ERRATAS AND CLARIFICATION
The new RR Pathology 3rd edition will be out in July or August 2009. It has been
extensively revised with > 2 times more pictures and margin notes; general
treatment for all diseases; and more high yield material has been added to the
tables. It will not only be useful for Step 1 but also your clinical rotations and Step 2.
Page 128
Under B. 3.e.  Increased metabolism of 25-(OH)-D into an inactive metabolite
Page 139
F. 3. Malignant tumors have up-regulation of telomerase activity
Page 149
C. 1. a. Generalized catabolic reaction
Page 150
Table 8-7: add to Eaton-Lambert syndrome: antibody against calcium channel
Page 171
Discussion box on mitral regurgitation: a pansystolic murmur that does not increase with
intensity on deep held inspiration. Also change the Margin Note right next to the box
to Deep inspiration: no increase in intensity for left-sided heart murmurs and
abnormal heart sounds.
Margin note next to box on discussion of tricuspid regurgitation: Deep, held inspiration:
Page 175
Under 4. c. (2): delete and O2
Page 189
In box discussion of Aortic regurgitation last sentence. It does not increase in intensity on
deep inspiration and…
Page 191
Under A. 1. a. (2) change Leishmanial forms to Amastigote forms…
Under A. 2. b. add after the word infiltrate- with myocardial necrosis is highly…
Page 232
Under III. A. 3. b.  Acute myeloblastic leukemia (AML)
Page 238
D. Acute myeloblastic leukemia
Page 257 under A. 1. b
b. Neutralize activated serine protease coagulation factors
 Factors XII, XI, IX, X, thrombin (activated prothrombin)
Page 261
Under E. 2. b. Degrades factors, V, VIII, and fibrinogen
Page 211
Under H. 2. b. (2) …and trap platelets, RBCs, and WBCs.
Page 297
Under 6. a. Epidemiology and pathogenesis
Page 300
Clarification: Chlamydia, Rickettsia, and Mycoplasma are bacteria but were separated out
for discussion purposes. Will be listed under Bacteria in 3rd edition.
Page 326
Under D. 3. b. (3) Trachea deviated to the ipsilateral side if the majority of the lung is
collapsed.
Page 335
Under M. 2. a. (2) (b) Loss of nitric oxide synthase producing (nitric oxide normally
relaxes LES)
Under M. 2. a. (4)  Destruction of ganglion cells by amastigotes
Page 347
Table 17-4 under Giardia
Detected with antigen test of stool
Page 348
Table 17-5 under discussion of celiac disease- Antigliadin, anti-tissue transglutaminase,
anti-endomysial IgG and IgA are the best tests
The pathogenesis of celiac disease has been worked out much better over the last
few years. The most current concepts are included in the 3rd edition, which is
available to you below. Feel free to copy it and include it in your 2nd edition.
11. Celiac disease
a. Epidemiology
(1) Inappropriate immune response to gluten in wheat product
MN: Celiac disease: immune disease directed against gluten
 Also related proteins in rye and barley
(2) Prevalence of 1% in North America
(3) Common in whites; uncommon in blacks and Asians
(4) Occurs at any age
(a) Highest incidence in infancy
 First introduction to gluten products
(b) Third decade
 Frequent association with pregnancy
(c) Seventh decade
(5) Associations
MN: Celiac disease: greatest association with dermatitis herpetiformis
(a) Dermatitis herpetiformis
(b) Autoimmune disease
 Hashimoto’s thyroiditis, primary biliary cirrhosis
(c) Type 1 diabetes mellitus
(d) IgA deficiency
(e) Down syndrome, Turner’s syndrome
b. Pathogenesis
(1) Multiorgan autoimmune disease
(2) Inappropriate T-cell and IgA-mediated response against gluten in
genetically predisposed persons
 Association with HLA DQ2 (95%) and HLA DQ8 (5%)
(3) Timing and dose when gluten introduced in the diet is important.
(4) Tissue transglutaminase (tTG; deamidating enzyme) in the lamina
propria has a pivotal role.
MN: Celiac disease: tTG has pivotal role
(a) Deaminates mucosally absorbed gluten to produce deaminated and
negatively charged gluten peptides
(b) It also enhances the immunostimulatory effect of the deaminated
gluten peptides
(c) These peptides are phagocytosed by antigen processing cells in the
lamina propria
(d) They are presented in complex with HLA DQ2 or DQ8 to glutenspecific CD4 T helper cells
(e) CD4 T cells produce cytokines that release matrix proteases
causing cell death and degradation in the epithelial cells in the villi.
c. Important diagnostic antibodies
(1) Anti-tissue transglutaminase IgA (most important), IgG
(a) Sensitivity and specificity 98%
(b) Excellent screening test
(2) Anti-endomysial IgA
(a) Sensitivity and specificity 100%
(b) Excellent screening test
(3) Anti-gliadin IgA, IgG
MN: Celiac disease: tTG, EMA, gliadin IgA antibodies
(a) Sensitivity 80%, specificity 85%
(b) Moderately good screening test
d. Clinical findings
(1) Steatorrhea
(2) Weight loss
MN: Celiac disease: steatorrhea, weight loss
(3) Failure to thrive in infants and children
(4) Pallor due to anemia (often combined anemias)
(5) Dermatitis herpetiformis
(a) Considered to be a form of celiac disease
(b) Villous atrophy in 75% of cases with or without diarrhea
(c) Low levels of above diagnostic antibodies
(6) Findings related to water soluble and fat soluble vitamin deficiencies
(refer to Chapter 7)
(7) Other systemic findings
(a) Bone osteoporosis, arthritis
(b) CNS seizures, depression
(c) Reproductive delayed puberty, miscarriages, infertility
e. Diagnosis
(1) Above diagnostic antibodies
MN: Celiac disease: flattened villi; hyperplastic glands
(2) Endoscopic biopsy
(a) Flattened villi, particularly in duodenum and jejunum
(b) Hyperplastic glands with intense lymphocytic inflammation
f. Treatment
(1) Gluten-free diet
MN: Celiac disease: gluten free diet
(2) Correct nutritional deficiencies
 All fat soluble vitamins; folate, vitamin B12; calcium
(3) Corticosteroids in refractory cases
Page 357
Table 17-8 under Crohn’s disease; More common in women and replace with No sex
predilection
Page 358
Under M. 1. c. (3) add
(c) Increased risk (> 50%) for colorectal, breast, gynecologic cancers
 This is true even though the GI polyps are hamartomas
Page 365
I. A. 1. b. (2) UCB is conjugated with glucuronic acid to produce conjugated bilirubin
(CB)
Page 367
Table 18-1: Discussion of Crigler-Najar syndromes: add …absent conjugating enzymes
(glucuronyl transferase)
Page 369
Box 18-1: under Normal bilirubin metabolism discussion: …and its conjugation with
glucuronic acid to produce water-soluble conjugated bilirubin (CB+).
Page 384
Box discussion of ceruloplasmin in Wilson’s disease.
Begin the discussion with the following two sentences: Ceruloplasmin is an enzyme that
is synthesized in the liver. It contains 6 atoms of copper in its structure.
The gene defect in Wilson’s disease affects a copper transport system that produces a
dual defect—decreased incorporation of copper into ceruloplasmin in the liver and
decreased excretion of copper into bile.
Page 449
Table 21-1
Chlamydia trachomatis: delete Most common STD
HPV: add Most common STD
Page 458
1. b. (1) Stimulates luteinizing hormone (LH) release
(2) Stimulates follicle stimulating hormone (FSH) release
(a) Positive feedback
(b) Serum LH greater than FSH
Page 461
I. 1. c. (2) Adrenal origin DHEA-sulfate (usually indicates adrenal origin); testosterone
Recall that testosterone is synthesized in the ovaries and adrenal glands. DHT is produced
by peripheral 5--reductase conversion of testosterone to DHT in various sites (skin,
liver, testis, epididymis, seminal vesicles, prostate).
Page 476
E. 1. b. (6) (a) change to Preeclampsia is present in 2% of patients.
Page 504 Table 22-3
Pseudohypoparathyroidism: Autosomal dominant
Clarification: some cases are inherited in an X-linked dominant fashion as originally
stated in the book; however, most are inherited as autosomal dominant
Page 505 Clarification
Hypertension in hypercalcemia:
Hypertension is seen with increased frequency in patients with hypercalcemia (e.g.,
primary hyperparathyroidism). It may be caused by renal insufficiency and/or calciummediated vasoconstriction of arterioles.
Page 506
D. 3. a. Change wording to Glands become autonomous regardless of the calcium level.
Page 507
Table 22-7: under Malignancy-induced hypercalcemia and serum phosphorus levels;
subclassify into lytic and PTHr peptide where former (lytic) will be N for normal, and
the latter (PTHr peptide) will be ; delete the  sign.
Under VII. A. 3. b. Converted to dihydrotestosterone (DHT) by 5-reductase, located in
peripheral tissue
Page 516 (not an errata; just an additional designation)
C. Syndrome X (metabolic syndrome)
Page 528
D. 2. a. Change to RF is an IgM antibody that has specificity against the Fc portion of
IgG.
b. Change to RF immunocomplexes consist of RF complexed with IgG molecules.
Page 580-581
B. 1. b. Pathogenesis: there is a new pathogenesis for multiple sclerosis; below is the new
3rd edition rendering. Feel free to copy it and add it as an insert into your 2nd edition.
a. Pathogenesis
MN: MS: CD4 T cells react against self antigens in myelin sheath; cytokines activate
macrophages that destroy myelin
(1) Autoimmune disease initiated by
(a) Genetic factors (e.g., HLA-DR2)
(b) Environmental triggers
 Microbial pathogens (e.g., Epstein Barr virus, human herpes
virus 6, Chlamydophilia pneumoniae), vitamin D, sun exposure
MN: MS: genetic factors and environmental triggers
(2) Environmental trigger activates helper T-cells whose antigen specific
receptors recognize CNS myelin basic protein (other antigens as well)
as an antigen.
(3) T cells release cytokines that activate macrophages, which also release
cytokines (e.g., tumor necrosis factor-) that destroy the myelin sheath
as well as oligodendrocytes that synthesize myelin
(4) Antibodies directed against the myelin sheath and oligodendrocytes
may also be involved.
Page 582-583
VII. A. Much more is known about the pathogenesis of Alzheimer’s. The most current
rendering is going to used in the 3rd edition is as follows. Feel free to copy this and put it
in your 2nd edition book.
B. Alzheimer’s disease (AD)
1. Epidemiology
MN: AD: most common overall cause of dementia
a. Most common cause of dementia (50-75% of all cases)
(1) Sporadic late onset type of AD (most common)
MN: AD: sporadic late onset type most common type
(2) Sporadic early onset type of AD (before age 65)
 Related to apolipoprotein gene E, allele 4
(3) Familial early onset type of AD (< 1% of cases)
(a) Mutations of amyloid precursor protein (APP) on chromosome 21
(b) Mutations in presenilin 1 on chromosome 14
(c) Mutations in presenilin 2 on chromosome 1
b. Prevalence increases with age.
MN: AD: prevalence increases with age
(1) It is < 1% in the 60-64 year old age group.
(2) It is 40-50% by the age of 95.
c. Trisomy 21 (Down syndrome) has a strong association with AD
 By 40 years of age, most Down syndrome patients have AD
2. Role of -amyloid (A) protein in causing AD
MN: AD:   neurotoxic
a. A is neurotoxic and damages neurons in the following sites
(1) Medial temporal lobe structures
(2) Frontal cortex especially the entorhinal cortex and hippocampus
b. Pivotal role of activated glycogen synthase kinase-3 (GSK) in
neurotoxicity of A
(1) Activation of GSK causes phosphorylation of A, which in turn,
produces
(a) Neuronal and synaptic dysfunction
(b) Signaling for neuronal apoptosis
(2) Phosphorylated A also has a positive feedback on GSK; hence,
keeping the cycle of neurotoxicity in motion
MN: Activated GSK-3: phosphorylates   neurotoxic
(3) Initial activation of GSK has been traced to dysfunction within the
Wnt (Wingless integration pathway), which is a family of genes
normally involved in
(a) Neuronal development during embryogenesis
(b) Normal neuronal function
(4) Normally, the Wnt signaling pathway inactivates GSK; hence,
preventing phosphorylation of A and its harmful effect on neurons
(5) However, if the Wnt signaling pathway is dysfunctional, GSK remains
activated leading to phosphorylation of A and it neurotoxic effects
(e.g., apoptosis of neurons)
MN: 
c. A also deposits in the wall of cerebral vessels.
 Important in producing amyloid angiopathy (see below)
d. A stains positive with Congo red and has apple-green birefringence with
polarization (refer to Chapter 3).
e. A is a metabolic product of amyloid precursor protein (APP)
MN: 
(1) APP is normally coded for on chromosome 21.
(2) Defects in metabolism of APP by secretases cause an increase in A.
(3) -Secretases cleave APP into fragments that cannot produce A.
MN: Secretases: -secretases followed by - secretases cleave APP to produce A
(4) -Secretases followed by -secretases cleave APP into fragments that
are converted to A.
(5) In the sporadic early onset type of AD, apolipoprotein gene E, allele
4 codes for a product that cannot eliminate A
leading to early onset of neurotoxicity.
MN: Insulin degrading enzyme: involved in clearance of A
f. Insulin degrading enzyme
(1) Involved in the clearance of A.
(2) Insulin resistance syndromes (type 2 diabetes; metabolic syndrome)
have increased risk for AD, because increased insulin, lowers insulin
degrading enzyme, which increases A.
MN: Apo gene E, allele 4: codes for product with high affinity for A; sporadic early
onset AD
3. Role of Tau protein in AD
a. Normal function is to maintain microtubules in neurons.
 Assembles and supports scaffolding important in neuron structure and
function
b. Activated GSK enhances hyperphosphorylation of Tau protein
MN: Activated GSK-3: hyperphosphorylates Tau protein
(1) This cause the protein to change shape and cluster into fibers
(2) Fibers appear as neurofibrillary (NF) tangles (twisted fibers) in the
cytoplasm
 Best visualized with silver stains
MN: NF tangle: hyperphosphorylated Tau protein in neuron
(3) NF tangles produce neuronal dysfunction including death of the
neuron.
(4) Pin 1 enzyme (prolyl isomerase) normally strips excess phosphate
molecules from NF restoring it to its original shape; however, in some
cases of AD, this enzyme is absent or dysfunctional.
MN: PIN 1 enzyme: dephosphorylates hyperphosphorylated Tau protein; deficient in
some cases of AD
4. Gross and microscopic findings
a. Cerebral atrophy with dilation of ventricles (hydrocephalus ex vacuo)
(1) Due to loss of neurons in the temporal, frontal, and parietal lobes
(2) Occipital lobe is usually spared.
b. Presence of NF tangles in the cytoplasm of neurons
(1) Best visualized with silver stains
(2) They may occur in other disorders.
• Elderly patients without dementia, Huntington’s disease, NiemannPicks
MN: AD:  density of NF tangles and senile (neuritic) plaques in the brain
c. Senile (neuritic) plaques
(1) Core of A surrounded by neuronal cell processes containing Tau
protein, microglial cells, and astrocytes
 Located in the gray mater.
(2) A stains with Congo red (refer to Chapter 3).
(3) Best visualized with silver stains
(4) Are also normally present in the brains of elderly people
MN: Senile (neuritic) plaques: core of A surrounded by neuronal cell processes with
Tau protein
d. Amyloid angiopathy
(1) A is present in cerebral vessels.
(2) Causes weakening of vessels with increased risk for hemorrhage
MN: Amyloid angiopathy: risk for cerebral hemorrhage
e. Confirmation of Alzheimer’s disease
(1) Requires postmortem examination of the brain
(2) Must be widespread presence of NF tangles and senile plaques
MN: Confirmation of AD: must be made at autopsy
5. Clinical findings
a. Prominent early sign is the decline in short term memory
b. Another early sign is loss of smell
 Dysfunction in entorhinal cortex
c. Patients with mild to moderate disease only have cognitive defects
d. Additional deficits accumulate including changes in behavior, judgement,
language, and abstract thought
MN: AD: prominent early sign is decline in short term memory
e. Even later in the course, functional deficits manifest in the patient not
being able to care for themselves.
f. No focal neurologic deficits are present early in the disease.
g. Patients usually die of an infection.
• Example—intercurrent bronchopneumonia
6. Presumptive diagnosis is made with mental status testing; tests for
MN: AD: presumptive diagnosis with mental status testing; rule out all other causes of
dementia
a. Orientation
b. Attention
c. Verbal recall
d. Language
e. Visual-spatial skills
7. Positron-emission tomography (PET) is useful the differential of dementia
8. Treatment
a. Cholinesterase inhibitors
 Increase synaptic transmission
b. Memantine (blocks NMDA glutamate receptors)
QUESTION 10 (Page 642 has question, page 657 has discussion)
A 9-month-old girl has an infection on her face that began as erythematous macules. She
later develops pustules that rupture and cause honey-colored crusted lesions. The girl's 5year-old brother develops similar lesions. Which of the following is the causal agent?
A.
B.
C.
D.
E.
Staphylococcus aureus
Herpes simplex virus type 1
Malassezia furfur
Propionibacterium acnes
Trichophyton rubrum
A (Staphylococcus aureus) is correct. The child has impetigo, which causes honeycolored crusted lesions that cover shallow ulcerations of the skin. Staphylococcus aureus
is the most common cause of this superficial skin lesion. Streptococcus pyogenes is the
second most common cause of impetigo. Impetigo is highly contagious, which explains
why the child's brother develops similar lesions.
B (herpes simplex virus type 1) is incorrect. Herpes simplex virus type 1 produces
vesicles and pustules on the vermilion border of the lip. It does not produce honeycolored crusted lesions on the face.
C (Malassezia furfur) is incorrect. M. furfur, a superficial dermatophyte, causes tinea
versicolor and seborrheic dermatitis (dandruff). It does not produce honey-colored
crusted lesions on the face.
D (Propionibacterium acnes) is incorrect. P. acnes is an anaerobe involved in producing
the inflammatory reaction associated with acne vulgaris. It does not produce honeycolored crusted lesions on the face.
E (Trichophyton rubrum) is incorrect. T. rubrum, a superficial dermatophyte, causes tinea
corporis (body), tinea cruris (groin), and tinea pedis (foot). It does not produce honeycolored crusted lesions on the face.
QUESTION (I do not know where this question is)
Picture of 1-Antitrypsin deficiency
Which of the following clinical disorders is most compatible with the distribution of
affected patients shown in this pedigree?
A.
B.
C.
D.
E.
1-Antitrypsin deficiency
Hemophilia A
Sickle cell trait
Type 2 diabetes mellitus
Vitamin D–resistant rickets
DISCUSSION OF QUESTION 35
Option A (1-antitrypsin deficiency) is incorrect. 1-Antitrypsin deficiency is an
autosomal dominant (codominant) disorder that involves a defect in either the synthesis
of 1-antitrypsin in the liver or its secretion from the liver. In co-dominant disorders, both
alleles express themselves. The pedigree does not show this inheritance pattern.