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135 Cards in this Set

  • Front
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  • 3rd side (hint)
headaches and visual changes, calcified mass detected on MRI
craniopharyngoma

derivative of rathke's pouch

suprasellar region
cystic spaces lined by stratified squamous epithlium filled with thick yellow-brown, cholesterol rich fluid
craniopharyngoma
headaches and visual changes, calcified mass detected on MRI

derivative of rathke's pouch

suprasellar region
cystic spaces lined by stratified squamous epithlium filled with thick yellow-brown, cholesterol rich fluid
Alpha feto-protein in Adults
>500 indicative of

hepatocellular carcinoma
germ cell tumors
metastatic dz in liver
ataxia telangiectasia
Differentiating Polycythemias
Polycythemia: HCT >48 in woman, >52 in men

Normal RBC Mass: Relative Polycythemia 2° to dehydration/diuresis

True ↑ in RBC mass: absolute polycythemia
--All 3 cell lines increase, low [EPO] = polycythemia vera
--Only RBC's increase: 2° polycythemia
-------Saturation O2 <92% = hypoxia
-------Sat >92% EPO producing tumor
Chediak Higashi Sro
AR sro caused by defect lysosomal trafficking

Results in:

--PMN failure to fuse phagolysosome w/ recurrent pyogenic infx (esp staph & strep)
--albinism
--neurologic abnormalities esp nystagmus & neuropathies
Albino with recurrent pyogenic infections and nystagmus
Chediak Higashi Sro

AR defect lysosomal trafficking

Results in:

--PMN failure to fuse phagolysosome w/ recurrent pyogenic infx (esp staph & strep)
--albinism
--neurologic abnormalities esp nystagmus & neuropathies
How can you prevent infection with an intravenous catheter
the best way to prevent infection is to wash your hands with antibacterial soap prior to catheter insetion
MODY2
glucokinase mutation

glucokinase catalyzes the irreversible conversion of glucose to glucose-6-phosphate, only found in hepatocytes and pancreatic β cells

kinetics: high Km & high Vmax: will not phosphorylate gluocse during fasting conditions, but allows post-prandial trapping in liver

Regulated by Glucokinase Regulatory Protein (GKRP); Fructose-1-phosphate (in equilibrium with glucose-6-phosphate) activates GKRP to bind glucokinase and translocate it to the nucleus where it is non-functional

NB: mutations in glucokinase = MODY2
Neonate with lethargy, vomiting, hypotonia;

Metabolic acidosis with alrge anion gap, ketosis and hypoglycemia

Prioprioc Acidemia
Deficiency of Propionyl CoA carboxylase

Branched Chain Amino Acids (Isoleucine, Valine, Thronine, methionine), Cholesterol and Odd-chain fatty acid catabolism leads to proprionic acid production

propionic acid (ie proprionyl CoA) is converted to Methylmalonyl CoA by Proprionyl CoA carboxylase with a biotin cofactor

Methylmalonyl CoA is isomerized to Succinyl CoA which may enter the TCA cycle
What is the most common cause of aortic rupture?
What is the most common site?
Cause: motor vehicle accidents
site: aortic isthmus, connection between ascending and descending aorta distal to left subclanian artery
What is the differentiating point between direct and indirect hernias
Indirect hernias occur through the deep inguinal ring; Their lateral border is the inferior epigastric vessels ascending off the femoral vasculature. They proceed through the processus vaginalis.

Direct hernias push the transversalis fascia ahead of them. They enter the inguinal ring below the inferior epigastric vessels and continue downwards outside of the spermatic cord.

Indirect hernias are far more common.
Ulcerative mass in the anal canal of AIDS pt
Squamous Cell Carcinoma 2° to HPV
Coronary Sinus Dilation: what is the primary pathology?
Pulmonary Hypertension
thalessemia intermedia
all mRNA begins with the Kozak consensus sequence gccgccRccAUGG
where R is a purine and AUG codes for methionine

point mutation of R to pyrimidine prevents initiation

this is the basis of thalessemia intermedia (β thal)
Type I Glycogenosis
Glucose-6 phosphatase deficiency

Type I Glycogenosis, Von Gierke Dz

Hepatic/renal enlargement
PAS+ glucogen storage vacuoles in many cells

Severe Hypoglycemia: failure to thrive, stunted growth, convulsions
Hyperuricemia (gout)
Xanthomas
Bleeding (platelet dysfnx)
Pompe's Dz
lysosomal α-1,4--glucosidase deficiency
(aka acid maltase);

Type II Glycogen Storage Dz, technically also a lysosomal storage dz

Glycogen in lever, heart, SkM w/ Muscle Hypotonia
Micro: clear glycogen deposits in muscle

Pediatric form: Massive cardiomegaly → early death
Mn: -P-ompe's trashes the -P-ump
Adult form: only SkM involved
McArdle’s Syndrome
aka Type V Glycogenosis

deficiency of muscle phosphorylase produces myopathic glycogenolysis

adult onset: muscle cramps & weakness w/ exercise:

myocytolysis & rhabdomyolysis → ↑ [ammonia]serum, myoglobinuria, abnormal lack of ↑ [lactate]serum

Px: normal longevity

p155; Mn: McArdle-McVardle, the M stands for Muscle
Philadelphia Chromosome
t(9:22)

creates BRC/ABL tyrosine kinase induces CML

Imatinib inhibits BRC/ABL w/o apoptosis
t(9:22)
Philadelphia Chromosome

creates BRC/ABL tyrosine kinase induces CML

Imatinib inhibits BRC/ABL w/o apoptosis
urinary orotic acid excretion
indicative of ornithine transcarbamoylase deficiency

the backup of carbamoyl phosphate is converted to orotic acid

CPS1(CO2 + NH4+ + 2ATP → arbamoyl phosphate) = rate limiting step
the urea cycle

most common disorder?
CPS1(CO2 + NH4+ + 2ATP → arbamoyl phosphate) = rate limiting step

most common dysfnx = OTC (ornithine transcarbamoylase)
→ ↑ NH4+ & ↑ Carbamoyl phosphate → conversion of CP to orotic acid c orotic aciduria
Achalasia
↓ peristalsis & ∅ LES relaxn

Barium Swallow = Bird's Beak Deformity
What are the features of X-linked dominant Inheritance. Describe the features of the X-linked dominant example disease.
Infrequent
Males cannot transmit to sons

Vitamin D resistant Rickets aka X-linked hypophasphatemia: point mutation of vitamin D receptor PHEX → ↑ renal tubular excretn of phosphate → hypophosphatemia → childhood osteomalacia w/ genu varum

[also Rett Syndrome]
Bird's Beak Deformity on Barium Swallow
Achalasia

↓ peristalsis & ∅ LES relaxn
Cori's Dz
Type III Glycogen Storage Dz

debranching enzyme [ α-1,6-glucosidase ] deficiency
accumulation of glycogen in liver, heart, muscle

A milder version of Von Gierke Type I GSDz, as GNG remains intact

Similar Sx: hepatomegaly hypoglycemia: stunted growth, failure to thrive, convulsions
What are the genetic defect and clinical features of Prader-Willi syndrome? Of Angelman syndrome?
Epigeneitc process: selective inactivation of either maternal or paternal allele

Prader-Willi: MR, short stature, hypogonadism, obesity due to decreased satiety peptide YY, paternal interstitial delection chrom 15: 46XY del (15)(q11q13)
+ Universially Maternally imprinted (inactivated) Prader-Willi (Syndrome preventing) genes

Angelman Syndrome "Happy Puppet Syndrome"
MR, seizures, ataxia, inappropriate laughing
maternal interstitial deletion chrom15 +
+ univerally paternally imprinted (inactivated) (Angelman Syndrome preventing) UBE3A gene
male pseudohermaphroditism. What is the most common cause and what are the features of this cause? List additional causes and features where given.
Phen: female w/ normal breasts, bind pouch vagina, no uterus, amenorrhea

Y chrom & testes present but w/ ambiguous-to-female external genitalia or genital ducts

Multiple causes, usually X-linked defective androgen receptor → Testicular feminization aka complete androgen insensitivity sro

Else:
WT gene (chrom 11): Transcriptl Activator for Gonadal & Renal Differentiation
→ defective testicular differentiation
→ Denys Drash: nephropathy, genital ambiguity, Wilm's Pediatric Kidney Tumor
→ WAGR: Wilm's Tumor, genital ambituity risk for gonadoblastoma, aniridia, MR
Defective testicular hormone synth: 17-ketosteroid reductase, 5 alpha reductase
p167
Define female pseudohermaphroditism. What is the most common cause and what are the features of this cause?
XX female w/ AR 21 hydroxylase deficiency → congential adrenal hyperplasia → excess androgen during embryogenesis

→ normal ovaries & internal genitalia, male external genitalia
What defines a true hermaphrodite? What are some causes?
Both ovaries and testes present: either one testis + contralateral ovary or "ovotestis"

Chimera: individuals of 2+ zygotes (us. in vitro fertilization)

Cryptic Chimera: 46XX w/ translocation of Y to autosome

Mosaic: 46XX + 46XY
XYY sro
Excessively Tall Male w/ Severe Acne

[Normal Intelligence, Normal Fertility]
What are the clinical features of Klinefelter syndrome? What is the most common karyotype?
What complications are associated with this Syndrome?
Y + ≥2X, mostly 47XXY's

2° to parental non-disjunction; maternal Ndj 2° to age

Androgen Receptor (located X) contains CAG trinucleotide repeat polymorphism; shorter CAG both more active & preferentially silenced (physiologic in normal XX to use least active androgen receptor) → Sx

hypogonadism w/ severe oligospermia to aspermia, common cause of male infertility

Phen: Long Legs, ↓ IQ (≠MR) & Eunuch-like (gynecomastia, small penis, no virilization)
↑ # X's = ↓ IQ

↑ FSH, ↑ E ± ↓ T

Risks: ↑ 20x extragonadal germ cell tumors & breast CA
Acute Pancreatitis
2 levels:

Acute Interstitial Pancreatitis: Secretory Stasis → Digestion of Adiopse by lipase → fatty acids bind Ca2+ and precipitate into calcium salts. Inflammation and Edema. Lesions are visible on light microscapy.

Acute Necrotic Pancreatitis: abnormal activation of trypsin → cascade of protease activation → autolysis of pancreas & vasculature → white chalky fat + black hemorrhage both grossly visible

Causes: Gallsones, Ethanol, Trauma, Steroids, Mumps, Autoimmunitym Scorpion stings, HyperCalcemia, HyperTAGermia (>1000), ERCP (Endoscopic Retrograde Colangiopancreatography), sulfa Drugs

Mn: GET SMASHED
Trisomy 13
Patau syndrome
uniformly fatal w/in first year, vast majority <1mo
ultimate cause: maternal age

Phen: Cleft Palate, Cleft Lip, Polydacyly, Microcephalus w/ Narrow forehead, closely spaced eyes ± cyclopia, MR, umbilical hernia, rocker bottom feet, IUGR, Inside: Congenitla heart disease, renal defects

Mn: Think P's: cleft Palate, cleft liP, Polydactyly, holoProsencephaly (forebrain dvlpt failure)

Prenatal Screen: low PAPPA, low hCG
[Pregnancy Assoc. Plasma Protein A]
Trisomy 18
Edwards Syndrome usually nondisjunction or mosaic

IUGR
small face to head ratio w/ micrognathia
prominent occiput, low set ears, flat helices
enlarged first finger: overlapping fingers
congenital heart disease
horseshoe kidney
rocker bottom feet
mental retardation
mean survival 2 mo, overwelming majority die in infancy
Unmineralized osteoid matrix
hallmark of ricketts
Alport Sro
X linked Mutation in Type IV Collagen production

Affects: Kidney, Ears, Eyes
(Hear No Evil, See No Evil, Pee No Evil)

Nephritic Sro → Chronic Renal Failure
[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn, & proteinuria <3.5g/d]
Nerve Deafness
Lens Problems (Cataracts, Lens Dislocation, Corneal Dystrophy)

Interestingly: Pts lack the antigen which Goodpasture Sro Antibodies attack
Mutation in Type IV Collagen Production
Alport Sro: X linked Mutation in Type IV Collagen production

Affects: Kidney, Ears, Eyes
(Hear No Evil, See No Evil, Pee No Evil)

Nephritic Sro → Chronic Renal Failure
[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn, & proteinuria <3.5g/d]
Nerve Deafness
Lens Problems (Cataracts, Lens Dislocation, Corneal Dystrophy)

Interestingly: Pts lack the antigen which Goodpasture Sro Antibodies attack
Hematuria w/ RBC Casts
Deafness & Cataracts
Alport Sro: X linked Mutation in Type IV Collagen production

Affects: Kidney, Ears, Eyes
(Hear No Evil, See No Evil, Pee No Evil)

Nephritic Sro → Chronic Renal Failure
[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn, & proteinuria <3.5g/d]
Nerve Deafness
Lens Problems (Cataracts, Lens Dislocation, Corneal Dystrophy)

Interestingly: Pts lack the antigen which Goodpasture Sro Antibodies attack
Berger's Dz
IgA nephropathy, Berger's Dz

Respiratory/GI environmental antigen → abnormal ↑ IgA prodxn → overwhelm's hepatobiliary clearence → glomerular IgA deposition → complement activation → Nephritic Sro

[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn, & proteinuria <3.5g/d]

LM: mesngeial proliferation
EM- IC deposits in mesangium
IF: IgA IC deposits in mesangium

2° IgA nephropathy may be due to celiac dz (Ab overprodxn) or liver dz (↓ IgA Clearance)

NB: Henoch-Schonlein Purpura is a systemic manifestation of the same process: purpuric lesions & arthralgia + some type of renal manifestation
IgA nephropathy
IgA nephropathy, Berger's Dz

Respiratory/GI environmental antigen → abnormal ↑ IgA prodxn → overwhelm's hepatobiliary clearence → glomerular IgA deposition → complement activation → Nephritic Sro

[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn, & proteinuria <3.5g/d]

LM: mesngeial proliferation
EM- IC deposits in mesangium
IF: IgA IC deposits in mesangium

2° IgA nephropathy may be due to celiac dz (Ab overprodxn) or liver dz (↓ IgA Clearance)

NB: Henoch-Schonlein Purpura is a systemic manifestation of the same process: purpuric lesions & arthralgia + some type of renal manifestation
Most Common Cause of Death in SLE
Diffuse Proliferative Glomerulonephritis

LM: Wire Looping of capillaries
EM: subendothelial/intramembranaous IgG based IC's , esp C3
IF: Granular

May present as Nephritic or Nephrotic
2° to SLE or Membranoproliferative Glomerulonephritis
Most common cause of death in SLE

[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn]

[Nephrotic Sro: Massive proteinuria >3.5g/d, hyperlipidemia, fatty casts. Edema from protein loss, Thromoemboli from AT3 loss, infection from Ig loss]
Diffuse Proliferative Glomerulonephritis
Diffuse Proliferative Glomerulonephritis

LM: Wire Looping of capillaries
EM: subendothelial/intramembranaous IgG based IC's , esp C3
IF: Granular

May present as Nephritic or Nephrotic
2° to SLE or Membranoproliferative Glomerulonephritis
Most common cause of death in SLE

[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn]

[Nephrotic Sro: Massive proteinuria >3.5g/d, hyperlipidemia, fatty casts. Edema from protein loss, Thromoemboli from AT3 loss, infection from Ig loss]
Renal Problems

LM: Wire looping of capillaries
Diffuse Proliferative Glomerulonephritis

LM: Wire Looping of capillaries
EM: subendothelial/intramembranaous IgG based IC's , esp C3
IF: Granular

May present as Nephritic or Nephrotic
2° to SLE or Membranoproliferative Glomerulonephritis
Most common cause of death in SLE

[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn]

[Nephrotic Sro: Massive proteinuria >3.5g/d, hyperlipidemia, fatty casts. Edema from protein loss, Thromoemboli from AT3 loss, infection from Ig loss]
Acute Post-Streptococcal Glomerulonephritis
Nephritic/Nephrotic Sro Combo

LM: enlarged & hypercellular glomeruli
EM: subepithelial IC hums
IF: granular deposition of Antibodies and C3

Spontaneous resolution

[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn, & proteinuria <3.5g/d]
[Nephrotic Sro: Massive proteinuria >3.5g/d, hyperlipidemia, fatty casts. Edema from protein loss, Thromoemboli from AT3 loss, infection from Ig loss]
Rapidly Progressive Glomerulonephritis
Rapidly Progressive (Crescenteric) Glomerulonephritis

Nephritic Sro c Poor Px

LM & IF: Crescent moon shape deposits of fibrin and plasma protein with cellularity of Monocytes & M∅

Goodpasture Sro: antibodies to GBM & Alveolar BM → linear IF, hematuria + hemoptysis
Wegener's Granulomatosis: c-ANCA
Microscopic polyangitis: p-ANCA

[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn, & proteinuria <3.5g/d]
By what metabolic process do some drugs induce SLE-like effects
Slow Phase II N-acetylation

genetically determined
Laron dwarfism
defective growth hormone receptors (JAK-STAT)
What is the fundamental defect of β thalassemias
mRNA processing

hypochromia & target cells
Scotoma
area of visual loss surrounded by unimpaired vision

a neurologic result not an anatomic/physiologic finding
Aseptic Hemorrhagic Cystitis in Children
Adenovirus
Ischemic Damage to Kidney:
which area of nephron is damaged
proximal tubule s and thick ascending limb in the outer medulla

apparently the outer medulla has the lowest blood supply normally

also these areas are actively exporting stuff, and so using up ATP and needing O2

NB: Muddy Brown casts are pathognomonic for ATN (which may be ischemic or toxic)
Muddy Brown Casts
pathognomonic for Aute Tubular Necrosis

May be ischemic or toxic
Ankylosing Spondylitis
HLA-B27 assoc chronic inflammatory condition

presents as morning stiffness, esp LBP

∅ ↓ lifespan

Musculoskeletal: enthesitis (tendon insertion inflammation)
Respiratory: limited chest expansion 2° to costal muscle enthesites
Cardiovascular: Ascending aortitis → aortic dilation & insufficiency
Eye: anterior uveities → blurred vision/photophobia
morning stiffness/LBP
HLA-B27
Ankylosing Spondylitis

HLA-B27 assoc chronic inflammatory condition

presents as morning stiffness, esp LBP

∅ ↓ lifespan

Musculoskeletal: enthesitis (tendon insertion inflammation)
Respiratory: limited chest expansion 2° to costal muscle enthesites
Cardiovascular: Ascending aortitis → aortic dilation & insufficiency
Eye: anterior uveities → blurred vision/photophobia
Lipid Laden Macrophages in the skin of the eyelid
Xanthelasma, a form of xanthoma

assoc w/ hyperlipidemia
Xanthelasma
lipid laden macrophages in the skin of the eyelid 2° to systemic hyperlipidemia
Pathogenesis of Marfan Sro
Defect in Fibrillin-1 "elastin assoc. glycoprotein"

most noted in;
1. habitus
2. zona fibers of lens (lens dislocation)
3. large arteries (aortic dissection)
MR, eczema and mousy odor
PKU

AR
Humoral Hypercalcemia of Malignancy
PTHrP
Parathyroid Hromone Related Peptide: closely resembles PTH at bioactive amino temrinal
Dystonia
sustained involuntary contractions 2° to impaired fnx of basal ganglia, eg:

Torticollis
Blepharospasm: uncontrollable blinking/forced closure
Writer's Cramp
Fibrous intimal thickening with endocardial plaques limited to the right heart
characteristic of carcinoid heart dz 2° to carcinoid sro

Canerous production of 5-HT, histamine, Bradykinin, Prostaglandins &/or tachykinins → pulmonary stenosis and/or restrictive cardiomyopathy

degree of cardiac involvement ≈ 5-HT & prodxn

5-HT & bradykining inactivated by pulmonary vascular endothelial monoamine oxidase → no left sided effects

Lab test: 5-hydroxyindoleacetic acid = urinary excretory metabolite of 5-HT
5-hydroxyindoleacetic acid
Fibrous intimal thickening with endocardial plaques limited to the right heart → pulmonary stenosis and/or restrictive cardiomyopathy

characteristic of carcinoid heart dz 2° to carcinoid sro

Canerous production of 5-HT, histamine, Bradykinin, Prostaglandins &/or tachykinins

degree of cardiac involvement ≈ 5-HT & prodxn

5-HT & bradykining inactivated by pulmonary vascular endothelial monoamine oxidase → no left sided effects

Lab test: 5-hydroxyindoleacetic acid = urinary excretory metabolite of 5-HT
cardcinoid heart dz
Fibrous intimal thickening with endocardial plaques limited to the right heart → pulmonary stenosis and/or restrictive cardiomyopathy

2° to carcinoid sro

Canerous production of 5-HT, histamine, Bradykinin, Prostaglandins &/or tachykinins

degree of cardiac involvement ≈ 5-HT & prodxn

5-HT & bradykining inactivated by pulmonary vascular endothelial monoamine oxidase → no left sided effects

Lab test: 5-hydroxyindoleacetic acid = urinary excretory metabolite of 5-HT
Chronic Granulomatous Dz
Chronic Granulomatous Dz

X-linked defict of NADPH Oxidase → inability to kill organism in phagolysosomes → recurrent infx

↑↑↑ Susceptibility to certain catalase positive organism:
--Staph aureus
--Pseudomanas cepacia (burkholderia cepacia)
--Serratia marcescens
--Nocardia
--Aspergillus

PMN's cannot oxidize Nitroblue Tetrazolium: do not stain
Defect of NADPH Oxidase
Chronic Granulomatous Dz

X-linked defict of NADPH Oxidase → inability to kill organism in phagolysosomes → recurrent infx

↑↑↑ Susceptibility to certain catalase positive organism:
--Staph aureus
--Pseudomanas cepacia (burkholderia cepacia)
--Serratia marcescens
--Nocardia
--Aspergillus

PMN's cannot oxidize Nitroblue Tetrazolium: do not stain
PMN's do not stain with Nitroblue Tetrazolium
Chronic Granulomatous Dz

X-linked defict of NADPH Oxidase → inability to kill organism in phagolysosomes → recurrent infx

↑↑↑ Susceptibility to certain catalase positive organism:
--Staph aureus
--Pseudomanas cepacia (burkholderia cepacia)
--Serratia marcescens
--Nocardia
--Aspergillus

PMN's cannot oxidize Nitroblue Tetrazolium: do not stain
liver biopsy sample: extensive lymphocyte infiltration with granulomatous destruction of bile ducts
primary biliary cirrhosis

classically: middle aged cuacasian female with hx pruritis and fatigue who now dvlps pale stool and xanthelasma
middle aged cuacasian female with hx pruritis and fatigue who now dvlps pale stool and xanthelasma
classic picture of primary biliary cirrhosis

liver biopsy sample: extensive lymphocyte infiltration with granulomatous destruction of bile ducts
male with long hx ulcerative colitis presents with fatigue and high alkaline phosphatase
primary sclerosing cholangitis
elderly female with weight loss, abdominal discomfort, jaundice and epigastric mass
pancreatic cancer
homeless malewith fever, abdominal pain and jaundice
acute cholangitis
What signals induce atherosclerotic plaque formatino
Platelet signals:

PDGF: chemotactic and mitogenic for VSMC's

TGF-β: chemotactic for VSMC's
Inheritance of Glaucoma
Polygenic
Inheritance of Epilepsy
Polygenic
Inheritance of Androgenic Baldness
Polygenic
MPO Deficiency
Myeloperoxidase Deficiency

cannot convert H2O2 → ROS's for killing

Similar to Chronic Granulomatous Dz (NADPH deficiency)
most organisms produce H2O2 on their own
CGD catalase positive organisms will survive because H2O2 before MPO can convert it to SOD

In MPO KO all organisms can survive within the phagocytes
Late separation of the umbilical cord,
Recurrent non-puritic skin infx
Gingivitis
Classic Triad of Leukocyte Adhesion Deficiency

AR absence of CD18 necessary to form integrins

Leukocyte migration:
1. Rolling adhesion via E & P Selectins expressed on Endothelium (ligand on WBC)
2. Firm attachment via Integrins expressed on WBC (ligand on Endothelium)
3. Transmigration via PECAM-1 (CD31) expressed on both
CD18 deficiency
Leukocyte Adhesion Deficiency

AR absence of CD18 necessary to form integrins

Classic Triad of Late separation of the umbilical cord,
Recurrent non-puritic skin infx
Gingivitis

Leukocyte migration:
1. Rolling adhesion via E & P Selectins expressed on Endothelium (ligand on WBC)
2. Firm attachment via Integrins expressed on WBC (ligand on Endothelium)
3. Transmigration via PECAM-1 (CD31) expressed on both
Deficiency of late complement components
C5b - C9

no MAC → esp vulnerable to Neisseria
genetic defect: ↑ vunlnerability to Neisseria
Deficiency of late complement componentsC5b - C9

no MAC → esp vulnerable to Neisseria
Hypersegmented PMNs
Indicative of B12 (transcobalamin) deficiency
Primary amenorrhea with fully developed 2° sexual characteristics
Anatomic Defect:
Imperforate Hymen or Mullerian duct abnormalities
Heart Murmur + Bounding Pulses
Aortic Regurgitation

Abnormally high LVSV followed by rapid regurgitant flow into left ventricle → wide pulse pressure

Signs:
"water-hammer" pulses & de Musset's head bob
Heart Murmur + Head Bob
Aortic Regurgitation

Abnormally high LVSV followed by rapid regurgitant flow into left ventricle → wide pulse pressure

Signs:
"water-hammer" pulses & de Musset's head bob
Aortic Regurgitation
Abnormally high LVSV followed by rapid regurgitant flow into left ventricle → Diastolic murmur + wide pulse pressure

Signs:
"water-hammer" pulses & de Musset's head bob
Why don't all lungers with cor pulmonale have edema
passive ↑ in lymphatic flow

no edema until lymphatic flow overwhelmed
Gilbert Sro
Reduced functionality of UDG glucuronyl transferase

AR

episodic unconjugated bilirubinemia following stress w/o ↑ LFT's
episodic jaundice following stress, ∅↑ LFT
Gilbert Sro

AR

Reduced functionality of UDG glucuronyl transferase
Reduced functionality of UDG glucuronyl transferase
Gilbert Sro

AR

episodic unconjugated bilirubinemia following stress w/o ↑ LFT's
Young adult with chronically elevated LFTs
most probable scenario for Wilson's Dz

↓ ceruloplasmin
↑ urinary copper
Kayser-Fleisher rings
Folate Deficiency
THF required for synthesis of
All purines
dTMP (Thymidine)

megaloblastic anemia

phenytoin, sulfas, Methotrexate

reverse with folate
alleviate with thymidine
NB: purines 90% recycled, thymidine synthesis most impaired
ADA KO
Adenosine deaminase (Adenosine → Inosine)
an important step in Purine degradation

Inosine will be degraded to Hypoxanthine
Hypoxanthine may be recycled by HGPRT to IMP or degraded by Xanthine Oxidase (Hypoxanthine → Xanthine → Uric Acid) [same enzyme, 2 steps]

ADA KO results in a mass-action ↑ dATP

dATP inhibits Ribonucleotide Reductase, which is converts NDPs → dNDPs necessary for DNA synthesis

[specifically ADP, UDP, CDP and GDP → dADP, dUDP, dCDP, dGDP]

worst hit cells: rapidly proliferating lymphocytes
→ 2nd most common form of SCID (AR)
(most common form: X linked deficiency of γ chain necessary for T lymphoblast response to IL7 survival signal in thymus)
Exertional Dyspnea
PAS+ Cytoplasmic inclusions on Liver Biopsy
globules of unsecreted α1 antitrypsin in periportal hepatocytes

→ cirrhosis & hepatocellular carcinoma

→ para-acinar emphysema emphysema
Intranasal ulceration, Sudden Onset Oliguria
Wegener's Granulomatosis
antineutrophil cytoplasmic antibodies c-ANCA's
→ rapidly progressive (crescenteric) glomerulonephritis

Nephritic Sro w/ poor px

NB: hemoptysis indicative of Goodpasture Sro
anti-neutrophil antibodies
Wegener's Granulomatosis
antineutrophil cytoplasmic antibodies c-ANCA's
→ rapidly progressive (crescenteric) glomerulonephritis

Nephritic Sro w/ poor px

NB: hemoptysis indicative of Goodpasture Sro
hematuria + hemoptysis
Goodpasture Sro
hematuria + hemoptysis

antibodies to GBM and alveolar basement membrane
→ rapidly progressive (crescenteric) glomerulonephritis

Nephritic Sro w/ poor px

linear Immunofluorescence

NB: mucosal uceration typical of Wegener's w/ antineutrophil cANCA's
Goodpasture Sro
hematuria + hemoptysis
Myotonic Dystrophy
CTG trinucleotide expansion within myotponia protein kinase

AD inheritance

Cataracts & Myotonia
Myotonia: unwanted sustained muscle contractions
--cannot release doorhandles
Type 1 fibers more affected

Also: frontal balding & gonadal atrophy

differentiate from Duchenne: Myotonic Dystrophy does not have necrosis of muscle fiber sand fibrofatty replacement
Pre-schooler comes to stand by spreading legs and walking his hands backwards
Gower's Sign of Duchenne Muscular Dystrophy

X linked frameshift → nonsense mutation within dystrophin gene

dystrophin anchors skeletal and muscle fibers → accelerated muscle breakdown

starts in pelvic girdle → progresses superiorly

Onset <5yo
pseudohypertrophy of calves 2° fibro-fatty replacement

Dx: ↑CPK and muscle biopsy: necrosis and fibrofatty replacement
Dystrophin Gene Mutation
dystrophin anchors skeletal and muscle fibers → accelerated muscle breakdown
X linked frameshift → nonsense mutation → Duchenne's Muscular Dystrophy

starts in pelvic girdle → progresses superiorly

Onset <5yo
pseudohypertrophy of calves 2° fibro-fatty replacement
Gower's sign: coming to a stand via spreading legs apart and "walking" backwards on their hands so as not to need lower extremities

Dx: ↑CPK and muscle biopsy: necrosis and fibrofatty replacement
↑ CPK

muscle biopsy with fibrofatty replacement
Duchenne's Muscular Dystrophy

X linked frameshift → nonsense mutation within dystrophin gene

dystrophin anchors skeletal and muscle fibers → accelerated muscle breakdown

starts in pelvic girdle → progresses superiorly

Onset <5yo
pseudohypertrophy of calves 2° fibro-fatty replacement
Gower's sign: coming to a stand via spreading legs apart and "walking" backwards on their hands so as not to need lower extremities

Dx: ↑CPK and muscle biopsy: necrosis and fibrofatty replacement
What is the mechanism by which Systemic Hypertension produces Pulmonary Hypertension
systemic hypertension → Left Ventricular Failure → Pulmonary Congestion ie ↑ Hydrostatic pressure → Edema → reactive vasoconstriction

reactive vasoconstrxn normally physiologic to direct blood towards more oxygenated areas. With whole lung edema creates pulmonary htn
Giant Cell Arteritis
aka Temporal Arterities

>50 yo with headaches and jaw claudication
late stages visual impairment

Pathogenesis: granulomatous inflam of large arteries, esp Tempral

NB: looks just like Takayasu's Pulseless Arterities, except that one affects the aorta and great vessels <50yo
Takayasu's Dz
aka Pulseless Dz

<50 yo with extremely weak Carotid/UE pulses (palpable LE pulses)

Granulomatous obliteration of aorta & great vessels

NB: same histology as Giant Cell temproal arteritis, except that dz affects medium sized vessels >50 yo
Pt has extremely weak Carotid, UE pulses
Takayasu's Arteritis, aka Pulseless Dz

<50 yo with extremely weak Carotid/UE pulses (palpable LE pulses)

Granulomatous obliteration of aorta & great vessels

NB: same histology as Giant Cell temproal arteritis, except that dz affects medium sized vessels >50 yo
Polyarteritis Nodosum
Chronically ongoing inflammation of medium & small arteries

Segmentally distinct acute inflam → Mixed WBC infiltrate → Fibrinoid necrosis
(Contrast Mixed WBC Infitlrate to eosinophil dominated Churgg-Strauss, and PMN dominanted -ie leukocytoclastic- Microscopic polyangitis)

Histology: thick hyalinosis in adventitia

All stages concurrent around the body
(Contrast to Kawasaki's lock-step progression)

Not assoc with ANCA's
(Contrast to Wegener's and Microscopic Polyangitis)

Fatal if UnTx
Rx: immunosuppressents
Arterial Biopsies from different locations in different stages of acute inflammation and healed fibrinoid necrosis
Polyarteritis Nodosum; Chronically ongoing inflammation of medium & small arteries

Segmentally distinct acute inflam → Mixed WBC infiltrate → Fibrinoid necrosis
(Contrast Mixed WBC Infitlrate to eosinophil dominated Churgg-Strauss, and PMN dominanted -ie leukocytoclastic- Microscopic polyangitis)

Histology: thick hyalinosis in adventitia

All stages concurrent around the body
(Contrast to Kawasaki's lock-step progression)

Not assoc with ANCA's
(Contrast to Wegener's and Microscopic Polyangitis)

Fatal if UnTx
Rx: immunosuppressents
Wegener's Dz
Wegener's Granulomatosis
c-ANCA assoc (PR3 ANCA)

Classic triad:

Acute, Cavitating, Necrotizing Granulomas of RespiratoryTract

Necrotizing Vasculitis of Small and Medium Vessels with Ulceration of Pharynx

Rapidly Progressive (Crescenteric) Glomerulonephritis (hypercellularity of parietal cell layer)

[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn, & proteinuria <3.5g/d]

Poor Px
c-ANCA
Wegener's Granulomatosis
c-ANCA assoc (PR3 ANCA)

Classic triad:

Acute, Cavitating, Necrotizing Granulomas of RespiratoryTract

Necrotizing Vasculitis of Small and Medium Vessels with Ulceration of Pharynx

Rapidly Progressive (Crescenteric) Glomerulonephritis (hypercellularity of parietal cell layer)

[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn, & proteinuria <3.5g/d]

Poor Px
Ulceration of Pharyngeal Mucosa

Acute Onset Oliguria
Wegener's Granulomatosis
c-ANCA assoc (PR3 ANCA)

Classic triad:

Acute, Cavitating, Necrotizing Granulomas of RespiratoryTract

Necrotizing Vasculitis of Small and Medium Vessels with Ulceration of Pharynx

Rapidly Progressive (Crescenteric) Glomerulonephritis (hypercellularity of parietal cell layer)

[Nephritic Sro: Inflammation → RBC Cast Hematuria, Azotemia, Oliguria, Na+ retaining Htn, & proteinuria <3.5g/d]

Poor Px
Buerger's Dz
Buerger's Thromboangitis Obliterans

Cigarette Smoking <35 yo

Sharply segmental vasculitis of medium & small arteries

Toxicity of Tobacco or Immune Response to Contents

Severly painful episodes of ischemia
Young Adult Smoker with Sharp Pain in Hands
Buerger's Thromboangitis Obliterans

Cigarette Smoking <35 yo

Sharply segmental vasculitis of medium & small arteries

Toxicity of Tobacco or Immune Response to Contents

Severly painful episodes of ischemia
Kawasaki's Dz
Young Children <4yo produce autoantibodies to endthlium

presents as acute febrile illness

acute inflammation and fibrinoid necrosis
unlike Polyarteritis nodosum: occurs all around body in lock step (no simultaneous presentation of different phases)

Fibrinoid necrosis w/ predilicition for coronary arteries → aneurysm → death

Rx: IVIg's & Aspirin
Microscopic Polyangitis
Microscopic Polyangitis aka leukocytoclastic vasculitis

mostly ANCA assoc.

Arterioles, Capillaries, Venules

usually only PMN's seen (thus leukocytoclastic vasculitis)
Churg Strauss Dz
Hyperallergic Response Vasculitis (to unknown antigen)

Classic Quartet
Eosinophilia
Asthma
Necrotizing Vasculitis of Small Vessels
Granulomas Extravascular

Precipitated by Leukotriene Receptor Antagonists in Asthmatics
leukocytoclastic vasculitis
Microscopic Polyangitis aka leukocytoclastic vasculitis

mostly ANCA assoc.

Arterioles, Capillaries, Venules

usually only PMN's seen (thus leukocytoclastic vasculitis)
Vasculitis of Arterioles, Capillaries, and Venules
Microscopic Polyangitis aka leukocytoclastic vasculitis

mostly ANCA assoc.

Arterioles, Capillaries, Venules

usually only PMN's seen (thus leukocytoclastic vasculitis)
Vasculities with only PMNs visible on biopsy
Microscopic Polyangitis aka leukocytoclastic vasculitis

mostly ANCA assoc.

Arterioles, Capillaries, Venules

usually only PMN's seen (thus leukocytoclastic vasculitis)
Vasculitis with Eosinophilia
Churg Strauss Dz, aka Hyperallergic Response Vasculitis (to unknown antigen)

Classic Quartet
Eosinophilia
Asthma
Necrotizing Vasculitis of Small Vessels
Granulomas Extravascular

Precipitated by Leukotriene Receptor Antagonists in Asthmatics
Vasculitis following Leukast Administration
Churg Strauss Dz, aka Hyperallergic Response Vasculitis (to unknown antigen)

Classic Quartet
Eosinophilia
Asthma
Necrotizing Vasculitis of Small Vessels
Granulomas Extravascular

Precipitated by Leukotriene Receptor Antagonists in Asthmatics
Febrile Illness in Preschooler leads to Coronary Aneurism
Kawasaki's Dz

Young Children <4yo produce autoantibodies to endthlium

presents as acute febrile illness

acute inflammation and fibrinoid necrosis
unlike Polyarteritis nodosum: occurs all around body in lock step (no simultaneous presentation of different phases)

Fibrinoid necrosis w/ predilicition for coronary arteries → aneurysm → death

Rx: IVIg's & Aspirin
Abnormally High HbA2
α2δ2

indicative of β thalassemia trait
The most sure sign of irreversible cell linjury
mitochondrial vacuolization
Mitochondrial Vacuolization
the most sure sign of irreversible cell injury
Wilsons's Dz
Wilson's Dz: Mutation of ATPB7 on chrom 13

ATPB7: ATP dependent copper transporter responsible for getting copper into the right place where it can be bound with ceruloplasmin or excreted in bile

excess copper builds up in liver → liver toxicity

long latent period until copper overwhelms liver → Systemic Manifetations

Asterixis
Damage to Basal Ganglia: dysarthria, parkinsonian like rigidity
Kayser-Fleischer Rings around the iris
Hemolysis

Dx: Slit lamp examination demonstrates kayser fleischer rings
Tx: penicillamine
Cure: Liver transplant
ATPB7
Wilson's Dz: Mutation of ATPB7 on chrom 13

ATPB7: ATP dependent copper transporter responsible for getting copper into the right place where it can be bound with ceruloplasmin or excreted in bile

excess copper builds up in liver → liver toxicity

long latent period until copper overwhelms liver → Systemic Manifetations

Asterixis
Damage to Basal Ganglia: dysarthria, parkinsonian like rigidity
Kayser-Fleischer Rings around the iris
Hemolysis

Dx: Slit lamp examination demonstrates kayser fleischer rings
Tx: penicillamine
Cure: Liver transplant
Young Adult with New Onset Bradykinesia, Dysarthria
Wilson's Dz: Mutation of ATPB7 on chrom 13

ATPB7: ATP dependent copper transporter responsible for getting copper into the right place where it can be bound with ceruloplasmin or excreted in bile

excess copper builds up in liver → liver toxicity

long latent period until copper overwhelms liver → Systemic Manifetations

Asterixis
Damage to Basal Ganglia: dysarthria, parkinsonian like rigidity
Kayser-Fleischer Rings around the iris
Hemolysis

Dx: Slit lamp examination demonstrates kayser fleischer rings
Tx: penicillamine
Cure: Liver transplant
Keyser-Fleischer
Wilson's Dz: Mutation of ATPB7 on chrom 13

ATPB7: ATP dependent copper transporter responsible for getting copper into the right place where it can be bound with ceruloplasmin or excreted in bile

excess copper builds up in liver → liver toxicity

long latent period until copper overwhelms liver → Systemic Manifetations

Asterixis
Damage to Basal Ganglia: dysarthria, parkinsonian like rigidity
Kayser-Fleischer Rings around the iris
Hemolysis

Dx: Slit lamp examination demonstrates kayser fleischer rings
Tx: penicillamine
Cure: Liver transplant
Homocysteinuria
Cystathionine synthase deficiency
Marfanoid Habitus and Thromboemboli

--Homocysteine produced as end product of SAM usage
--Methionine Synthase aka Homocysteine methyltransferase[B12] (Homocysteine + N5-methyl-THF → Methionine)
--Methionine + ATP → SAM
--Methyltransferase(SAM → S-adensoyl homocysteine + methyl group on other subtrate)
--Unimportant enzyme (SAH → Homocysteine & Adenosine)
--at this point Homocysteine may be recycled or

Cystathione synthetase[B6](Homocysteine + Serine → Cystathione
Csystathionase[B6](Cystathione → Cysteine)

1/2 of pts respond positively to B6 supplementation
(↑ functionality of poorly functioning cystathione synthetase)
Young Child with Thromboembolitic Infarcts in Various stages of healing
Homocysteinuria: Cystathionine synthase deficiency
Marfanoid Habitus and Thromboemboli

--Homocysteine produced as end product of SAM usage
--Methionine Synthase aka Homocysteine methyltransferase[B12] (Homocysteine + N5-methyl-THF → Methionine)
--Methionine + ATP → SAM
--Methyltransferase(SAM → S-adensoyl homocysteine + methyl group on other subtrate)
--Unimportant enzyme (SAH → Homocysteine & Adenosine)
--at this point Homocysteine may be recycled or

Cystathione synthetase[B6](Homocysteine + Serine → Cystathione
Csystathionase[B6](Cystathione → Cysteine)

1/2 of pts respond positively to B6 supplementation
(↑ functionality of poorly functioning cystathione synthetase)
polymicrogyria
small gyri → MR

assoc. w/ arnold chiari
Arnold Chiari Malformation
Posterior fossa is too small: not enough space for the cerebellum

Components:
Type 2: hydrocephalus and spina bifida you must correct clinically
--malformed midline cerebellum: vermis extends thru foramen magnum;
--aquaductal stenosis, hydrocephalus, hydromyelia (enlarge central canal)
--kinked medulla oblongata
--herniated cerebellar tonsils
--broken qudrigeminal plate
--spina bifida c lumbar myelomenigocele
--displaced brain c pressure atrophy
--assoc: polymicroyria, aqueductal stenosis, cerebral heterotopias, hydromyelia

Type 1: sphingomyelia, loss of heat and pain
cerebellar tonsils hang into vertebral canal → adult onset HA & Ataxia
HNPCC
AD defect in DNA proofreading and mismatch repair

Colon, endometrial & ovarian cancers
Defective enzyme in DNA proofreading and mismatch repair
HNPCC

AD

Colon, endometrial & ovarian cancers
Prolactinomas
prolactin suppresses GnRH prodxn → hypogonadism
risk for osteoporosis in women

indolent tumor, mostly present in women <10mm as amenorrhea, in men as >10mm (micro vs macro) but still indolent