,, is decreased since the
inhibitor inactivates the enzyme, which automatically decreases the effective concentration of
active enzyme, increasing substrate concentration does not reverse the effect of the inhibitor,
since the inhibitor is blocking enzyme activity away from the active binding site, examples of
reversible noncompetitive inhibitors include angiotensin converting enzyme inhibitors (substrate
is angiotensin I); physostigmine, which is a cholinesterase inhibitor (substrate acetylcholine); and,
allopurinol, an xanthine oxidase inhibitor (substrate xanthine), irreversible inhibitors
permanently inactivate enzymes by forming strong covalent bonds: examples include lead
(irreversibly inhibits ferrochelatase and 6aminolevulinic acid dehydrase), aspirin (irreversibly
inhibits platelet cyclooxygenase), and organophosphates (irreversibly inhibit cholinesterase),
enzyme kinetics are the same as those for reversible noncompetitive inhibitors
Urea cycle: r method of eliminating ammonia, located in the hepatocyte, chronic liver disease:
low BUN, elevated ammonia
Cholesterol synthesis: first few steps are similar to ketone body synthesis except HMG CoA lyase
is used instead of HMG CoA reductase
Apolipoprotein 100 (liver) and 48 (intestine)
Liver can not use ketones for fuel: liver cannot activate acetoacetate in the mitochondria, which
requires succinyl CoA: acetoacetate CoA transferase (a thiotransferase enzyme) in order to convert
AcAc into acetoacetyl CoA.
Insulin: key hormone of the fed state, activates phosphatase (dephosphorylation)
Glucagon: key hormone of the fasting state, activates protein kinase (phosphorylation)
Major source of NADPH: pentose phosphate shunt, malate dehydrogenase (malic enzyme)
reaction to a lesser extent, NADPH supplies reducing equivalents
Mechanism of ketoacidosis in DKA: increased P-oxidation of fatty acids and production of acetyl
CoA, which is used by the liver to synthesize ketone bodies
Energy in cardiac muscle: P-oxidation of fatty acids
Lipid facts: functions of HDL: reservoir for apolipoproteins in the blood; transport of esterified
cholesterol to the liver; transfers cholesterol esters to VLDL in exchange for triglyceride using
cholesterol ester transport protein; taken up by scavenger receptors in the liver, in patients with
diabetic ketoacidosis you would expect.. . activation of hormone sensitive lipase in the adipose,
conversion of glycerol 3-phosphate into dihydroxyacetone phosphate, in the fasting state, you
would expect: loss of inhibition of carnitine acyltransferase by malonyl-CoA, in the fed state, you
would expect: activation of citrate lyase in the cytosol;inactivation of hormone sensitive lipase in
adipose; increased production of palmitic acid in the cytosol
Findings in PKU: AR disease with deficiency of phenylalanine hydroxylase, newborn must
be exposed to phenylalanine (PHY) in the diet before it is increased, mousy odor, projectile
vomiting simulating congenital pyloric stenosis, tyrosine missing, hence it must be supplied in
the diet, can diagnose by amniocentesis and finding the abnormal gene, eliminate phenylalanine
fiom diet: Nutrasweet is aspartate and phenylalanine, so cannot use it, woman with PKU who
is pregnant must be on a PHY free diet: affected fetus will develop permanent CNS damage
owing to exposure of PHY
Disorders of galactose metabolism: galactose derives fiom lactose metabolism: lactose +
lactase-, glucose + galactose, galactose metabolism in sequence is as follows: galactose +
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

galactokinase + galactose l-PO4, * galactose 1-PO4 + GALT (galactose-1-phosphate uridyl

transferase) + UDP-glucose+ glucose l-PO4 + UDP-galactose, * glucose 1-PO4 +
phosphoglucomutase + glucose 6-PO4 (6 carbon intermediate) * glucose 6-PO4 + glucose 6-
phosphatase (gluconeogenic enzyme)+ glucose, galactokinase deficiency: benign AR disease;
positive urine Clinitest: Clinitest detects all reducing sugars except sucrose, which is not a reducing
sugar, galactosemia: AR disease with deficiency of GALT; excess galactose is converted into the
galactitol (polyol or alcohol sugar), which, like sorbitol, is osmotically active: damages lens, nerve
tissue, CNS, liver; excess galactose 1-PO4 is toxic: cirrhosis, mental retardation, renal damage,
neonatal hypoglycemia (lack of glucose 6-PO4, a substrate for gluconeogenesis); Rx is a lactose
free diet for the first two yrs; pregnant women with galactosemia can synthesize lactose in
their breast milk via the following reactions: UDP-glucose + UDP-hexose epimerase + UDP-
galactose, UDP-galactose + lactose synthetase- lactose + UDP
Disorders in fructose metabolism: fructose metabolism in sequence: sucrose- + sucrase -,
glucose + fructose; fructose + fructokinase + fructose 1-PO4; fructose I-PO4 + aldolase B +
glyceraldehyde 3- phosphate + dihydroqacetone phosphate @HAP, both are 3 carbon
intermediates that are gluconeogenic substrates), hctose can be synthesized from mannose
(and vice versa) and sorbitol, fructose is an essential nutrient for sperm stored in the seminal
vesicles, essential fructosuria: AR disease with missing fructokinase; positive urine Clinitest due
to fructose, hereditary fructose intolerance: AR disease with a deficiency of aldolase B;
accumulation of fructose 1-PO4,which is toxic to the liver (cirrhosis); fasting hypoglycemia due to
a decrease in 3 carbon intermediates for gluconeogenesis; severe hypophosphatemia: excess
fructose traps phosphate in cells, depletion of ATP leads to RBC hemolysis and rhabdomyolysis,
increased adenosine monophosphate (AMP), which is a purine, is converted into uric acid leading
to gout; must eliminate table sugar (sucrose) from the diet
Sorbitol: osmotically active solute that is synthesized in those tissue containing aldose reductase,
which include: lens, seminal vesicles (note in the biochemical reaction listed below how glucose is
converted into fructose in the seminal vesicles), Schwann cells, retina, kidneys, aldose reductase
converts glucose into sorbitol and sorbitol dehydrogenase converts sorbitol into fructose:
N A D ~ A D P N' ~ X D H ~
Glucose Sorbitol Fructose
aldose reductase sorbitol dehydrogenase
hyperglycemic states, like diabetes mellitus, there is an excess of sorbitol produced in the above
tissues leading to osmotic damage: cataracts, peripheral neuropathy due to destruction of Schwann
cells, microaneurysms in retinal vessels due to destruction of pericytes
Homocystinuria: AR disease with a deficiency of cystathionine synthase, metabolism of
homocystine in sequence is as follows: methionine + ATP + S-adenosylmethionine (SAM) +
methyl acceptors + methyltransferme + S-adenosylhomocysteine + methylated products'(donates
methyl groups for 1 carbon transfers); S-adenosylhomocysteine + H20 + homocysteine +
adenosine; homocysteine + serine + cystathionine synthase + cystathionine, in homocystinuria,
both homocysteine and methionine are increased in serum, S/S of homocystinuria that
resemble Marfan syndrome (example of genetic heterogeneity): dislocated lens, arachnodactyly,
eunuchoid, distinctive features of homocystinuria: increase in plasma homocysteine levels leads
to vessel damage/thrombosis (strokes, AMI), mental retardation, increased urine homocysteine
and increased serum/urine methionine
Alcaptonuria and hereditary tyrosinosis: metabolism of phenylalanine is as follows:
phenylalanine + phenylalanine hydroxylase (deficient in PKU)+ tyrosine; tyrosine + 4-
hydroxyphenyl pyruvate + homogentisate; homogentisate + homogentisate oxidase (deficient in
alkaptonuria) + maleylacetoacetate; maleylacetoacetate + fumarylacetoacetate hydrolase
(deficient in hereditary tyrosinemia) + fumarylacetoacetate; fumarylacetoacetate -,acetoacetate +
Note: This material is copyrighted. All rights reserved. Edwar Goljan, M.D. 2003

fbmarate (present in TCA cycle), alkaptonuria: disease with an absence of homogentisate

oxidase; accumulation of black, homogentisate ent in jointslcartilage leads to degenerative
joint disease; urine turns black when oxidized osure to light, hereditary tyrosinosis:
AR disease with a deficiency of fumarylace hydrolase; increase in serum tyrosine:
cabbage-like odor, cirrhosis with an extremely ence of hepatocellular carcinoma, renal
disease (aminoaciduria), death in the first yr of life
w Lysosomal storage diseases: definition: abs
hydrolytic enzymes; accumulation of complex n lysosome: sphingolipids, glycos-
aminoglycans, glycogen (Pompe's disease), m AR diseases with the exception of two
diseases, which are SXR: Fabry's disease, Hun
w Glycosaminoglycans (GAGS) and their
branched, strongly negatively charged polysa th repeating units of amino sugars
0-glucosamine or D-galactosamine) and nic acid or D-glucuronic acid),
chondroitin sulfate: most abundant GAG, t in cartilage, heparan sulfate:

anticoagulant, keratan sulfate, hyal .
mainly responsible for the negative charg

lubricant), dermatan sulfate: ground s

asement membrane, heparin-
onent of synovial fluid (joint
at is increased in valve
prolapse, increased in pretibial myxed disease with a deficiency of
a-1-iduronidase; accumulation of d e mental retardation; coarse
facial features; corneal clouding; co lates in coronary vessels;
vacuoles in peripheral blood leukoc e with a deficiency of L-
iduronosulfate sulfatase; accumul er disease than Hurler's
Sphingolipids and their disor omyelin, cerebrosides,
gangliosides, sphingomyelin: ranes in nerve tissue;
sphingosine is the backbone o produce ceramides:
sphingosine + fatty acids -+ ceramid rylcholine* sphingomyelin,
ceramide + glucose or galactose* gluc ceramide + oligosaccharides +
gangliosides, Tay-Sachs disease: osaminidase (a-subunit): a 4
nucleotide insertion leads to a abnormal hexosaminidase;
accumulation of GMI ganglioside;
retardation by 6 months; blindne e macula; no hepato-
splenomegaly; electron microscopy exhibits who figurations in lysosomes that look exactly
the same as lamellar bodies with surfactant in ocytes, Niemann-Pick: AR disease
with a deficiency of sphingomyelinase; acc hingomyelin: bubbly appearance in
macrophages1 neurons; mental retardation; aly; EM exhibits zebra bodies in
lysosomes: look like zebra stripes, G AR disease with deficiency of
glucocerebrosidase; accumulation of glu brillary appearance (crumbled up
newspaper) in macrophages; adult type as ssive hepatosplenomegaly and an
increase in serum total acid phosphat macrophages, metachromatic
leukodystrophy: AR disease with a defici e A and accumulation of sulfatide:
results in the synthesis of abnormal myel ositive with metachromatic stains;
peripheral neuropathy; urine arylsulfata dfabsent, Krabbe disease: AR
disease with a deficiency of galactosyl mulation of galactocerebroside:
results in the synthesis of an abnormal my motor retardation; multinucleated
globoid cells (histiocytes) in CNS, isease with a deficiency of a-
galactocerebrosidase A and accumulati side; angiokeratomas on skin;
hypertension; renal failure
Glycogen synthesis (glycogenesis) occurs in the fed state) in
sequence: glucose + glucokinase + utase + GI -Po4; GI-PO4
Note: This material is copyrighted. All rights reserved. Edward Goljan, MD. 2003

+ UDP- glucose pyrophosphorylase+ UDP-glucose + UTP + PPi: UDP-glucose + glycogen

synthetase (insulin enhanced, rate limiting enzyme)+ glycogen: branched chain polysaccharide -
of D-glucose residues with a-1-4 linkages, glycogen synthetase produces a-1,4 linkages between
the glucose residues by adding linkages to an already existing glycogen primer, glucosyl 4:6
transferase makes branches by transfemng 5-8 glucosyl residues fiom the non-reducing end of the -

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

Glycogenoses with fasting hypoglycemia: von Gierke's, deficiency of liver debrancher

enzymes, deficiency of liver phosphorylase
c+- Types of mutations:
1. point mutation of a single nucleotide base within a protein-coding gene may have 3
potential outcomes-
A. silent mutation: altered codon specifies the same amino acid without altering the
phenotypic effect- e.g., UUG (lysine) + CUG flysine)
B. rnissense mutation: altered codon specifies a different amino acid leading to variable
phenotypic effects- e.g., UUG (lysine) + UCG (serine)
sickle cell diseaseltrait: point mutation occurs where adenine replaces
thymidine causing valine to replace glutamic acid in the 6th position of the
P-globin chain
normal p chain DNA CTC sickle DNA fkchain CAC
111 A replaces T
Glu Val
C. nonsense mutation: altered codon is a stop codon (UAA, UAG, UGA) causing
premature termination during protein synthesis- e.g., UUG (lysine) + UAG (stop
pthalassemia major: a point mutation produces a stop codon leading to
termination of DNA transcription of P-globin chain
frameshift mutation-
A. caused by insertion or deletion of any number of nucleotides not divisible by 3
B. shifts the reading frame during translation of mRNA leading to a randomly
incorrect amino acid sequence and production of a truncated protein due to
introduction of a premature stop codon
Ala Lys Ser Tyr Leu Ala

delete A
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
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
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
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
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 .

Sex-linked lymphoproliferative syndrome: SXR, B cell deficiency: EBV-related disease, a

hypogammaglobulinemia, a malignant lymphoproliferative disorders
DiGeorge syndrome (thymic hypoplasia): pure T cell deficiency: no inheritance pattern, a
failure of the 3rd (inferior parathyroids/thymus)/4th (superior parathyroids) pharyngeal
pouches to develop, clinical: abnormal facies; hypoparathyroidism with hypocalcernia and
tetany; absent thymic shadow; truncus arteriosus (cyanotic congenital heart disease); chronic
candidiasis; Pneumocystis carinii pneumonia (PCP); graft vs host reaction (must irradiate blood to
destroy donor irnrnunocompetent lymphocytes), Rx: thymic grafts, bone marrow transplants
* Ataxia telangiectasia: AR disease, B/T immunodeficiency: develops in 2-5-year-olds, a
clinical: cerebellar ataxia, telangiectasias in eyesiskin, sinopulmonary infections, chromosome
instability syndrome: increased susceptibility for chromosomal mutations; DNA enzyme repair
defects (increased risk for lymphomaslleukemias), thymic hypoplasia, low IgA/IgE, a increased
serum a-fetoprotein
Hyperacute rejection of a transplant: ABO incompatibility or patient had anti-HLA antibodies
against an HLA antigen in the graft, type I1 hypersensitivity reaction
* HLA-A, B, C code for class I antigens: CD8cytotoxic T cells recognize these antigens
BLA-D loci code for class 11antigens: CD4helper T cells, macrophages recognize
Renal transplantation:
1. sources for a living-donor-
A. siblings: 25% chance for 2-haplotype match, 50% chance for 1-haplotype match, 25%
chance for 0-haplotype match
B. parents are automatically 1-haplotype matches
2. types of renal transplant-
A. cadaver: MC type
B. livingdonor: 1 yr graft survival rate is 90%
3. types of renal disease requiring transplantation in descending order-
A. diabetic nephropathy with CRF
B. hypertensive renal disease
C. chronic glomerulonephritis
4. immunosuppressants used in renal transplant patients-
A. cyclosporine: inhibits IL-2 release from CD4 T helper cells (dose-related
nephrotoxicity: MC effect)
B. azathioprine: inhibits proliferation of activated T cells
C. prednisone: blocks IL-1 and cytokine production from T cells
D. OKT3: monoclonal antibody against T cell antigen receptor
5. hyperacute rejection-
A. type 11 hypersensitivity reaction with vessel thrombosis developing within hours of
transplant surgery
B. anti-HLA antibodies in the recipient that attack donor HLA antigens or ABO
C. irreversible
6. acute rejection-
A. acute rejections occur after the first week or after a few years
B. pathogenesis:
(1) primarily type IV cell-mediated immunity: lymphocyte infiltrate in the
(2) humoral component: vessel thrombosis/fibrosis
C. only rejection that is reversible with Rx
7. chronic rejection:
A. MC type of rejection
Note: 'This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

B. leads to total renal failure in months to years

C. graft exhibits interstitial fibrosis and vessel fibrosis (ischemia)
D. no specific Rx:irreversible
8. tests to evaluate renal transplant rejection- renal biopsy and renal scans
9. causes of death in renal transplant patients- opportunistic infections MCC of death
(CMV, Aspergillus)
Receptor for EBV: CD2, on B cells, polyclonal stimulator causing increased synthesis of
immunoglobulins- reason for hypergammaglobulinemia in AIDS, increased cell divisions
increases risk for t;8:14 and development of Burkitt's lymphoma
M. tuberculosis: mycolic acid in cell wall is responsible for acid-fastness
Antigen that binds to CD4 on T cells in HIV: gp120
Fever in malaria: coincides with rupture of RBCs
Single most important infectious cause of death in the world: tuberculosis
Asthma, massive hemoptysis and external otitis: Aspergillus fumigatus: narrow angle, septate,
Mycobacterium tuberculosis and sarcoidosis are BOTH associated with: granulomatous
hepatitis, the former the MC infectious cause and the latter the MC non-infectious cause
Greenish discoloration of the sputum in a febrile 4-year-old c h i d with cystic fibrosis is MOST
LIKELY due to: Pseudomonas aeruginosa- pyocyanin
Pathogens that are branched with a standard Gram stain: Nocardia asteroides: partially acid-
fast, strict aerobe, Actinomyces: strict anaerobe, sulfur granules, draining sinus tracts in jaw,
thorax, or abdomen
Hiker recently returned from a week long camping trip in Southern Arizona presents with
fever, flu-like symptoms, a non-productive cough and painful red nodules on the anterior
aspect of his lower left leg (erythema nodosum). A solitary coin lesion with an egg shell-like
cavity is noted in the upper portion of his left lower lobe on a chest x-ray: coccidioidomycosis
An asymptomatic, afebrile 48-yearsld Black man, who has lived all of his life in Ohio, is
noted to have multiple calcifications throughout both lung fields and in the spleen:
Most common cause of intestinal tuberculosis in the United States: Mycobacterium
tuberculosis- swallow infected sputum and organisms taken up by macrophages in Peyer's patches
Photochromogen that produces pulmonary tuberculosis: Mycobacterium kansasii
Rapidly growing TB associated with infection in immunocompromised hosts and in prosthetic
devises: Mycobacteriumfortuitum
Pathogen that commonly produces lung abscesses, common secondary invader in the lung in
patients with rubeola or influenza, produces tension pneumatocysts leading to tension
pneumothorax in cystic fibrosis patients: Staphylococcus aureus
Pathogen that is contracted when the newborn passes through the birth canal. I t produces a
pneumonia characterized an abrupt onset of tachypnea, wheezing, hyperaeration,
eosinophilia and a conspicuous lack of fever. I t is often associated with a conjunctivitis:
Chlamydia trachomatis
Systemic pathogen that is often associated with the presence of indwelling venouslarterial
catheters and immunodeficiency states. I t produces a pneumonia characterized by diffuse
nodular infiltrates and evidence of vessel invasion: Candida albicans
Childhood pathogen that may produce a pneumonia associated with Warthin-Finkeldey
multinucleated giant cells: rubeola /

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
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
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
Most common cause of bronchopneumonia and lobar pneumonia in the general population:
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
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
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

Inspiratory stridor is commonly associated with what microbial pathogens: parainfluenza

virus infection (croup), acute epiglottitis
Chlamydia trachomatis and the respiratory syncytial virus are BOTH commonly associated
with: interstitial type of pneumonia
Klebsiella pneumoniae: upper lobe cavitation, thick mucous and fat gram negative rods,
association with an alcoholic
In a man who lives in Tennessee, you would expect a calcified solitary coin lesion in the lung
to represent: an old granuloma (histoplasmosis)
A bridge painter in New York city develops a pulmonary infiltrate. Which of the following
pathogens are on your differential list: Hisioplasma capsulata (starlings), C ~ p t o c o c m s
neoformans (pigeons)
26-year-old male, who presented with a sudden onset of 103O F temperature, dyspnea, cough
productive of rusty-colored sputum, and pleuritic chest pain in the right upper lung. A chest
x-ray reveals a right upper lobe consolidation. A gram stain of sputum is pending:
Streptococcus pneumoniae pneumonia, Rx with Penicillin G
Systemic fungus with broad-based buds presents with a skin disorder simulating squamous
carcinoma as well as lung disease: Blastomyces dermatitidis
Systemic fungus that most simulates primary and reactivation T B and has yeast forms
phagocytosed by alveolar macrophages: Hisioplasma capsuiatum
Pulmonary pathogens that are vessel invaders and have the capacity to produce pulmonary
infarctions: Candida albicans, Pseudomonas aeruginosa, Aspergillus fumigatus, Mucor
Patients who are being treated for tuberculosis may develop sideroblastic anemia:
complication of isoniazid, produces pyridoxine deficiency, Ba is necessary in heme synthesis in
the mitochondria of RBCs, leads to a sideroblastic anemia
Streptococcus pneumoniae: MCC of- meningitis in patients > 18-yrs-old, spontaneous
peritonitis in children with ascites, otitis media, sinusitis
Afebrile 22-year-old man and several other members of his family developed severe vomiting
without diarrhea -1-6 hours after eating potato salad a t a picnic. They all recovered
uneventfully 12-24 hours later: S. aureus with preformed toxin
23-year-old man developed explosive, watery diarrhea with blood, leukocytes, and mucus -3
days after eating chicken that was improperly cooked. Comma-shaped organisms are noted in
the fecal smear of stool along with RBCs and leukocytes: Campylobacterpylori
Febrile 10-year-old child presents with severe right lower quadrant pain that is interpreted
by the attending physician as acute appendicitis. At laparotomy, the surgeon notes that the
appendix is normal. Mesenteric lymph nodes are markedly enlarged and have focal areas of
microabscess formation on cut section: Yersinia enterocolitica
Afebrile 28-year-old medical student develops vomiting and diarrhea 4 hours after eating
rewarmed fried rice from a Mexican restaurant. Gram positive rods are present in his stool.
He recovers uneventfully in 12 hours: Bacillus cereus- preformed toxin
25-year-old medical student during Spring break in Tijuana, Mexico develops fever,
vomiting, abdominal cramps, and watery diarrhea -14 hours after eating a few tacos
purchased from a street vendor. He recovers uneventfully in 48 hours: enterotoxigenic E. coli-
secretory diarrhea
Afebrile 30-year-old man develops profuse watery diarrhea, with abdominal cramps 4 8
hours after eating a dozen raw oysters at a cafe along the Louisiana coast. He is hypotensive,
volume depleted, and has a hypokalemic normal anion gap metabolic acidosis: Vibrio cholerae
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
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.
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
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
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

production-, second exposure to antigen deposited in tissue leads antigen-antibody ICs-,

complement system activation+ neutrophillmacrophage damage of tissue, examples: serum
sickness: Rx of rattlesnake envenomations with use of horse serum antitoxins; SLE
glomerulonephritis (GN): anti-DNA + DNA ICs; post-streptococcal GN: anti-bacterial antigen
antibodies + bacterial antigen ICs; Henoch-Schgnlein purpura: anti IgA antibodies against IgA;
rheumatoid arthritis: IgM antibodies against IgG (rheumatoid factor), clinical example of an
Arthus reaction: Farmer's lung: antigen is thennophilic actinomycetes
Examples of type N T cell-mediated hypersensitivity reactions: antibody-independentcellular
immune reactions involving CD.4 helper T cells @RH reactions) and CDe cytotoxic T cells, types
of DRH reactions: allergic contact dermatitis: poison ivy, nickel; skin tests: tuberculin sensitivity,
patch test in contact dermatitis; granulomas, pathogenesis of cytotoxic T cell reactions:
cytotoxic T cells normally interact with class I antigens on nucleated cells-, alteration of class I
antigens on target cells activates cytotoxic T cells to release perforins that destroy the cell;
examples: neoplastic/virally infected cell, foreign antigens in a transplant cell
Parasitology terms: definitive host: host that harbors the adult, or sexual stage of the parasite, a
intermediate host: host that harbors the larval, or asexual stage of the parasite protozoa: amebae;
ciliates; flagellates; sporozoa, helminths include: nematodes: roundworms, cestodes: tapeworms,
trematodes: flukes
Scorpions: key words: poisonous species capable of causing fatality lives in Southwestern deserts
(Centruroides gertschi); neurotoxin; bite site shows no initial reaction-, increased sensation-, no
sensation in the area of the bite+ whole extremity becomes numb+ increased blood pressure-,
ascending motor paralysis-, death, Rx: no specific treatment for the poisonous species
Mites: key words for chiggers: pruritic dermatitis best treated with topical antipnuitic agents
(crotamiton and calamine lotion), human itch mite (Sarcoptes scabies): tissue injury by adult
females boring into the stratum corneum; burrows are visible as dark lines between the fingers, at
the wrists, on the nipples, or on the scrotum; females lays eggs at the end of the tunnel: responsible
for intensely pruritic lesion; adults: disease is limited to the webs between the fingers, intertriginous
areas, and spares the soles, palms, face and head; infants: no burrows, and the palms, soles, face
and head are involved; Rx: permethrin cream
Head, body, and the public lice ("crabs"): Pediculus humanis capitis head louse: lays its
"nits," or eggs, on hair shafts; Rx: permethrin (kills newly hatched lice) followed by lindane
(Kwell), if the initial Rx is unsuccessful, Pediculus humanis corporis body louse: lives on the
surface of the skin and breeds in the clothing; Rx the clothing, not the patient: use malathion
powder or DDT powder, Phthiruspubis pubic louse (crabs): lives in the pubic hairs: looks like a
crab; Rx: permethrin
Fire ant bites: sharp, painful bite, wheallflare reaction: type I hypersensitivity reaction, a
reaction followed by vesiculation/skinnecrosis, bites commonly occur in people that crawl under
Interpretation of minimal inhibitory concentration: lowest concentration that drug inhibits
growth, detennine minimal bactericidal concentration: must culture the tubes to see which one has
no growth of the organism
Allopurinol: inhibits xanthine oxidase
Isoniazid: causes pyridoxine deficiency leading to peripheral neuropathy and sideroblastic
anemia, MOA- INH is nicotinic acid derivative that inhibits synthesis of mycolic acid in
mycobacteria cell wall
Effect of aspirin on kidney: decrease PGE2 synthesis (vasodilator) leading to unopposed AT 11
effect, renal papillary necrosis
Methotrexate: blocks dihydrofolate reductase- macrocytic anemia due to folate deficiency, S
phase inhibitor, leucovorin rescue, interstitial fibrosis in lungs
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

Peripheral neuropathy and cancer drug: vincristine

Dapsone: sulfone that inhibits synthesis of folic acid by M. leprae, may precipitate hemolytic
anemia in G6PD deficiency, may produce methemoglobinemia, nephrotic syndrome,
peripheral neuropathy
Heparin: MCC of thrombocytopenia in hospital: type 11hypersensitivity reaction
Acute Rx for coumarin overdose when bleeding is life-threatening: fiesh frozen plasma best
choice, use I M vitamin K for less serious bleeds
Cyclophosphamide: hemorrhagic cystitis, transitional cell carcinoma, activated (not
metabolized) in the liver
Captopril: bradykinin side-effects include cough and angioedema- ACE normally degrades
bradykinin, cough not seen with losartan
Drug used to eliminate calcium in patient with hypercalcemia: loop diuretic
Drug used to remove calcium from urine in a calcium stone former: hydrochlorothiazide
S-phase drug used in treatment of acute lymphoblastic leukemia: methotrexate
ACE inhibitors: block in AT 11 (works as vasoconstrictor of efferent arteriole in glomerulus) by
ACE inhibitor removes important control for maintaining intrarenal blood flow causing potential
for renal failure (particularly with bilateral renal artery stenosis)
Nephron site of action of thiazides: Na+/Cl-pump in cortical thick ascending limb
Vitamin given in Rx of TB: pyridoxine (B6)- used up when using isoniazid, risk of peripheral
neuropathy and sideroblastic anemia
Antihypertensives increasing blood lipids: P-blockers, thiazides
H. pylori: Rx- amoxicillin + clarithromycin + proton pump blocker, prevention- proton pump
blocker + bismuth
HMGCoA reductase inhibitors: statin drugs block CH synthesis, hepatocytes compensate by
up-regulation of LDL receptor synthesis leading to increased clearance of D L and LDL remnants
derived from VLDL
ACE inhibitor effect on plasma renin activity: increases due to decrease in AT 11and aldosterone
Drugs affecting tubulin in mitotic phase: vinca alkaloids, paclitaxel
Use of aqueous epinephrine in shock: 1:1000 dilution subcutaneously
Treatment of acetaminophen overdose: acetylcysteine to replace used up GSH- neutralizes
acetaminophen free radicals formed in the liver cytochrome system
MOA of loop diuretic: blocks N~+-K+-~cI- cotransport pump in the thick ascending limb in the
renal medulla, also blocks calcium reabsorption- used in the Rx of hypercalcemia
Isotretinoin: always order a pregnancy test in females, put patients on BCP
Hair loss in a woman-?drug: oral contraceptives- predictable side effect, estrogen causes hair
to be at same stage of development, may also occur after delivery
Group of drugs has the highest association with urticaria1 and maculopapular lesions:
amoxicillin, TMPISMX, ampicillin/penicillin, rashes are the MC adverse reaction to drugs,
with maculopapular rashes leading the list, most drug reactions involving skin are not type I
hypersensitivity histamine-related, however, those involving penicillin are usually type I
CD4helper T cell count for prophylaxis against PCP: <200 cells/pL- Rx with TMPISMX
CD4 helper T cell count for prophylaxis against toxoplasmosis: <lo0 cells/pL- Rx with
CD4 helper T cell count for prophylaxis against MAX: <50-100 cells/pL- Rx with
Drugs involved in folate metabolism: phenytoin blocks intestinal conjugase- polyglutamate to
monoglutamate, BCP and alcohol block uptake of monoglutamate in the jejunum,
methotrexate~TMP-SMXblock dihydrofolate reductase
Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

Drug induced SLE: procainamide, hydralazine

ACE inhibitors: increase in renin and ATI, but a decrease in ATII and aldosterone, aldosterone
eventually increases, hence the addition of spironolactone to keep aldosterone suppressed-,
increases longevity in CHF
Botulism toxin: blocks the release of acetylcholine- diagram may be given of neurotransmitter
synthesis and must locate the block, used to treat LES spasm in achalasia
A child who ingests 30 adult aspirins will most likely develop?: an increased anion gap
metabolic acidosis, children, unlike adults, do not commonly develop a mixed metabolic acidosis
and respiratory alkalosis, Rx is to perform gastric lavage and add activated charcoal and to
produce an alkaline urine for increased excretion of the acid
Tamoxifen: weak estrogen that acts as an antagonist in breast tissue (estrogen competes with
tamoxifen for binding to the receptor, and partial agonist in uterus (can produce endometrial
hyperplasia), also protects against osteoporosis and can be used in women who have ERA
positive tumors, can be used in treating progestin-resistant endometrial cancer, complications:
flushing (menopausal symptoms), vaginal bleeding, potential for endometrial hyperplasidcancer
Acetaminophen: analgesic and antipyretic but not an anti-inflammatory agent, inhibits
prostaglandin synthesis in the CNS, very weak cyclooxygenase inhibitor, MC drug causing
acute fulminant hepatitis, converted into free radicals in the liver- * glutathione inactivates the
FRs, * acetylcysteine treatment replaces GSH
Drug for bacterial carrier states (S. aureus, N. meningitidis, H. influenzae): rifampin
Single dose drug for GC and Chlamydia: azithromycin
Rx of malignant hypertension: nitroprusside
Estrogen: lipid effects: lowers LDLIVLDL, prevents osteoporosis: inhibits osteoclast
activating factor (DL-1) secreted by osteoblasts, thrombogenic: natural estrogens are less
thrombogenic than synthetic estrogens; increase synthesis of coagulation factors; decrease A m ,
increases liver synthesis of transcortin and thyroid binding globulin: increases total
cortisoVthyroxine levels without an increase in fiee hormone, increases liver synthesis of sex
hormone (testosterone o r androgen) binding globulin- lowers fiee testosterone, cancer risk:
endometrial, breast, intrahepatic cholestasis, cholelithiasis
Oral contraceptives: pill effects: inhibit LH surge, which prevents ovulation, increase malar
eminence pigrnentation:"pregnancy mask", ethinyl estradiol (synthetic estrogen) increases liver
synthesis of many proteins, 19-nortestosterone (progestational agent) effects: water retention/
weight gain; reduction in estrogen receptor synthesis (atrophy of endometrial glands); increase
LDL; decrease HDL, complications: thrombogenic; stimulate tryptophan metabolism: lowers
serotonin-, depression; increases liver synthesis of angiotensinogen: MCC of hypertension in
young women; intrahepatic cholestasis; hepatic adenoma: tendency to rupture; increase
gallstone formation, cancer risks: cervical, breast controversial, hepatocellular carcinoma,
protectivelpreventive effects of pills: fibrocystic change in the breast; endometrial cancer; ovarian
cancer: less ovulation reduces risk for cancer; pelvic inflammatory disease: Neisseria gonorrhoeae
not Chlamydia trachomatis; uterine leiomyomas; endometriosis; acne; rheumatoid arthritis;
Iron toxicity: clinical setting- accidental overdose of ferrous sulfate in children, SIS of iron
Organophosphate poisoning: MOA: irreversible block of acetylcholine esterase
(noncompetitive inhibitor); accumulation of acetylcholine at synapseslmyoneural junctions,
source: pesticides, initial autonomic system overactivity: excessive lacrimation/salivation, fecal
incontinence, constricted pupils, nicotinic effects later in toxicity: muscle weakness/paralysis;
muscle fasciculations, low serum and RBC cholinesterase (pseudocholinesterase), Rx:
atropine Rx of choice; pralidoxime (2-PAM) also may be used
Rx of hypertension (HTN): weight reduction is the most important factor in lowering BP
Note: This material is copyrighted. All rights reserved. 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
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;
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
Electrolyte changes when giving insulin: drives glucose into the cell along with potassium and
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

Respiration changes with increasing altitude: e respiratory alkalosis, hypoxemia due to

decreased atmospheric pressure not a decrease in % oxygen in air, increase in 2,3 BPG right shifts
the ODC
Inhibin: synthesized in Sertoli cells in seminiferous tubules, negative feedback with FSH,
increased if seminiferous tubules are destroyed, normal if Leydig cells are destroyed, since
testosterone has a negative feedback with LH
Calculations: alveolar ventilation- PA02 = Pi02 - PAC02/R, where Pi02 equals % oxygen x
713) and R is the respiratory quotient that normally equals 0.8, subtract Pa02 from PA02 and you
have the A-a gradient, Fick's equation for cardiac output- cardiac output mL1min = oxygen
consumption t oxygen in pulmonary vein - oxygen in pulmonary artery
Placental anatomyiphysiology: maternal surface has slightly bulging areas called cotyledons,
which are covered by a layer of decidua basalis, fetal surface is entirely covered by the chorionic
plate- chorionic vessels converge with the umbilical cord, which is composed of 2 umbilical
arteries (venous blood returning from the fetal heart) and 1 umbilical vein (carries oxygenated
blood from the placenta), chorionic villus/umbilical cord- * chorionic villi project in the
intervillous space, which contains maternal blood from which oxygen is extracted: spiral arteries
from the uterus empty into the space, * chorionic villi are lined by trophoblastic tissue: outside
layer is composed of syncytiotrophoblast: synthesizes hCG and human placental lactogen (growth
hormone of pregnancy) and inside layer is composed of cytotrophoblast: clear cells, the interior of
the chorionic villus has fetal blood vessels, which coalesce to form the chorionic vessels that
converge with the umbilical cord, the umbilical cord contains 2 umbilical arteries (contains
deoxygenated blood exiting the fetal heart and returning to the placenta) and 1 umbilical vein
(contains oxygenated blood)
hCG: has luteinizing hormone activity, keeps corpus luteum of pregnancy synthesizing
progesterone until 8-10 wks and then placenta takes over that function
Atrial natriuretic peptide: mediated by guanylate cyclase, increased if left or right atrium is
volume overloaded
Primary site for temperature regulation: anterior hypothalamus, fever is due to release of
pyrogens stimulating IL-1 release from macrophages: IL-1 increases synthesis of PGE2 in the
anterior hypothalamus; PGE2 raises the hypothalamic set-point (nonnal core temperature viewed as
too low), hence anterior hypothalamic reactions of heat generation prevail, heat generating
mechanisms if core temperature is below set-point include: increasing the release of thyroid
hormones (increases metabolic rate); vasoconstriction of skin vessels (sympathetic stimulation of
a-receptors in smooth muscle); sympathetic stimulation of P-receptors in brown fat (increases
metabolic rate and heat production); shivering (most effective system, center located in posterior
hypothalamus, leads to activation of a and y motoneurons innervating skeletal muscle), heat
dissipating mechanisms (coordinated in posterior hypothalamus) if core temperature is above set-
point include: reducing sympathetic tone (vasodilatation) of skin vessels leading to shunting of
blood through venous plexus in the skin; increased sympathetic activity of cholinergic fibers
innervating sweat glands leading to sweating
Most effective nephron site for acid excretion: proximal tubule of the kidney
Nephron site for ADH effect: collecting tubule
Nephron site for greatest generation of free waterimost susceptible to ischemia: thick
ascending limb in the medulla
Constriction of the efferent arteriole: increases the GFR and decreases renal plasma flow
Collecting tubule
A = Aldosterone
M 2 0= free water: mostly generated in Na+/K+/2~1- cotransport pump
oH20= obligated water; must accompany Na+, Kf, and C1-
ADH = antidiuretic hormone
TAL = thick ascending limb (diluting segment)
DCT = distal convoluted tubule
H* = hydrogen ion that can be secreted with H P 0 i (H2P04), which is titratable acidity or NH3W 4 C 1 )

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

Functional Aspects of the Nephron

Note: This material is copyrighted. All rights reserved. Edward Goljan, M.D. 2003

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
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
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)