Genetics Flashcards
1
Q
Start vs Stop Codons
“U Go Away, U Are Away, U Are Gone”
A
AUG (MET)
UGA, UAA, UAG
2
Q
Process of protein synthesis key points
Initiation
Elongation
Termination
A
Initiation:
–> eIF id 5’cap & assemble 40S, eIF’s release & 60S is assembled with ATP (Chraging) & GTP (Translocation)
Elongation:
–> Aminoacyl-tRNA binds A site & rRNA catalyzes growing peptide bond + adds peptides
–> Ribosome moves 3 nucleotides to 3’ end or mRNA bringing the tRNA to P site
Termination:
–> eRF’s id stops codon & stop translation, the finished polypeptide is released (via GTP) from E site
3
Q
APE of protein synthesis
A
A: Aminoacyl-tRNA
P: Peptide grows
E: Empty tRNA Exits
4
Q
Shine-Daigarno sequence
A
A prokaryotic ribosomal binding site that aligns ribosomes to a start codon
5
Q
Which bacteria target eIFs in protein synthesis via bacterial endo/exotoxins to interfere with protein formation?
A
Diptheria & Pseudomonas
6
Q
Post Translational Modification
Trimming
Covalent alteration
Chaperone
A
Trimming:
–> Remove N or C terminal peptides to make a mature protein
Covalent Alt:
–> Phosphorylation, Hydroxylation, Glycosylation, methylation, acetylation, & ubiquitination
Chaperone:
–> Intracellular proteins to facilitate/maintain protein folding/denaturation (heat shock proteins in yeast)
Ex. Cystic fibrosis
7
Q
Cell types:
Permanent
Stable/Quiescent
Labile
A
Perm:
Stuck in G0 (neurons, skeletal, cardiac, RBC)
S/Q:
Can go from G1–>G0 ( Hepato, lympho cytes, PCT, Periosteal cells)
Labile:
Always dividing ( Bone marrow, gut epi, skin/hair/germ cells)
8
Q
Cell cycle
&
Regulators (3)
A
Reg:
Cyclin-dep kinases
Cyclin-CPK complexes (Phosphorylate Rb)
Tumour suppressors (P53)
9
Q
Cell Trafficking (RER—> Golgi) processes
COPS I&II Function
A
“2 steps forward, 1 step back”
COPII –Anterograde–> Cis Golgi –> Trans golgi–> Lysosomes (destroyed) OR plasma membrane (via LDL receptors)
10
Q
RER
VS.
SER
What’s made & gen characteristics?
A
RER:
Secretory hormone synthesis
N-linked oligosaccharide addition to lysosomal proteins
Nissle bodies to make peptide neurotransmitters
SER:
Steroid hormone synthesis
Detox site
Has Glu-6-phosphatase (glycogenolysis/gluconeogenesis)
11
Q
O-Oligosaccharides functions (3)
A
- N-oligosaccharide on asparagine
- Adding O-oligosaccharide on serine+threonine
- Adding Mannose-6-phosphate to proteins
12
Q
Lysosomal Storage disorders: AR
Lysosomal enzyme deficiency accumulation of abnormal metabolic products.
A
I cell disease
Fabrys
Gauchers
Krabes
Metachromatic leukodystrophy
Nieman Picks
Tay Sachs
13
Q
Peroxisome associated disorders
A
Zellweger syndrome
Refsum disease
Adrenolenkodystrophy
14
Q
I-Cell disease
A
Def N-acetylglucoasminyl-1-phosphotransferase reduces mannos-6-phosphaste
Lysosomes lack enzymes to break shit down causing a build-up of debris & high levels of lysosomal enzymes in the blood
Signs:
Coarse facial hair
Gingival hyper plasia
Corneal clouding
Claw hand
Kyphosis
Fatal in childhood
15
Q
Zellweger syndrome
A
AUTO REC
Mutated PEX genes
Signs:
Hypotonia
Seizures
Hepatosplenomegaly
Early death
16
Q
Refsum disease
A
AUTO REC
Def a-oxidation & high phytanic acid
Signs:
Scaly skin
Ataxia
Cataracts/Night blindness
Short 4th toe
Epiphyseal displacement
Rx Diet + plasmapheresis
17
Q
Adrenoleukodystrophy
A
X-linked
Mutated ABCD1 gene =
Disordered B-oxidation causing high levels of very-long-chain fatty acids in adrenals
Signs:
White (leuko) matter in brain & testes
Adrenal crisis
Progressive loss of neurological function
Death
18
Q
Cytoskeleton features
Microfilaments
Intermediate filaments
Microtubes
A
Microfil:
–> Muscle contraction, cytokinesis, actin, & microvilli
Int:
–> Cell structure, vimentin, desmin, & laminins,
Microtubules:
–> Movement (cilia, flagella, mitotic spindle) & axonal trafficking centrioles
19
Q
Dynein vs Kinesin
“REaDY? AttacK!”
“Negative Near Nucleus, Positive Points to Periphery)
A
Retrograde + —> - via dynein
Anterograde - —> + - via kinesin
20
Q
Which bacteria/viruses (3) use dynein for retrograde transport to the neuronal cell body?
A
C. tetani, Poliovirus, & HSV
21
Q
Medications that act upon microtubules
“Microtubes Get Constructed Very Terribly”
A
Mebendazole (anthelminthic)
Griseofulrin (antifungal)
Colchicine (anti-gout)
Vinca alkaloids (anti-cancer)
Taxanes (anti-cancer)
22
Q
What type of cellular junction allows coordinated ciliary movement?
A
Gap junctions
23
Q
Kartagener syndrome
“Kylie Jenner can’t shake ass”
A
AUTO REC
Dynein arm defect = immobile cilia
Signs:
Developmental delays
Hearing loss
Recurrent infections
Infertility
24
Q
Sodium-potassium pump works by moving.
What cardio glycosides directly inhibit the NA/K pump, thereby indirectly increasing heart contractility
A
2 K+ in
3 Na out
Digitoxin & Digoxin
25
Collagen types
1,2,3,4
"SCAB"
I: Skeleton (Bone, tendon, skin) --> Osteogenesis imperfecta 1
II: Cartilage (hyalin)
III: Arteries --> Elhers-Danlos (threED)
IV: Basement membranes --> Alport syndrome + GoodPastures
26
Collagen synthesis process
Collagen synthesis disorders
Scurvy (vit C)
Osteogenesis imperfecta
Menkes
27
Scurvy
Vitamin C deficiency:
Can’t hydroxylate proline/lysine for collagen synthesis
Tea and toast diet
Signs:
Swollen gums
mucosal bleeding
poor wound healing
petechiae
28
Osteogenesis imperfecta
"BITE"
AUTO DOM
Defective COL1A1 or COL1A2 gene = alters the triple helix formation of collagen.
Bones (many fractures/deformities)
I (eye, Blue sclera)
Teeth (dental imperfections)
Ear (Conductive hearing loss
29
Elher-Danlos syndrome
AUTO DOM/REC
Classical: def V collagen (basement membranes)
- Hypermobile joints
- Hyperflexible skin
- Easy bruising
- Mutated CO5A1 or COL5A2
Vascular: def III collagen (Arteries)
- Berry aortic aneurysm
- Muscle/organ/artery are rupture-prone
-Mutated COL3A1
30
Menkes Disease
X-linked REC
Defective ATP7A gene causing low Cu2+ to be present for lysyl oxidase
Signs:
Brittle-Kinky hair
Developmental delay
Hypotonia
Risk of cerebral aneurysms
31
Goodpasture syndrome
2 complications
The linear appearance of IgG deposition on glomerular and
alveolar basement membranes
Can cause:
Glomerulonephritis and hemoptysis via Anti–glomerular basement membrane antibodies
32
Elastin is different from collagen due to the high amounts of what?
Unhydroxylated proline, glycine, & lysine residues
33
How does aging impact collagen, elastin, & cross-linking levels?
Collagen & elastin synthesis is reduced
Cross-linking levels stay normal
34
Marfan's Syndrome
"FFF"
AUTO DOM
Mutated chromosome Fifteenth on the FBN1 gene
Defective Fibrillin
Signs:
"MARFANS"
Main:
*Tall/long arms/flat feet
*Mitral regurgitation
*Aortic root aneurysm
* pNeumothorax
*Arachnodactyly
Hypermobile joints
Up/out lens dislocation
Other:
Pigeon chest
Mitral valve prolapse
35
Homocystinuria
AUTO REC
Signs:
*Joint Hyperlaxity
*Skin hyperelasticity
*Down/out lens dislocation
* Thrombosis
* Impaired intellect
Other:
Pigeon chest
Scoliosis
Tall/long arms
Arachnodactyly
36
Blotting
"SNoW DRoP"
Southern:DNA (Pedigrees)
Northern: RNA (mRNA/gene expression)
Western: Proteins (labelling antibody to find proteins)
SouthWestern: DNA-binding proteins (Leucine zipper motif/DNA probes)
37
Flow cytometry
Assess the size, granularity, & protein expression.
i.e Leukemia, paroxysmal nocturnal hemoglobinuria, & fatal RBCs) & Immunodeficiency (HIV/AIDs)
38
Microarrays
Compares the expression of genes in two diff samples i.e SNP u CNVs (copy # variants)
39
ELISA
Tests for specific antigens/bodies
i.e HIV
40
Karyotyping
Colchicine stops chromosomes in metaphase
41
Fluorescence in situ hybridization:
Microdeletion
Translocation
Duplication
Microdeletion: no fluorescence on an X
Translocation: Fluorescence signal of one X on another X
Duplication: Trisomy (XXX)
42
Gene expression modification
Knock in
Knock out
Random insertion (constitutive expression)
Targeted insertion (conditional expression)
43
RNA interference
microRNA
small interfering RNA
miRNA: Hairpin structures that block translocation & increase degradation of mRNA (Suppressing P53 mRNA = Tumor malignancy)
siRNA: Specific mRNA targeting, meaning it cleaves mRNA before translocation (knockdown exp)
44
Genetics
Codominance
Variable expressivity
Incomplete penetrance
Pleiotropy
Codominance: Both alleles influence the phenotype
- Blood types
- a-Antitrypsin def
- HCA groups
Variable exp: Persons with the same genotype express the mutant phenotype
-Neurofibromatosis type 1
Incomplete pen: Not all people with the genotype express the mutant phenotype
- BRCA1 gene (only always breast/ovarian cancer)
%penetrance x inheritance probability = risk of phenotype
Pleiotropy: One gene contributes to many phenotypes
- PKU (light skin, intellectual disorder, & musty odour)
45
Genetics
Anticipation
Loss of heterozygosity
Dominant Neg mutation
Anticipation: worse severity/earlier onset of a disease in upcoming generations (trinucleotide repeats)
- Huntingtons
Loss of heterozygosity: Patient/develops a mutation in the tumor suppressor gene, then the wild-type gene needs to be deleted as well
- Cancer
- Retinoblastoma
- Lynch syndrome
- Li-Fraumeni syndrome
Dom Neg Mut: Heterozygote makes a non-functional altered protein that prevents the normal gene product from working
- 1 Mutated P53 = Protein binds DNA & blocks non-mutated P53 from binding the promoter)
46
Genetics
Linkage disequilibrium
Mosaicism
Linkage disequilibrium: Certain alleles at 2 linked loci happen more/less often than expected
Mosaicism: Genetically distinct cell lines in the same person, Somatic (mutation via mitotic errors post-fertilization) & Gonadal (mutation ONLY in egg or sperm) PICTURE
47
Hardy Winberg Equations
AA
Aa
aa
X-linked Rec
AA= P^2
Aa= 2Pq
aa= q^2
X-REC:
Male q
Female q^2
48
Imprinting disorders:
Prader-Willi Syndrome
"POP"
Deleted Maternal genes & deleted or mutated Parental X15
Signs:
Obesity
Hyperplasia
Intellectual disability
Hypogonadism
Hypotonia
49
Imprinting disorders:
Angelman Syndrome
"MAMAS"
The paternal UBE3A gene is silenced & maternal allele is deleted/mutated on X15.
Signs:
Ataxia
Inappropriate laughter
Intellectual disability
Seizures
50
Modes of inheritance:
AUTO DOM (1/2 Aa-aa, or 3/4 Aa-Aa)
51
Modes of inheritance :
AUTO REC
parents both A/a =1/4 aa, 1/4AA, 1/2 Aa
Note is a person's sibling is aa their chance of being A/a is 2/3
52
Mode of inheritance:
X-linked REC
Mom --> son 50%
No dad --> son
Usually effects males
53
Mode of inheritance:
X-linked Dom
Mom --> all 50%
Dad --> Daughters
54
Mode of inheritance:
Mitochondrial inheritance
From mom ---> daughters 50%, sons 100%
Affected daughters offspring 100% phenotype
55
Mitochondrial inheritance disorders
MELAS & Leber Hereditary optic neuropathy
56
MELAS (Mitochondrial encephalopathy lactic acidosis & stroke-like episodes)
*RAGGED-RED FIBERS
Myopathy
Lactic acidosis
CNS issues
57
Leber Hereditary Optic Neuropathy (LHON)
Subacute bilateral vision loss
Neurological dysfunction
Cardiac conduction defects
58
List of AUTO DOM diseases:
A
A
F
F
H
H
H
L
M
M
M
N
N
T
Achondroplasia
Autosomal dominant polycystic kidney disease
Familial adenomatous polyposis
Familial hypercholesterolemia
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu
syndrome)
Hereditary spherocytosis
Huntington disease
Li-Fraumeni syndrome
Marfan syndrome
Multiple endocrine neoplasias
Myotonic muscular dystrophy
Neurofibromatosis type 1 (von Recklinghausen disease)
Neurofibromatosis type 2
Tuberous sclerosis,
von Hippel-Lindau disease
59
List of AUTO REC Diseases:
"Oh, Please! Can Students Who Score High Grades Tell Me Features of the Kidney disorder Autosomal Recessive Polycystic Kidney Disease? "
Oculocutaneous albinism
Phenylketonuria
Cystic fibrosis
Sickle cell disease
Wilson disease
Sphingolipidoses (except Fabry disease)
Hemochromatosis
Glycogen storage diseases
Thalassemia
Mucopolysaccharidoses (except Hunter syndrome)
Friedreich ataxia
Kartagener syndrome
ARPKD (Auto REC Polycystic Kidney Disease)
60
X-linked REC disorder list:
B
D/B
G
H
H
L
O
O
O
W
Bruton agammaglobulinemia
Duchenne and Becker muscular dystrophies
Fabry disease
G6PD deficiency
Hemophilia A and B
Hunter syndrome
Lesch-Nyhan syndrome
Ocular albinism
Ornithine transcarbamylase deficiency
Wiskott-Aldrich syndrome
61
Cystic Fibrosis
AUTO REC
Defective CFTR on X7 with a commonly deleted Phe508 (Europeans esp)
Signs:
Recurrent pulmonary infections
Nasal polyps
Pancreatic insufficiency
Infertility
Positive Cl- sweat test
62
Duchenne Muscular Dystrophy
X-linked REC (usually frameshift mutations)
Deleted Dystrophin
Signs:
Weak pelvic girdle muscles
Calve pseudohypertrophy
Dilated cardiomyopathy
Growers sign (needs hands to stand up)
Lordosis
High Creatine Kinase & Aldolase llevels
63
Becker muscular dystrophy
"Becker is Better" less severe.
X-linked (non-frameshift mutation)
Partially functional dystrophin
64
Myotonic dystrophy
"CTG"
AUTO DOM
Onset 20-30yrs
Trinucleotide repeats
Signs:
CTG (Cataracts, Toupee (male balding, Gonadal atrophy)
Arrhythmia
Myotonia
Muscle wasting
65
Rett Syndrome
"retturned"
Usually impacts females (males die in utero) on the X chromosome
onset age 1-4yrs
Signs:
Regression of motor, verbal, and cognitive abilities
Ataxia
Seizures
Hand wriggling
66
Fragile X Syndrome
X-linked DOM
Trinucleotide repeats in the FMR1 (CGG repeat during oogenesis)
Signs:
Intellectual disability
(50-200 repeats) - premature (tremor, ataxia, primary ovarian insufficiency)
(>200 repeats) - full mutation (post-pubertal macrochidism, long face, large jaws, large/high ears, hypermobile joints, & self mutilation)
67
Trinucleotide repeat disorders:
Show genetic anticipation with high disease severity & lower age of onset
Huntingtons (CAG)
Myotrophic dystrophy (CTG)
Fragile X Syndrome (CGG)
Friedrich ataxia (GAA)
68
AUTO trisomies:
Down Syndrome
AKA Trisomy 21
Markers (Hi)
- High hCG & inhibin
5 A's
Advanced maternal age (risk)
Atresia (duodenal)
Atrioventricular septal defect
Alzheimers (early-onset)
AML/ALL (X21 encodes amyloid precursor protein)
Other signs:
Single palmar crease
Hirchsprungs disease
Brush field spots (white spots in the iris peripheral)
Intellectual disability
69
AUTO trisomies:
Edwards Syndrome (18)
"PRINCE-edwards"
Prominent occiput
Rocker-bottom feet
Intellectual disability
Non-disjunction
Clenched fists/overlapping fingers
Ears are low-set
Other:
Micrognathia (small jaw)
Congenital heart disease
Omphalocelegocele
Myelomeningocele
Death ~1yr
70
AUTO trisomies:
Patau Syndrome
Trisomy 13
Signs: Mid Line defects
Cutis aplasia
Severe intellectual disability
Rocker-bottom feet
Microphthalmia
Microcephaly
Cleft lip/palate
Holoprosencephaly
Polycystic kidney disease
Omphalocele
Death ~1 yr
71
Trisomy Screening
72
Trisomies:
3
4
5
6
3 von Hippel-Lindau disease, renal cell carcinoma
4 ADPKD (PKD2), achondroplasia, Huntington disease
5 Cri-du-chat syndrome, familial adenomatous polyposis
6 Hemochromatosis (HFE)
73
Trisomies:
7
9
11
13
7 Williams syndrome, cystic fibrosis
9 Friedreich ataxia, tuberous sclerosis (TSC1)
11 Wilms tumor, β-globin gene defects (eg, sickle cell disease, β-thalassemia), MEN1
13 Patau syndrome, Wilson disease, retinoblastoma (RB1), BRCA2
74
Trisomies:
15
16
17
18
15 Prader-Willi syndrome, Angelman syndrome, Marfan syndrome
16 ADPKD (PKD1), α-globin gene defects (eg, α-thalassemia), tuberous sclerosis (TSC2)
17 Neurofibromatosis type 1, BRCA1, TP53 (Li-Fraumeni syndrome)
18 Edwards syndrome
75
Trisomies:
21
22
X
21 Down syndrome
22 Neurofibromatosis type 2, DiGeorge syndrome (22q11)
X Fragile X syndrome, X-linked agammaglobulinemia, Klinefelter syndrome (XXY)
76
Robertsonian translocation:
Usually involves 21, 22, 13, 14, & 15
Balanced vs. unbalanced
Balanced: no gain/loss of genetic material (no abnormal phenotype)
Unbalanced: missing/extra genes (abnormal phenotype i.e down/patau syndromes)
77
Cri-du-chat syndrome
Congenital deletion of the short arm of chromosome 5 (46XX or XY)
Signs:
Microencephaly
Mod-severe intellect disability
High-pitched crying
Epicanthal folds
Ventral Septal Defect
78
Williams Syndrome
Congenital microdeletion of the long arm of chromosome 7 (induces elastin gene)
Signs:
Elfin facies
Well-developed verbal skills
Intellectual disabilities
Hypercalcemia
Cardiovascular issues (supravalvular aortic
stenosis, renal artery stenosis)
79
Essential fatty acids are
Polyunsaturated & not made by the body
- Linoleic acid (Omega 3) => Cardiprotective cardioprotective + antihyperlipidemic effects
- Linoleic acid (Omega 6) => metabolized to arachidonic acid (leukotrienes/prostaglandins)
80
Fat-soluble vitamins
"DrAKE"
Absorption via the ileum
Patients can have deficiencies from malabsorption syndromes & steatorrhea (i.e. cystic fibrosis or celiacs), or mineral oil intake can cause fat-soluble vitamin deficiencies
81
List of water-soluble vitamins:
B1
B2
B3
B5
B6
B7
B9
B12
C
B1 (thiamine, TPP)
B2 (Riboflavin, FAD & FMN)
B3 (Niacin, NAD)
B5 (Pantothenic acid, CoA)
B6 (Pyridoxine, PLP)
B7 (Biotin)
B9 (Folate)
B12 (Cobalamin)
C (Ascorbic acid)
B-complex deficiencies usually cause: Dermatitis, Glossitis, & Diarrhea
82
Vitamin A
Includes Retinol, Retinol, & Retinoic acid
Functions:
Antioxidant
Retinal pigment
Differentiate epithelium to specialized tissue
Prevents squamous metaplasia
Deficiency:
Night-Blindness (nyctalopia)
Dry/scaly skin (xerosis cutis)
Dry eyes (xerophthalmia)
Bitot spots (foamy conjunctiva)
Immunosuppression
Excess:
Acute toxicity (nausea, vomiting, high intracranial pressure (vertigo/blurred vision)
Chronic toxicity (alopecia, dry skin, hepatic toxicity/enlargement, arthralgia, idiopathic intracranial hypertension)
83
A 7-year-old girl is brought to a clinic because of fatigue and weight loss. She immigrated from a developing country with her family 1 week ago. The family has had very poor access to food for the past 2 years. The child says she feels itchiness all the time. She is at the 5th percentile for body weight, 50th percentile for height. On examination, her abdomen is scaphoid. She has dry eyes, and further evaluation shows diminished lacrimal gland function.
Vitamin A deficiency
Is associated with night blindness, decreased immunity, and impaired differentiation of specialized epithelia such as that on the eye (causing xerophthalmia and Bitot spots).
84
Mary is a 32-year-old woman who presents with increased flatulence, bloating, and diarrhea while eating a regular diet, including grains, meats, and vegetables. A biopsy shows blunting of intestinal villi. What is the likely cause of her malabsorption?
Celiac disease
Crohn disease
Lactose intolerance
Pancreatic insufficiency
Ulcerative colitis
The correct answer is celiac disease (A). Malabsorption and blunting of intestinal villi are hallmarks of celiac disease, an autoimmune process in response to gliadin, a component of gluten. Crohn's disease (B), lactose intolerance (C), pancreatic insufficiency (D), and ulcerative colitis (E) can present with similar symptoms but don’t have the hallmark blunting of intestinal villi that is seen in celiac disease.
85
Adam is a 4-day-old male infant who was born at home with the help of a midwife. The delivery was uneventful. He now presents to the emergency department with excessive bleeding around the umbilicus that has failed to heal. What vitamin deficiency should be suspected?
Vitamin B9
Vitamin B12
Vitamin C
Vitamin D
Vitamin K
The correct answer is vitamin K (E), which is essential for the γ-carboxylation of clotting factors II, VII, IX, and X. Newborns are given a shot of vitamin K after birth because deficiency is common. Deficiencies of vitamin B9 (A), B12 (B), C (C), and D (D) would not cause increased bleeding times in this infant.
86
James is a 27-year-old man who complains of abdominal pain, bloating, diarrhea, and increased flatulence with the consumption of milk. What stage of the absorptive process is disrupted?
Intraluminal digestion
Lymphatic transport of lipids
Secretion of regulatory substances
Terminal digestion
Transepithelial transport
The correct answer is terminal digestion (D). This patient is lactose intolerant and is deficient in the brush border enzyme lactase. The malabsorption in this case is an inability to digest the sugar lactose found in milk products. Intraluminal digestion (A) is not specific for lactose and wouldn’t cause this process. Lymphatic transport of lipids (B) is still intact in a patient with lactose intolerance, because the disruption is with digestion of sugar. Disrupting the secretion of regulatory substances (C) can be caused by diseases like pancreatic insufficiency or pernicious anemia. This patient’s symptoms coinciding with milk consumption points to a deficiency of lactase, which is found in the brush border and is not a secreted regulatory substance. The transepithelial transport system (E) is still intact for other food products, because the symptoms are only with milk ingestion.
87
A 10-year-old male is brought to the clinic because of chronic diarrhea and increased fatigue. The patient reports that his stools smell foul and float in the commode. He has no blood in his stool. Vital signs are normal. On physical examination, he appears pale and thin. His abdomen is mildly tender to palpation in all four quadrants. Laboratory studies reveal the following:
Hemoglobin: 9.0 g/dL
Mean corpuscular volume: 73 μm3
Platelet count: 212,000/mm3
Leukocyte count: 6,000/mm3
Ferritin: 15 ng/mL
A duodenal biopsy specimen reveals the findings pictured.
A. Ascending weakness
B. Frequent bloody stools
C. Hyperpigmented skin lesions
D. Painful, tender, erythematous nodules on the shins
E. Small clusters of fluid-filled papules and vesicles
E. Small clusters of fluid-filled papules and vesicles
Celiac disease, an autoimmune disorder with intolerance to gluten, presents with foul-smelling diarrhea, steatorrhea, weight loss, fatigue, and abdominal pain.
Celiac disease is associated with dermatitis herpetiformis, a skin disorder with clusters of pruritic, papular, and sometimes bullous lesions that often appear in a symmetric pattern.
88
A 46-year-old woman goes to the physician because of intermittent bloating, abdominal pain, diarrhea, and flatulence. The diarrhea is watery and never oily. The condition is often worse after meals, but sometimes eating presents no problems. The patient has not tried to identify any dietary triggers and follows a normal diet with no restrictions. There is no family history of gastrointestinal problems. Stool studies reveal an osmotic gap of 200 mOsm/kg.
Which of the following conditions is most likely causing this patient’s symptoms?
A. Crohn disease
B. Escherichia coli enteritis
C. Irritable bowel syndrome
D. Lactose intolerance
E. Peptic ulcer disease
D. Lactose intolerance
Physical indicators of lactose intolerance include intermittent postprandial diarrhea, bloating, flatulence, and abdominal pain; an elevated stool osmotic gap essentially confirms the diagnosis.
89
A 42-year-old man comes to the physician with intermittent right-upper-quadrant abdominal pain that occurs most often after meals. The patient’s body mass index is 34 kg/m2.
Which of the following is most likely associated with this patient’s pain?
Acinar cell hypersecretion
Cholecystokinin release
Decreased gastric pH
Excessive gastrin release
Increased indirect bilirubin
Cholecystokinin release
Patients with gallstones present with postprandial pain in the upper right quadrant.
Cholecystokinin stimulates gallbladder contraction and increases pain in patients with gallstones.
90
A 32-year-old woman comes to the clinic because of chronic abdominal pain, steatorrhea, weight loss, fatigue, and joint pain. Upper endoscopy and tissue biopsy of the small intestine are performed, and the results are shown. The physician tells the patient that the condition can be managed through dietary changes.
Which of the following is associated with this patient’s most likely condition?
Acute lymphoblastic leukemia
Colonic polyp
Diverticula
Herpes simplex virus type 1 infection
Selective IgA deficiency
Selective IgA deficiency
Celiac disease commonly presents with abdominal pain, steatorrhea, weight loss, fatigue, and bone and joint pain. Histologic changes typically include intraepithelial lymphocytes, enterocyte damage, and villous blunting, leading to malabsorption.
Celiac disease is associated with IgA deficiency.
91
In a genetically modified mouse, researchers deleted a gene that is only expressed on the plasma membrane of enterocytes. When tested, the mice were found to have elevated high-molecular-weight proteins and complex lipids in their stool.
Which of the following would be deficient as a result of the most likely gene deletion?
Amylase
Chymotrypsinogen
Enterokinase
Lipase
Pepsin
Enterokinase
Enterokinase (enteropeptidase) allows the activation of several digestive enzymes responsible for degrading proteins and complex lipids.
92
A 22-year-old woman comes to the clinic because of increasing shortness of breath, weakness, and fatigue. She has a history of heavy menstrual bleeding. Physical examination reveals hair loss, koilonychia, and pale mucous membranes. Laboratory studies show a hemoglobin concentration of 6 g/dL, a mean corpuscular hemoglobin concentration of 24 Hb/cell, a mean corpuscular volume of 65 fL, and an RBC distribution width of 17%.
What part of the gastrointestinal tract is responsible for absorbing the nutrient in which this patient is most likely deficient?
Duodenum
Gastric body
Gastric fundus
Ileum
Jejunum
Duodenum
Iron-deficiency anemia is characterized by shortness of breath, weakness, fatigue, pale mucous membranes, low mean corpuscular volume, and high RBC distribution due to reduced oxygen delivery to the body.
Iron is predominantly absorbed in the duodenum, and damage to the duodenal enterocytes can lead to malabsorption of iron and iron-deficiency anemia.
93
A 46-year-old woman comes to the clinic for foul-smelling and bulky stools that float on the surface of the toilet water. She has chronic epigastric pain that is worse after eating. Her diarrhea resolves when she abstains from eating. Her medical history is significant for chronic heavy alcohol use. Physical examination reveals temporal wasting and epigastric tenderness. Her fasting serum glucose is 148 mg/dL.
Which of the following additional findings is most likely in this patient?
Blood and pus in the stool
Decreased transit time
Elevated 72-hour fecal fat
Positive Clostridioides difficile polymerase chain reaction
Reduced stool osmotic gap
Elevated 72-hour fecal fat
Chronic pancreatitis commonly manifests as a malabsorptive diarrhea because the pancreas is no longer capable of secreting an adequate amount of amylase and lipase (which are responsible for the digestion of carbohydrates and lipids).
Consequently, fats remain undigested in the intestines, and fecal fat levels are elevated.
94
A 49-year-old man presents to the physician with a 3-month history of joint pain throughout the body. Recently, the patient also has experienced abdominal pain, greasy stools, and a 6-kg (13.2-lb) weight loss. Physical examination is normal. The physician obtains a biopsy specimen of the lamina propria of the small intestine, and the results are shown.
Which of the following is the cause of this man’s symptoms?
Celiac sprue
Crohn disease
Mucosa-associated lymphoid tissue tumour
Ulcerative colitis
Whipple disease
Whipple disease
Caused by infection with T. whipplei, Whipple disease manifests via weight loss, diarrhea, and arthralgias; in addition, histology reveals PAS-positive macrophages in the lamina propria of the small intestine.
95
Vitamin B1
Aka Thiamine (TPP)
Functions:
Cofactor for
- Branched-chain ketoacid dehydrogenase
-A-ketoglutarate dehydrogenase (TCA)
- Pyruvate dehydrogenase (Links glycolysis --> TCA)
- Transketolase (HMP-shunt)
Deficiency:
Impaired glucose breakdown (worse with glucose infusion)
&
Give patients with chronic alcohol abuse or malnutrition. Thiamine before dextrose to avoid Wernicke's encephalopathy!!
Labs:
High RBC transketolase activity from the administration of B1
Chronic toxicity (alopecia, dry skin, hepatic toxicity/enlargement, arthralgia, idiopathic intracranial hypertension)
Conditions:
Wernicke encephalopathy
Korsakoff Syndrome
BeriBeri (wet/dry)
96
Wernicke encephalopathy
"CorONA beer"
Acute & reversible but life-threatening neurological condition
Signs:
Confusion
Ophthalmoplegia
Nystagmus
Ataxia
97
Korsakoff Syndrome
Amnestic disorder from chronic alcohol abuse
Signs:
Confabulation
Personality changes
Permanent memory loss
98
Wernike-Korsakoff syndrome
Damaged medial dorsal nucleus of the thalamus + mamillary bodies
Signs: COMBO
Confusion
Ophthalmoplegia
Nystagmus
Ataxia
Confabulation
Personality changes
Permanent memory loss
99
Wernickes vs Korsakoff "COAT RACK"
100
Wet vs Dry Ber1Ber1
Wet: Polyneuropathy + symmetrical muscular wasting
Dry: High-output cardiac failure (dilated cardiomyopathy) + edema
101
Vitamine B2
"B2= 2ATP"
Riboflavin
Functions:
Part of FAD & FMN as cofactors in redox reactions (succinate DH (TCA))
Deficiency:
Cheilosis
102
Cheilosis
"2 C's of B2"
Vitamin B2 deficiency
Signs:
Inflamed & Scaling/fissured lips
Magenta tongue
Corneal vascularization
103
Vitamin B3
"BC3 =3ATP"
Niacin & Nicotinic acid
Functions:
Derived from Tryptophan (needs Vit B2 + B6 to be made)
Part of NAD/NADP in redox reactions & cofactors for dehydrogenases
Used to treat dyslipidemia
Deficiency:
Glossitis
Pellagra
Causes of deficiency;
Hartnup disease
Excess:
Facial flushing (prostaglandin induced)
Gout (hyperuricemia)
Hyperglycemia
104
Pellagra
3 D's
Can be due to a vitamin B3 deficiency
Dementia
Dermatitis
Diarrhea
105
Hartnup disease
AUTO REC
Deficient in neutral AAs like tryptophan causing vitamin deficiencies like Vit B3 def
Rx High protein diet & B3 supplementation
106
Vitamin B5
Pantothenic acid
Function:
Part of coenzyme A (CoA cofactor for acyl-transferases) & fatty acid synthesis
Deficiency:
Dermatitis
Enteritis
Alopecia
Adrenal insufficiency (burning feet syndrome)
Distal paresthesias
Dysesthesia
107
Vitamin B6
Pyridoxine
Function:
Converted to PLP, a cofactor in transamination (ALT/AST), decarboxylation, & glycogen phosphorylase-type reactions
Synthesis requires;
Glutathione
Cystathionine
Heme
Niacin
Histamine
Neurotransmitters (Serotonin, Epi/NoreEPI, Dopamine, & GABA)
Deficiency:
Convulsions
Hyperirritability
Peripheral neuropathy (Isoniazid inducible (from TB Rx))
Sideroblastic anemia
108
Vitamin B7
Biotin
Function:
Cofactor for carboxylation enzymes
- pyruvate carboxylase (gluconeogenesis, pyruvate --> OAA)
- acetyl-CoA carboxylase(fatty acid synthesis,acetylCoA ->MalonylCoA)
- propionyl CoA carboxylase
(fatty acid oxidation, propionyl CoA->Methylmalonyl-CoA)
Deficiency:
Dermatitis
Enteritis
Alopecia
109
Vitamin B9
"Give vit B9 at 9months preggo"
Folate
Function:
Made into THF (tetrahydrofolic acid)
&
Important for nitrogenous base synthesis in DNA/RNA
Deficiency:
Macrocytic megaloblastic anemia with hypersegmented PMN cells
Glossitis
NO neurological symptoms (as opposed to Vit B12 def)
High homocysteine levels
Normal methylmalonic acid
Causes:
Chronic alcohol abuse
Pregnancy
Drugs (Methotrexate, Phenytoin, & Sulfonamides)
110
Vitamin B12
Cobalamin
Functions:
Cofactor for methionine synthase & methyl malonyl-CoA mutase
Important for DNA synthesis
Deficiency:
Macrocytic megaloblastic anemia with hyper-segmented PMN cells
Paresthesia
NEUROLOGICAL SYMPTOMS
High homocysteine & methylmalonic acid levels
Causes:
Malabsorption
- Alcohol abuse, bacterial overgrowth, prolonged antibiotic use, or diphyllobotherium latum (tapeworm)
Lack of intrinsic factors
- Gastric bypass or pernicious anemia
Absent terminal ileum
Drugs (metformin)
Vegans
111
Vitamin C
Ascorbic acid
Functions:
Antioxidant
Facilitates ferritin absorption by reducing it to iron
Cofactor for hydroxylation of lysine & proline in collagen synthesis
Needed for Dopamine B-hydroxylase to make Norepinephrine
Deficiency:
Scurvy
Causes:
Tea & Toast diet (usually affects elderly)
Excess:
Nausea, vomiting, diarrhea
Fatigue
Calcium oxalate nephrolithiasis
Can worsen hemochromatosis or transfer related iron overloads
112
Scurvy
Vitamin C deficiency
Signs:
Swollen/bleeding gums
Easy bruising
Petechiae
Hemarthrosis
Anemia
Poor wound healing
Perifollicular + subperiosteal hemorrhages
Cork-screw hair
Immuno suppression
113
Vitamin D
D2 (Ergocalciferol) = Sun, fish, milk, & plants
D3 (Cholecalciferol) = Plants, fungi, & yeast
Stored in the liver as 25-OH D3
Activated in the kidney as 1,25-(OH)2 D3
Function:
Intestine Ca2+ absorption
Bone storage/reabsorption of Ca2+ (if serum Ca2+ is high)
Bone mineralization/sequestration of Ca2+ (if serum Ca2+ is low)
Regulation:
PTH
- Increases serum Ca (more intestine absorption, bone mineralization, & PCT reabsorption of Ca2+)
Deficiency:
Rickette (kids)
Osteomyalgia (adults)
114
Ricketts vs Osteomyalgia
Both Vitamin D deficiency
Signs:
Rickettes --> Genu varum (Bow leg)
Osteomyalgia --> Bone pain/weakness
Both hypocalcemic tetany
Cause:
Malabsorption
Little sun exposure
Diet
Chronic liver or kidney disease
Risks:
dark skin & premature birth
115
Vitamin E
Tocopherol, Tocotrienol
Functions:
Antioxidant (protects RBC & cell membranes from free radicals)
Deficiency:
Hemolytic anemia
Acanthocystocis
Muscle weakness
Demyelination (low proprioception + vibration sensation)
Ataxia
Similar neurological deficits to vit B12 deficiency but NO megaloblastic anemia
Excess:
Risk of enterocolitis in infants
High dose of vitamin E fucks with vitamin K synthesis & enhances the anticoagulant effects of Warfarin
116
Vitamin K
"K is for Koagulation"
"breast fed infants Don't Know about vitamins K & D"
Phytomenadione, phylloquinone, phytonadione, & menaquinone
Function:
Activated by epoxide reductase in the liver to be a cofactor for y-carboxylation of glutamic acid residues on clotting proteins (II
, VII, IX, X, C, & S
Deficiency:
Neonatal hemorrhage with high PT & aPTT
117
Zinc
Function:
Is essential for enzymes like transcription factor motifs
Deficiency:
Delayed wound healing
Suppressed immunity
Male hypogonadism
Less adult hair
Dysgensia (tongue)
Anosmia
Associated Conditions:
Acrodermatitis enteropathica (defective zinc absorption in intestines)
Pre-disposed to alcoholic cirrhosis
118
Protein-energy malnutrition:
Kwashiorkor (MEALS)
Marasmus
Kwashiorkor:
Malnutrition
Edema
Anemia
Liver (fatty)
Skin lesions (hyperkeratosis/depigmentation)
Marasmus:
NO edema
Deficient calories
Sufficient nutrients
Muscle wasting
119
Ethanol metabolism
High NADH/NAD ratio from ethanol metabolism:
- Inhibits TCA
- Increases Ketogenesis, ketoacidosis, Hepatosteatosis, & lipogenesis
-Fasting glycemia (inhibited gluconeogenesis cause OOA goes to malate)
-
120
Glycolysis
Rate-determining enzymes
Regulators
RLE:
Phosphofructokinase-1 (PFK-1)
Regulators:
AMP ⊕, fructose-2,6-bisphosphate ⊕
ATP ⊝, citrate ⊝
121
Gluconeogenesis
Rate-determining enzymes
Regulators
RLE:
Fructose-1,6-bisphosphatase 1
Regulators:
AMP ⊝, fructose-2,6-bisphosphate ⊝
TCA cycle Isocitrate dehydrogenase ADP ⊕
ATP ⊝, NADH ⊝
122
Glycogenesis
Rate-determining enzymes
Regulators
RLE:
Glycogen synthase Glucose-6-phosphate ⊕
Regulators:
insulin ⊕, cortisol ⊕
Epinephrine ⊝, glucagon ⊝
123
Glycogenolysis
Rate-determining enzymes
Regulators
RLE:
Glycogen phosphorylase
Regulators:
Epinephrine ⊕, glucagon ⊕, AMP ⊕
Glucose-6-phosphate ⊝, insulin ⊝, ATP ⊝
124
HMP shunt
Rate-determining enzymes
Regulators
RLE:
Glucose-6-phosphate dehydrogenase (G6PD)
Regulators:
NADP+ ⊕
NADPH ⊝
125
De novo pyrimidine
synthesis
Rate-determining enzymes
Regulators
RLE:
Carbamoyl phosphate synthetase II
Regulators:
ATP ⊕, PRPP ⊕
UTP ⊝
126
De novo purine
synthesis
Rate-determining enzymes
Regulators
RLE:
Glutamine-phosphoribosylpyrophosphate
(PRPP) amidotransferase
Regulators:
AMP ⊝, inosine monophosphate (IMP) ⊝,
GMP ⊝
127
Urea cycle
Rate-determining enzymes
Regulators
RLE:
Carbamoyl phosphate synthetase I
Regulator:
N-acetylglutamate ⊕
128
Fatty acid synthesis
Rate-determining enzymes
Regulators
RLE:
Acetyl-CoA carboxylase (ACC)
Regulators:
Insulin ⊕, citrate ⊕
Glucagon ⊝, palmitoyl-CoA ⊝
129
Ketogenesis
Rate-determining enzymes
RLE:
HMG-CoA synthase
130
Cholesterol synthesis
Rate-determining enzymes
Regulators
RLE:
HMG-CoA reductase
Regulators:
Insulin ⊕, thyroxine ⊕, estrogen ⊕
Glucagon ⊝, cholesterol ⊝
131
Metabolism sites:
Mitochondria
Fatty acid oxidation (β-oxidation)
Acetyl-CoA production
TCA cycle, oxidative phosphorylation
Ketogenesis
132
Metabolism sites:
Cytoplasm
Glycolysis
HMP shunt
Synthesis of cholesterol (SER)
Proteins (ribosomes, RER)
Fatty acids and nucleotides.
133
Metabolism sites:
Cytoplasm & Mitochondria
"Hugs take two (both)"
Heme synthesis
Urea cycle
Gluconeogenesis
134
Summary of metabolic pathways
135
Key enzymes in lipid transport:
Cholesteryl ester transfer protein
Hepatic lipase
Hormone-sensitive lipase
Lecithin-cholesterol acyltransferase
Lipoprotein lipase
Pancreatic lipase
PCSK9
Cholesteryl ester transfer protein: Mediates transfer of cholesteryl esters to other lipoprotein particles.
Hepatic lipase Degrades TGs remaining in IDL and chylomicron remnants.
Hormone-sensitive lipase
Degrades TGs stored in adipocytes. Promotes gluconeogenesis by releasing glycerol.
Lecithin-cholesterol acyltransferase
Catalyzes esterification of 2⁄3 of plasma cholesterol (ie, required for HDL maturation).
Lipoprotein lipase Degrades TGs in circulating chylomicrons.
Pancreatic lipase Degrades dietary TGs in small intestine.
PCSK9 Degrades LDL receptor serum LDL. Inhibition LDL receptor recycling serum LDL.
136
MEN 1 (autosomal dominant MEN1 mutation)
MEN 2B (autosomal dominant RET mutation)
MEN 2A (autosomal dominant RET mutation)
Pancreatic, pituitary, parathyroid tumors
Thyroid tumors, pheochromocytoma,
ganglioneuromatosis, Marfanoid habitus
Thyroid and parathyroid tumors, pheochromocytoma
137
Bronze skin
Orthostatic hypotension
Fatigue,
Weakness
Muscle aches
Weight loss
GI disturbances
Chronic 1° adrenal insufficiency (Addison disease) HIGH ACTH & α-MSH
138
Shock, altered mental status, vomiting, abdominal pain,
weakness, fatigue
Acute adrenal insufficiency (adrenal crisis)
139
Metabolic acidosis & compensatory respiration:
Deep, labored breathing/hyperventilation
Diabetic ketoacidosis (Kussmaul respirations)
140
Jaundice, palpable distended non-tender gallbladder
Courvoisier sign (distal malignant obstruction of biliary
tree)
141
Arthralgias, adenopathy, cardiac and neurological
symptoms, diarrhea
Whipple disease (Tropheryma whipplei)
142
Severe jaundice in neonate
Crigler-Najjar syndrome (congenital unconjugated
hyperbilirubinemia)
143
Golden brown rings around peripheral cornea
&
Low serum ceruloplasmin
Wilson disease (Kayser-Fleischer rings due to copper
accumulation
144
Female, fat, fertile, forty
Cholelithiasis (gallstones)
145
Painless jaundice with enlarged gallbladder
Cancer of the pancreatic head obstructing bile duct
146
Bluish line on gingiva
Burton line (lead poisoning)
147
Short stature, café-au-lait spots, thumb/radial defects,
incidence of tumors/leukemia, aplastic anemia
Fanconi anemia (genetic loss of DNA crosslink repair;
often progresses to AML)
148
Sudden swollen/painful big toe joint, tophi
Gout/podagra (hyperuricemia)
149
Swollen, hard, painful finger joints in an elderly
individual, pain worse with activity
Osteoarthritis (osteophytes on PIP [Bouchard nodes], DIP
[Heberden nodes])
150
Bone pain, bone enlargement, arthritis
Osteitis deformans (Paget disease of bone, osteoblastic
and osteoclastic activity)
151
Urethritis, conjunctivitis, arthritis in a male
Reactive arthritis associated with HLA-B27
152
Cervical lymphadenopathy, desquamating rash, coronary
aneurysms, red conjunctivae and tongue, hand-foot
changes
Kawasaki disease (mucocutaneous lymph node syndrome,
treat with IVIG and aspirin)
152
Kawasaki disease (mucocutaneous lymph node syndrome,
treat with IVIG and aspirin)
Cervical lymphadenopathy, desquamating rash, coronary
aneurysms, red conjunctivae and tongue, hand-foot
changes
153
Resting tremor, rigidity, akinesia, postural instability,
shuffling gait, micrographia
&
Depigmentation of neurons in substantia nigra
Parkinson disease (loss of dopaminergic neurons in
substantia nigra pars compacta)
154
Chorea, dementia, caudate degeneration
Huntington disease (autosomal dominant CAG repeat
expansion)
155
Rapidly progressive limb weakness that ascends following
GI/upper respiratory infection
Guillain-Barré syndrome (acute inflammatory
demyelinating polyneuropathy)
156
Renal cell carcinoma (bilateral), hemangioblastomas,
angiomatosis, pheochromocytoma
von Hippel-Lindau disease (deletion of VHL gene on
chromosome 3p)
157
Staggering gait, frequent falls, nystagmus, hammer toes,
diabetes mellitus, hypertrophic cardiomyopathy
Friedreich ataxia
158
Ptosis, miosis, anhidrosis
Horner syndrome (sympathetic chain lesion
159
Polyuria, renal tubular acidosis type II, growth retardation,
electrolyte imbalances, hypophosphatemic rickets
Fanconi syndrome (multiple combined dysfunction of the
proximal convoluted tubule
160
Periorbital and/or peripheral edema, proteinuria (> 3.5g/
day), hypoalbuminemia, hypercholesterolemia
Nephrotic syndrome
161
Hereditary nephritis, sensorineural hearing loss,
retinopathy, lens dislocation
Alport syndrome (mutation in type IV collagen)
162
Beckwith-Wiedemann syndrome (WT2 mutation)
Wilms tumor, macroglossia, organomegaly,
hemihyperplasia, omphalocele
163
Streak ovaries, congenital heart disease, horseshoe kidney,
cystic hygroma, short stature, webbed neck, lymphedema
Turner syndrome (45,XO)
164
Colonies of mucoid Pseudomonas in lungs
Cystic fibrosis (autosomal recessive mutation in CFTR
gene fat-soluble vitamin deficiency and mucous plugs)
165
high AFP in amniotic fluid/maternal serum
Down syndrome, Edwards syndrome
166
high β-hCG, low PAPP-A on first trimester screening
Down syndrome
167
High serum homocysteine, high mehtylmalonic acid, low folate
Vitamin B12 deficiency
168
low T cells, PTH, & Ca2+, absent thymic shadow on CXR
Thymic aplasia (DiGeorge syndrome, velocardiofacial
syndrome)
169
Large granules in phagocytes, immunodeficiency
Chédiak-Higashi disease (congenital failure of
phagolysosome formation)
170
Recurrent infections, eczema, thrombocytopenia
Wiskott-Aldrich syndrome
171
Hypertension, hypokalemia, metabolic alkalosis
1° hyperaldosteronism (eg, Conn syndrome)
172
Anti-transglutaminase/anti-gliadin/anti-endomysial
antibodies
Celiac disease (diarrhea, weight loss
173
Narrowing of bowel lumen on barium x-ray
“String sign” (Crohn disease
174
“Lead pipe” appearance of colon on abdominal imaging
Ulcerative colitis (loss of haustra)
175
Thousands of polyps on colonoscopy
Familial adenomatous polyposis (autosomal dominant,
mutation of APC gene)
176
Eosinophilic cytoplasmic inclusion in liver cell
Mallory body (alcoholic liver disease)
177
Triglyceride accumulation in liver cell vacuoles
Fatty liver disease (alcoholic or metabolic syndrome)
178
“Nutmeg” appearance of li
Chronic passive congestion of liver due to right heart
failure or Budd-Chiari syndrome
179
Hypersegmented neutrophils
Megaloblastic anemia (B12 deficiency: neurologic
symptoms; folate deficiency: no neurologic symptoms)
180
Basophilic nuclear remnants in RBCs
Howell-Jolly bodies (due to splenectomy or nonfunctional
spleen
181
Basophilic stippling of RBCs
sideroblastic anemia
182
Hypochromic, microcytic anemia
Iron deficiency anemia, lead poisoning, thalassemia (fetal
hemoglobin sometimes present
183
“Hair on end” (“crew cut”) appearance on x-ray
β-thalassemia, sickle cell disease (marrow expansion
184
Anti-GpIIb/IIIa antibodies
Immune thrombocytopenia
185
Needle-shaped, ⊝ birefringent crystals
Gout (monosodium urate crystals
186
high uric acid levels
Gout, Lesch-Nyhan syndrome, tumor lysis syndrome,
loop and thiazide diuretics
187
“Bamboo spine” on x-ray
Ankylosing spondylitis (chronic inflammatory arthritis:
HLA-B27)
188
Protein aggregates in neurons from hyperphosphorylation
of tau protein
Neurofibrillary tangles (Alzheimer disease) and Pick
bodies (Pick disease)
189
Silver-staining spherical aggregation of tau proteins in
neurons
Pick bodies (frontotemporal dementia: progressive
dementia, changes in personality)
190
“Waxy” casts with very low urine flow
Chronic end-stage renal disease
191
WBC casts in urine
Acute pyelonephritis, transplant rejection,
tubulointerstitial inflammation
192
RBC casts in urine
Glomerulonephritis
193
hCG elevated
Multiple gestations, hydatidiform moles,
choriocarcinomas, Down syndrome
194
Disease occurs in both males and females, inherited
through females only
Mitochondrial inheritance
195
Down syndrome, fragile X syndrome
Intellectual disability
196
Folate (pregnant women are at high risk; body stores only
3- to 4-month supply; prevents neural tube defects
Vitamin deficiency (USA)
197
Gaucher disease
Lysosomal storage disease
198
Diabetes mellitus type 1, SLE, Graves disease, Hashimoto
thyroiditis (also associated with HLA-DR5), Addison
disease
HLA-DR3
199
Diabetes mellitus type 1, rheumatoid arthritis, Addison
disease
HLA-DR4
200
Renal artery stenosis, chronic kidney disease (eg,
polycystic kidney disease, diabetic nephropathy),
hyperaldosteronism
Hypertension, 2°
201
Marfan syndrome (idiopathic cystic medial degeneration)
Aortic aneurysm, thoracic
202
Pituitary adenoma (usually benign tumor)
Hypopituitarism
203
Thyroid dysgenesis/dyshormonogenesis, iodine deficiency
Congenital hypothyroidism (cretinism)
204
Papillary carcinoma (childhood irradiation)
Thyroid cancer
205
Iatrogenic (from corticosteroid therapy)
Adrenocortical adenoma (secretes excess cortisol)
ACTH-secreting pituitary adenoma (Cushing disease)
Paraneoplastic (due to ACTH secretion by tumors)
Moon face buffalo hump
Cushing syndrome
206
Hypocalcemia of chronic kidney disease
2° hyperparathyroidism
207
Adenomas, hyperplasia, carcinoma
1° hyperparathyroidism
208
Accidental excision during thyroidectomy
Hypoparathyroidism
209
Adrenal hyperplasia or adenoma
1° hyperaldosteronism
210
Zollinger-Ellison syndrome (gastrinoma of duodenum or
pancreas), associated with MEN1
Refractory peptic ulcers and high gastrin levels
211
Cushing ulcer ( intracranial pressure stimulates vagal
gastric H+ secretion)
Acute gastric ulcer associated with CNS injury
212
Gilbert syndrome (benign congenital unconjugated
hyperbilirubinemia
Hereditary harmless jaundice
213
Wilson disease
Hereditary ATP7B mutation (copper buildup in liver,
brain, cornea, kidneys
214
Hemochromatosis
Multiple blood transfusions or hereditary HFE mutation
(can result in heart failure, “bronze diabetes,” and risk
of hepatocellular carcinoma)
215
Pancreatitis (acute
Gallstones, alcohol
216
Pancreatitis (chronic)
Alcohol (adults), cystic fibrosis (kids
217
Iron deficiency
Microcytic anemia
218
Sickle cell disease (hemoglobin S)
Autosplenectomy (fibrosis and shrinkage)
219
Turner syndrome (45,XO or 45,XO/46,XX mosaic)
1° amenorrhea
220
Winters formula
221
Henderson-Hasselbalch equation (for
extracellular pH)
222
Anion gap
223
AUTO REC
Mutated MTP gene
No chylomicrons, VLDL, LDL in blood
Def ApoB100/48
Severe fat malabsorption
Fail to thrive
Retinitis pigmentosa
Vitamin E def
Progressive Ataxia
Acanthocytosis
Abetalipoproteinemia
224
Heat intolerance
Weight loss
Palpitations
Hyperthyroidism
225
Cold intolerance
Weight gain
Brittle hair
Hyperthyroidism
226
AUTO REC
DEF lipoprotein lipase or ApoC
High chylomicrons, TG, & cholesterol in blood
Pancreatitis
Hepatosplenomegaly
eruptive/pruritic xanthomas
I-Hyper chylomicronemia
227
AUTO DOM
Absent/Def LDLR or ApoB100
High IIa: LDL & cholesterol & IIb LDL, Cholesterol, & VLDL in blood
Atherosclerosis
Tendon xanthoma
Corneal arcus
II Hypercholesteremia
228
AUTO REC
Def ApoE
High chylomicrons, VLDL in blood
Premature atherosclerosis
tuberoeruptive/palmar xanthomas
III Dysbetalipoproteinemia
229
AUTO DOM
Too much hepaiv VLDL with high VLDL & TG levels in the blood
Acute pancreatitis
III Hypertriglyceridemia
230
X-linked REC
Peripheral neuropathy
Preg renal failure
Def a-galactosidase
Build up of ceremide trihexoside
Fabry
231
Developmental delay
Corneal clouding
AUTO REC
Hepatosplenomegaly
Def A-L IDURONIDASE
Build up of heparan & dermatan sulfate
Hurlers
232
Aggression
Milder than hurlers
X-linked REC
Def Iduronate 2 sulfatase
Build up of heparan & dermatan sulfate
Hunters
233
No LCFA transport into the mitochondria
Weakness
Hypotonia
Hypoketotic
Hypoglycemia
Dilated cardiomyopathy
Systemic primary carnitine def
234
Accumulation of fatty acyl carnitine in blood
Hypoketotic
Hypolgycemia
Hyperammonia
Vomit
Lethargy
Seizures
Coma
Liver dysfunction
Medium Chain Acetyl-CoA Dehydrogenase def
235
AUTO REC
Hepatomegaly
Foam cells
def sphingomyelinase
build up of sphingomyelin
cherry red spot on macula
Nieman picks
236
Hepatosplenomegaly
Osteoporosis
pancytopenia
Def glucocerebrosidase
Build up of Glucocerebrosidase
AUTO REC
Gaucher
237
AUTO REC
Peripheral neuropathy
Optic atrophy
def Glucocerebroside
Build up of Glucocerebroside
Krabbe
238
Central + peripheral demyelination
Ataxia
Dementia
Def Arylsulfatase A
Build up of cerebroside sulfate
AUTO REC
Metachromatic Leukodystophy
239
Homogentisate oxidase def
Ochronosis (blue/black ears, hands, eyes)
urine turns black when exposed to air
Alkaptonuria
240
Skeletal muscle phosphorylase def
Chronic exercise intolerance
Myalgia/cramps
Myoglobinuria
McArdles
241
Debrancing enzyme def (glu6-phosphatase)
infants with hypoglycemia + hepatomegaly
Cori
242
Lysosomal a 1,4-glucosidase def
Myopathy
Infantile hypertrophic cardiomyopathy
Pompe
243
AUTO REC
Def Hexosaminidase A
Build up of Ganglioside
Cherry red macula spot
Developmental delay
Neurodegen
Lysosomes with onion skin
Tay Sachs
244
Hemorrhagic new born disease with
high PT & aPTT
Vit K def
245
HGPRT def
X-linked RED
Gout
Self-Mutilation
Intellectual disability
Lesh-Nyhan Syndrome
246
AUTO REC
Arachnodactyly
Down/out lens dislocation
Pectus deformity
Homocystinuria
247
CFTR gene defect on X7
Phe deletion
Meconium ileus (neonates)
Recurrent pulmonary infection
Nasal polyps
Pancreatic insufficiency
Infertility
Cystic fibrosis
248
Gs protein activating mutation
Unilateral cafe du lait spots + ragged edges
Polyostotic fibrous displagia (bone replaced by collagen)
McCune-Albright syndrome
249
Def vitamin B1
Dilated cardiomyopathy/high out put cardiac failure
Edema
Alcoholism or malnutrition
Ber1Ber1
250
Burning feet syndrome
Vit B5 def
251
Vit B3 def
pellagra (dermatitis, dementia, diarrha)
252
Catecholamine Met
253
Adrenals & hormones
254
FA MET
255
FEDVSFASTED
256
HH equation
257
ETC
258
Chylomicron transport
259
Anterior pituitary hormone release pathway
260
Calcium reg
261
Cholesterol hormone synthesis enzymes
262
Pituitary hormone pathway
263
Carnitine shuttle
264
Steroid hormone pathways
265
Pyruvate MET
266
Apolipoproteins
267
VLDL
268
Pancreas cells
269
Endocrine hormone signalling pathways
270
Adrenal steroid hormone synthesis pathway
271
G6P path
272
Cholesterol hormone synthesis enzymes
273
ADH
