Vitamins

Front 1

What are the FAT soluble vitamins?

Back 1

ADEK

**Absorption depends on gut (ileum) and pancreas
=malabsorption syndromes (steatorrhea) such as CF and SPRUE or MINERAL OIL INTAKE can cause fat-soluble vitamin deficiencies

**Toxicity MORE COMMON than for water-soluble vitamins--i.e. these accumulate in fat!

Front 2

What are the WATER soluble vitamins?

Back 2

B1 (=thiamine: TPP)
B2 (=riboflavin: FAD, FMN)
B3 (=niacin: NAD+)
B5 (=panthothenate: CoA)
B6 (=pyridoxine: PP)
B12 (=cobalamin)
C (=ascorbic acid)
Biotin
Folate

Front 3

About water soluble:

Back 3

**all wash out easily from the body EXCEPT B12 (=stored in the liver)

**B-complex deficiencies often result in dermatitis, glossitis, and diarrhea.

Front 4

Vitamin A = Function

Back 4

(retinol)

**Found in leafy veggies
=constitutent of visual pigments (retinal)

**Retin-A used topically to treat wrinkles and acne

Front 5

Deficiency

Back 5

night blindness, dry skin

Front 6

Excess

Back 6

=arthralgias
=fatigue
=HA
=skin changes
=alopecia
=sore throat

Front 7

Vitamin B1 Function

Back 7

(thiamine)

**A component of THIAMINE PYROPHOSPHATE = a cofactor for oxidative decarboxylation of alpha ketoacids (=pyruvate, alpha-ketoglutarate)

**Also a cofactor for TRANSKETOLASE in the HMP shunt

Front 8

Deficiency

Back 8

**Beriberi

**Wernicke-Korsakoff Syndrome

=seen in alcholism and malnutrition

Front 9

Dry Beriberi

Back 9

=polyneuritis, muscle wasting

Front 10

Wet Beriberi

Back 10

=high output cardiac failure (dilated cardiomyopathy)

=edema

Front 11

Vitamin B2

Back 11

(riboflavin)

=cofactor in oxidation and reduction (i.e. FADH2 --> FAD and FMN are derived from riboFlavin!)

Front 12

Deficiency

Back 12

=angular stomatitis

=cheilosis

=corneal vascularization

Front 13

Vitamin B3

Back 13

(niacin)

**Constitutent of NAD, NADP
=used in redox reactions

**Derived from TRYPTOPHAN using vitamin B6

Front 14

Deficiency

Back 14

Pellagra

NOW, pellagra can be caued by 3 mechanisms:

1) Hartnup disease
=dec. tryptophan absorption
2) Malignant carcinoid syndrome
=inc. tryptophan metabolism
3) INH
=dec. vitamin B6

Front 15

Sympotoms of Pellagra:

Back 15

**The 3 D's:

1) Diarrhea
2) Dermatitis
3) Dementia

+ beefy glossitis

Front 16

Vitamin B5

Back 16

(pantothenate)

**Constituent of Coa (=cofactor for acyl transfers)

**Component of fatty acid synthase

Front 17

Deficiency:

Back 17

=dermatitis
=enteritis
=alopecia
=adrenal insufficiency

Front 18

B6

Back 18

(pyridoxine)

**Converted to pyridoxal phosphate, a COFACTOR used in:
1) Transamination (ALT, AST)
2) Decarboxylation
3) Heme Synthesis

Front 19

Deficiency

Back 19

=convulsions
=hyperirritability
=peripheral neuropathy

**Deficiency inducible by:
=INH
=oral contraceptives

Front 20

Vitamin B12

Back 20

(cobalamin)

**Cofactor for homocysteine methylation (transfers CH3 groups as methylcobalmin) AND methylmalonyl-CoA handling

Front 21

Where Found?

Back 21

**Found ONLY in animal products.

=stored primarily in the liver--> large reserve pool (years)

Front 22

What usually causes deficiency?

Back 22

1) Malabsorption
=sprue
=enteritis
=diphyllobothrium lactum

2) Lack of intrinsic factor (=pernicious anemia)

3) Absence of a terminal ileum
=Crohn's disease

**Use Schilling's test to detect deficiency

Front 23

Deficiency?

Back 23

=macrocytic, megaloblastic anemia

=neurological symptoms

=glossitis

Front 24

What else is seen in B12 Deficiency?

Back 24

**Abnormal myelin
=possibly due to DECREASED methionine or INCREASED methylmalonic acid (=from metabolism of accumulated methylmalonyl-CoA)

Front 25

Folic Acid Function

Back 25

**Coenzyme (tetrahydrofolate) for 1-carbon transfer

**Involved in methylation reactions

**Impt. for the synthesis of nitrogenous bases in RNA and DNA

Front 26

Found?

Back 26

**Green leaves
=NOT stored long!

**PABA is the folic acid precursor in bacteria
=i.e. SULFA drugs and DAPSONE (antimicrobials) are PABA analogs

**Take folic acid in early preggers to prevent NT defects

Front 27

Deficiency

Back 27

**MOST COMMON deficiency in US

=macrocytic, megaloblastic anemia
=NO neurological symptoms

Front 28

Biotin

Back 28

**Cofactor for carboxylations:

1) Pyruvate --> oxaloacectate
2) AcetylCoA --> malonyl-CoA
3) Proprionyl-CoA --> methylmalonyl-CoA

Front 29

Deficiency?

Back 29

**Caused by antibiotic use OR ingestion of raw eggs

=dermatitis
=enteritis

Front 30

Vitamin C (ascorbic acid)

Back 30

**Necessary for hydroxylation of proline and lysine in collagen synthesis
=vitamin C CROSSLINKS collagen

**Facilitates iron absorption by keeping iron in Fe2+ reduced state

**Necessary as a cofactor for dopamine --> NE

Front 31

Deficiency

Back 31

**SCURVY:
=swollen gums
=bruising
=anemia
=poor wound healing

Front 32

Vitamin D FORMS

Back 32

D2 = ergocalciferol; consumed in milk

D3 = cholecalciferol; formed in sun-exposed skin

25-OH D3 = storage form

1,25 (OH2) D3 = active form

Front 33

Function:

Back 33

=increased intestinal absorption of calcium and phosphate

Front 34

Deficiency:

Back 34

1) Rickets in kiddos (=bending bones)

2) Osteomalacia in adults (=soft bones)

3) Hypocalcemic tetany

Front 35

Excess:

Back 35

**Hypercalcemia
=loss of appetitie
=stupor

**Seen in SARCOIDOSIS
=epitheliod macrohpages convert vitamin D to its active form

Front 36

Vitamin E

Back 36

**ANTIOXIDANT
=protects erythrocytes from hemolysis

Vitamin E = Erythrocytes

Front 37

Deficiency:

Back 37

**Increased fragility of erythrocytes, neurodysfunction

Front 38

Vitamin K

Back 38

**Catylzes the gamma-carboxylation of glutamic acid residues on the vitamin K-dependent factors: 2, 7, 9, 10, protein C and S

recall: WARFARIN is a vitamin K antagonist!

**Synthesized by intestinal floria
=THERFORE, deficiency can occur after broad-spectrum antibiotics

Front 39

Deficiency

Back 39

**Neonatal Hemorrhage
=increased PT and aPTT but NORMAL bleeding time
=i.e. neonates have sterile intestines --> can't synthesize vitamin K

Front 40

Zinc Deficiency

Back 40

**Delayed wound healing

**Hypogonadism
=decreased adult hair (axillary, facial, pubic)

**MAY predispose to alcoholic cirrhosis

Front 41

Ethanol Metabolism

Back 41

**NAD+ is the limiting reagent

**Alcohol dehydrogenase operates via ZERO-ORDER kinetics

Front 42

What can inhibit acectaldehyde dehydrogenase?

Back 42

=Disulfiram (Antabuse)

THUS, acetaldehyde accumulates --> hangover symptoms

Front 43

Ethanol Hypoglycemia

Back 43

**Ethanol metabolism INCRASES NADH/NAD+ ratio in the liver
=causes diversion of pyruvate --> lactate and OAA --> malate
=this INHIBITS gluconeogenesis and leads to hypoglycemia

**This same altered HADH/NAD+ ratio is responsible for the FATTY CHANGE (hepatocellular steatosis) seen in chronicc alcoholics!
=shunting AWAY from glycolysis and toward fatty acid synthesis!

Front 44

Kwashiokor

Back 44

**PROTEIN malnutrition

=skin lesions
=edema
=liver malfunction (fatty change)

**Clinical picture is a small child with a SWOLLEN belly

Kwashiorkor results from a protein-deficient MEAL = malabsorption, edema, anemia, liver (fatty)

Front 45

Marasmus

Back 45

**Energy (total calorie) malnutrition resulting in:

=tissue and muscle wasting
=loss of subcutaneous fat
=variable edema

Front 46

Autosomal Dominant Diseases

Back 46

1) APKD
2) Familial Hypercholestrolemia
3) Marfan's Syndrome
4) Neurofibromatosis
5) Tuberous Sclerosis
6) Von Hippel-Lindau
7) Huntington's
8) Familial Adenomatous Polyposis
9) Hereditary Spherocytosis
10) Achondroplasia

Front 47

Adult Polycystic Kidney Disease

Back 47

**Always BILATERAL
=massive enlargement of kidneys because of large cysts

**Due to mutation in APKD1 (=chromosome 16)

**Note: Juvenille form is recessive

Front 48

Presentation:

Back 48

=pain
=hematuria
=HTN
=progressive renal failure

**Associated with: polycystic liver disease, berry aneurysms, mitral valve prolapse, sigmoid diverticulosis

Front 49

Familial hypercholestrolemia

Back 49

(Hyperlipidemia Type IIa)

**Elevated LDL because of DEFECTIVE or ABSENT LDL receptor

=Heterozygotes have cholesterol ~ 300
=Homozygotes have cholesterol ~ 700+

Front 50

Presentation:

Back 50

**Severe atherosclerotic disease in early life

**Tendon xanthomas (=Achille's tendon)

**MI may develop before age 20

Front 51

Marfan's Syndrome

Back 51

**Fibrillin gene mutation --> CT disorders

Front 52

Presentation:

Back 52

1) Skeletal abnormalities
=tall with long extremities (arachnodactyly)
=pectus excavatum
=hyperextensive joints
=long, tapering fingers and toes

2) CV
=cystic medial necrosis of the aorta --> aortic incompetance and dissecting aortic aneurysms
=mitral valve prolapse

3) Subluxation of lenses

Front 53

Neurofibromatosis Type I

=von Recklinhausen's Disease

Back 53

**Defect on chromosome 17
=cafe-au-lait spots
=neural tumors
=lisch nodules (pigmented iris hamartomas)

Also: scoliosis, optic pathway gliomas, pheochromycytoma

Front 54

Neurofibromatosis Type II

Back 54

**Bilateral acoustic neuroma

**Juvenille cataracts

NF2 gene on chromosome 22

Front 55

Tuberous Sclerosis

Back 55

**Incomplete penetrance
=variable presentation

=facial lesions, seizures, mental retardation
=hypopigmented "ash leaf patches" on skin
=cortical and retinal hamartomas + renal cysts
=cardiac rhabdomyomas

Front 56

Von-Hippel-Lindau Disease

Back 56

**Associated w/ deletion of VHL gene
=tumor suppressor on chromosome 3p

**See hemangioblastomas of the retina/cerebellum/medulla
=1/2 individuals go on to develop BILATERAL RENAL CELL CARCINOMA

Front 57

Huntington's Disease

Back 57

**Triplet repeat disorder (CAG) on chromosome 4
=decreased levels of Ach and GABA in the brain --> caudate atrophy

=depression, progressive dementia, choreiform movements

Front 58

Familial Adenomatous Polyposis

Back 58

**Deletion on chromosome 5
=colon becomes covered w/ adenomatous polyps after puberty

**Progresses to colon cancer uncless resected

Front 59

Hereditary Spherocytosis

Back 59

=spheroid erythrocytes

=hemolytic anemia, increased MCHC

**Splenectomy curative

Front 60

Achondroplasia

Back 60

**AD cell-signaling defect of FIBROBLAST GROWTH FACTOR (FGF) receptor 3

=dwarfism, short limbs BUT head and trunk are normal in size

**Associated w/ advanced PATERNAL age

Front 61

AR Disorders

Back 61

=CF, albinism, alpha-1-antitrypsin deficiency, PKU, thalassemias, sickle cell, glycogen storage diseases, mucopolysaccharidoses (except Hunters), sphingolipidoses (except Fabrys), infant polycystic kidney disease, hemochromotosis

Front 62

Cystic Fibrosis

Back 62

AR defect in CFTR gene on chromosome 7
=commonly a deletion of Phe508

**Normally, the CFTR channel secretes Cl- in the lungs and GI tract andd reabsorbs Cl from seat

Front 63

SO, what will a defective Cl-Channel Cause?

Back 63

**Secretion of abnormally THICK mucus that PLUGS the lungs, pancreas, and liver
--> recurrent pulmonary infections, chronic bronchitis, bronchiectasis, pancreatic insufficiency (malaborption and steatorrhea), + meconium ileus in newborns

Front 64

What pathogens are CF patients particularly susceptible to?

Back 64

PSEUDOMONAS

+ staph aureus

Front 65

Diagnosis?

Back 65

**Increased concentration of Cl- ions in SWEAT TEST

(most common lethal genetic disease of Caucasians)

Front 66

Treatment:

Back 66

N-acetylcysteine to loosen mucous plugs

Front 67

X-Linked Recessive Disorders

Back 67

**Be Wise, Fool's GOLD Heeds False Hope**

Bruton's agammaglobulinemia, Wiskott-Aldrich Syndrome, Fragile X, G6PD, Ocular albinism, Lesch-Nyhan syndrome, DMD, Hemophilia A and B, Fabry's Disease, Hunters Syndrome

**Female Carriers are RARELY affected --> random inactivation of X chromosomes in each cell

Front 68

Fragile X Syndrome

Back 68

**X-linked defect affeecting the methylation and expression of the FMR1 gene
=chromosome will BREAK when exposed to a folate-depleting substance--i.e. methotrexate--BREAKS at triplet repeats (CGG)

**NOTE that this repeat will show ANTICIPATION

Front 69

Presentation:

Back 69

**2nd most common cause of genetic mental retardation
=AFTER DS

=macro-orchidism, long face w/ a large jaw, large everted ears, autism

Front 70

What are the other trinucleotide repeat diseases?

Back 70

**Huntington's, myotonic dystrophy, fragile X, friedreich's ataxia

**May show anticipation (=disease severity INCRASES and age of onset DECREASES in sucessive generations)

Front 71

Autosomal Trisomies

Back 71

1) DS (Drinking age--21)
2) Edwards Syndrome (Election age--18)
3) Patau's Syndrome (Puberty--13)

Front 72

Down Syndrome

Back 72

Trisomy 21
=1:700
=Most COMMON chromosomal disorder and cause of congenital MR

Front 73

Findings:

Back 73

=mental retardation
=flat facial profile, prominent epicanthal folds, simian crease
=duodenal atresia
=congenital heart disease
=AD (>35)
=increased risk of ALL

Front 74

Most common heart malformation

Back 74

**Septum primum
=ASD due to endocardial cushion defects

Front 75

Genetics--MOST common cause:

Back 75

**95% of cases due to meiotic NONDISJUNCTION of homologous chromosomes
=associated w/ advancced maternal age
=1:1500 women <20
=1:25 in women >45

Front 76

Other causes:

Back 76

**4% due to Robertsonian Translocation

**1% due to Down Mosaicism
=NO maternal association

Front 77

Edwards' Syndrome--Genetics:

Back 77

**Trisomy 18

1:8000

**Death usually within 1 year of birth

Front 78

Findings:

Back 78

=severe mental retardation
=rocker bottom feet
=low-set ears + prominent occiput
=micrognathia (small jaw)
=clenched hands
=congenital heart didsease

Front 79

Patau's Syndrome--Genetics:

Back 79

**Trisomy 13

1:15,000

**Death usually w/i 1 year of birth

Front 80

Findings:

Back 80

=Severe MR
=Micropthalmia and microcephaly
=CLEFT LIP/PALATE
=abornal forebrain structures
=POLYDACTYLY
=congenital heart disease

Front 81

Cri-du-chat Syndrome

Back 81

**Cry of the cat**

=Congential DELETION of the short arm of chromosome 5
(46XX or XY, 5p-)

Front 82

Findings:

Back 82

=microcephaly
=severe MR
=HIGH PITCHED crying/mewing
=epicanthal folds
=cardiac abnormalities

Front 83

22q11 Syndromes

Back 83

CATCH-22 --> microdeletion at 22q11

=cleft palate
=abnormal facies
=thymic aplasia (T-cell deficiency)
=cardiac defects
=hypocalcemia secondary to parathyroid aplasia

Front 84

SO, how can this present?

Back 84

**Variable**

1) DiGeorge Syndrome
=thymic, parathyroid, and cardiac defects

2) Velocardiofacial Syndrome
=palate, facial, and cardiac defects

Front 85

Fetal Alcohol Syndrome

Back 85

**Newborns of mothers who consumed SIGNIFICANT amounts of alcohol (teratogen) during pregnancy
=highest risk at 3-8 weeks
=inhibits CELL MIGRATION

#1 cause of congenital malformations in the US

Front 86

Presentation:

Back 86

=microcephaly, MR
=facial abnormalities
=limb dislocation
=heart and lung fistulas