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157 Cards in this Set

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Codominance
Neither of the two alleles is dominant (eg blood groups)
Variable expression
Nature and severity of the phenotype varies from 1 individual to another
Incomplete penetrance?
Not all individuals with a mutant genotype show the mutant phenotype
Pleotropy?
1 gene has > 1 effect on an individual's phenotype
Imprinting
Differences in phenotype depend on whether the mutation is of maternal or paternal origin.

At a single locus, only one allele is active; the other is inactive (imprinted/inactivated by methylation) --> deletion of the active allele = disease

(eg AngelMan's syndrome: Maternal allele is deleted; Prader-Willi syndrome: Paternal)
Anticipation
Severity of disease worsens or age of onset of disease is earlier in succedding generations (eg Huntingtons dz)
Loss of heterogenitcity
if a pt inherts or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops.
This is not true of oncogenes.
Dominant negative mutation
Exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning
Linkage disequilibrium
Tendency for certain alleles at two linked loci to occur together more often than expected by chance.

Measured in a population, not in a family, and often varies in different populations.
Mosaicism
Occurs when cells in the body have different genetic makeup (eg lyonization-random x inactivation in females)
Loss of heterogenicity
Mutations at different loci can produce the same phenotype (eg albinism)
What are the characteristics of a child with Prader-Willi?
Mental retardation, obesity, hypogonadism, hypotonia
What are the characteristics of a child with Angelmann's syndrome?
Mental retardation, seizures, ataxia, inappropriate laughter (happy puppet)
Four things assumed in Hardy-Weinberg population genetics?
Hardy-Weinberg:
1. there is no mutation occuring at the locus
2. there is no selection for any of the genotypes at the locus
3. mating is completely random
4. there is no migration into or out of the population being considered.
Equations for disease prevalence?
p and q are separate alleles and 2pq = heterozygous prevalence

p^2 + 2pq + q^2 = 1
p + q = 1
HY

Four major clinical findings in Anorexia Nervosa?
1. secondary amenorrhea: loss of body fat --> reduces GnRH secretion --> low FSH/LH --> low estrogen levels --> no menses

2. osteoporosis (HY): from lack of estrogen

3. increased lanugo hair on face (USMLE: this is not androgen-dependant hair)

4. ventricular arrhythmias: MC cause of death
Four lab findings in a pt with anorexia nervosa:
increased cortisol
increased ACTH
increased GH
decreased FSH/LH
Bullimia nervosa is most common in who?
young women
Four complications of bullimia nervosa?
1. acid injury to tooth enamel: brown discoloration due to loss of enamel and exposure of dentine

2. salivary gland enlargement
3. Mallory-Weiss syndrome: laceration of esophageal/stomach mucosa
4. Boerhaave's syndrome: rupture of stomach/distal esophagus (air and secretion get into the pleural cavity = Hammonds crunch - air under mediastinum)
4. electrolyte disturbances: hypokalemic metabolic alkalosis
FA HY:

Full term neonate of uneventful delivery becomes mentally retarded and hyperactive and has a musty odor? Dx?
PKU
Stressed executive comes home from work, consumes 7 martinits in rapid succession before dinner, and becomes hypoglycemic. Mechanism?
NADH increase prevents gluconeogenesis by shunting pyruvate and oxaloacetate to lactate and malate.
Two year old girl has an increase in abdominal girth, failure to thrive, and skin and hair depigmentation: Dx?
Kwashiorkor
Alcoholic develops a rash, diarrhea, and altered mental status: What is the vitamin deficiency?
Vitamin B3 (pellegra)
51yo man has black spots in his sclera and has noted that his urine turns black upon standing.
Dx?
Alkaptouria
25yo man complains of severe chest pain and has xanthomas of his Achilles tendons?
Familial hypercholesterolemia
LDL receptor
A woman complains of intense muscle cramps and darkened urine after exercise: Dx?
McArdle's disease
Two parents with albinism has a son who is normal.

Why is the son not affected?
Locus heterogenicity (mutations at different loci can produce the same phenotype)
How can metabolic alkalosis of a bullemic lead to heart failure?
Met alkalosis --> resp compensation is acidosis (hypoventilation --> keep CO2 in to bind up and make bicarb) --> this is a decrease in oxygen --> hypoxia is bad for heart --> PVC --> R on T --> V-fib --> death.
A 40 yo man has chronic pancreatitis with pancreatic insufficiency: what vitamins are likely deficient?
Vit A, D, E, K
What is the formula for BMI?
weight/(height^2)
What are the increased CA risks in obese people? (3)
colorectal
pancreatic
gallbladder
What musculoskeletal problem are obese people predisposed to?
osteoarthritis
What is the number 1 treatment for an obese patient?
behavior modification
What is the major problem in Kwashiorkor?
Decreased protein intake (calories are fine)
What are 5 signs of Kwashiorkor?
Results from protein deficient Red MEALS:
1. red hair (copper def)
2. Malabsorption
3. Edema
4. Anemia
5. Liver (fatty)
6. Skin lesions (flaky paint dermatitis)
What are the three main features of Marasmus?
1. loss of muscle mass
2. broomstick extremities
3. growth failure
4. loss of subcutaneous fat
What vitamin supplements are needed in patients with cystic fibrosis?
All fat soluble ones (DEAK)

Pancreatic malabsorption of fat and fat soluble vitamins
What vitamin is a:
1. reducing agent (1)
2. cofactor in oxidative decarboxylation (remove CO2) (2)
3. involved in oxidative phosphorylation (2)
1. reducing: Vitamin C
2. remove CO2: thiamine, pyridoxine
3. oxidative phos: riboflavin, niacin
What vitamin serves to add a CO2 (carboxylase)?
Biotin
What vitamin is involved in transaminations?
Pyridoxine
What vitamin is a component of coenzyme A?
Pantothenic acid (B5)
What two vitamins are involved in DNA synthesis?
folate
B12
What three vitamins are involved in cell growth/differentiation?
Vitamin A
Folate
B12
Three vitamins that are antioxidants?
beta carotene, vit E, ascorbic acid (vitamin C)
What three vitamins are needed in hemostasis?
Vit C, K, E
How does Vitamin A work?
Vit A: makes retinal pigments by binding with beta carotine from the diet. It taken up in the SI as retinol esters (chylomicrons) and stored in the liver bound to retinol binding proteins. When visual pigments are needed retinol esters-RBP are released to enter rods and cones of the retina and activates gene transcription to make visual pigments --> maintains rhodopsin in rods for night vision.

Vit A also prevents squamous metaplasia. And aides in bone growth.
Where is vitamin A found?
Leafy vegatables
Deficiency of vit A:
night blindness
squamous metaplasia of corneal epithelium
corneal softening
growth retardation (decreased epiphyseal bone formation)
poor wound healing
One cause of vit A toxicity?
Eating bear liver
Excess of Vit A
Increased intracranial pressure (MC complication) that causes papilledema (USMLE picture)
Convulsions
Liver tox (elevated transaminases)
skin changes
sore throat
alopecia
DDx of papilledema?
Malignant HTN
Space occupying lesion in brain
Pb poisoning
Excess Vit A
What can cause hyper-beta-carotenemia?

What is the toxicity?

Signs? USMLE
B-carotene:
Drinking too much carrot juice

Tox: no tox --> toxicity is due to increased intake of retinoic acid

Signs: white sclera but yellow skin
What is the most important source of Vit D?
sunlight
USMLE:
Is there Vitamin D on colostrum in milk?
NO!
What vitamin is used to treat acute promyelocytic leukemia (M3)??
trans-retinoic acid --> induces maturation of leukemic cells
Causes of Vit D deficiency?
Chronic renal failure (MCC: diabetes)
Q: Pt on phenytonin and has hypocalcemia? Cause?
Phenytoin causes a use-dependant blockade of Na channels; inhibition of glutamate release from excitatory presynaptic neurons. Used in tonic-clonic seizures and a class IB antiarrhy.

Phenytoin induces p450 causing smooth ER metaplasia (increase gamma glutamyl transferase) and decrease Vit D as will as anyother drug.
Q: Pt on phenytoin and OC's -- she got pregnant.
Phenytoin induces p450

Phenytoin causes a use-dependant blockade of Na channels; inhibition of glutamate release from excitatory presynaptic neurons. Used in tonic-clonic seizures and a class IB antiarrhy.
Findings in Rickets bone problems in children vs. Osteomalasia in adults?
Rickets: abnormal calcification of osteoid at the bone/osteoid interface; widening of osteoid seams in the epiphysis of the ribes (rachitic rosary); craniotabes

Adults: defective mineralization of the diaphysis
Describe the differing uses of looking at Vitamin D deficiency using
1. 25 (OH)-D3
2. 1, 25 (OH) D3
1. 25: best evaluates Vit D status due to long circulating 1/2 life and represents non-renal generated Vit D from diet

2. 1, 25 (OH): limited use, use to differentiate between kidney problems (increased in receptor prob, decreased in enzyme deficiency)
Two major differences in Vit D def of renal and nonrenal origin:
Non-renal: low serum phos, low serum 25 (OH)D3, (low serum 1, 25)

Renal: high serum phos, normal serum 25 OH (low 1, 25)
Function of Vitamin E
maintains cell membranes, protecting them from phopholipase A and can neutralize oxidized LDL (so its cardioprotective by decreasing macros with LDL = decrease in foam cells

FA: Vitamin E is for Erythrocytes
What vitamin can help digest atherosclerotic plaques?
Vitamin E
What causes Vit E deficiency?
chronic fat malabsorption (CF MCC)
What are signs of Vit E deficiency?
hemolytic anemia (increased fragility of RBC)

neurodysfunction such as:
spinocerebellar ataxia
posteior column disease
peripheral neuropathy
USMLE:
Man post recovery myocardial infarction is on warfarin and hemorrhages from GI tract. What over the counter supplement could he have been taking?
Vitamin E: an antioxidant that that helps warfarin by blocking gamma carboxylation of Vit K dependant factors.
HY

Most of our vitamin K comes from?
Most vitamin K starts as K1 is converted by colonic bacteria to less active K2. Our body has to convert it to K1 by epoxide reductase (what warfarin blocks) for it to function.
HY

Why do neonates all have Vit K def?
Because their intestines are sterile and unable to synthesize the vitamin K
HY

How does Vitamin K function in clotting?
Vit K catalysizes gamma carboxylation of glutamic acid residues on various proteins concerned with blood clotting.
Serving as a cofactor for factors 2, 7, 9, 10, and protein C and S
HY

What is the best test for Vit K deficiency?
PT (covers all Vit K dependant factors except IX)
What two drugs inhibit Vit K production?
Warfarin and rat poison
How do you treat a child who ate rat poison?
With Vitamin K
Why is heparin given at the same time as warfarin?
Heparin (catalyzes activation of antithrombin III causing decreased thrombin and Xa) so it will take care of stopping already made clotting factors while Warfarin prevents the synthesis of new factors.
Who gets hemorrhagic skin necrosis?
Patients with a Factor C and S deficiency (heterozygous) so they only have 50% of factor levels.
These factors act kind of like Heparin by inhibiting 5a so Thrombin can't be activated.

In these pt after 6hrs of giving Warfarin (prevents formation of new Factor C and S as well as 2, 7, 9, 10) all the factors are depleted --> leads to vessel thrombosis in skin.
Which has more Vit K, breast milk or cows milk?
Cows milk
Deficiency of Vit C:
Scurvy (abnormal osteoid)
swollen gums
bruising
anemia
poor wound healing
USMLE: perifollicular hemorrhage

FA: vit C = Cross links Collagen
Most common cause of Vit C deficiency?
Malnutrition: elderly, alcoholic, smoking (lowers Vit C)
What can be used as an over the counter treatment for methemoglobinemia?
Vitamin C --> reduce iron to ferrous (Fe2+)
Signs of Vit C excess
(don't really understand but many were USMLE)
1. false negative urine dipstick reactions to blood, glucose, bilirubin, nitrites, and leukocyte esterase
2. diarrhea
3. calcium oxalate/uric acid renal stones
Which vitamins are more toxic, water or fat?
Fat soluble - they just get stored there
What are the general functions of thiamine (B1)?
All things dehydrogenase:

pyruvate dehydrogenase complex
alpha ketoglutarate dehydrogenase rxn
alpha ketoglutarate dehydrogenase complex

and cofactor in RBC PPP for transketolase.
Why is a thiamine (B1) def so bad?
It is needed to generate ATP (without you only get 6 of the 36 ATPs from one glucose)
MCC of thiamine def?

Where does thiamine in the diet come from?
Alcoholism

Sources: meat and wheat
Compare wet and dry beriberi of thiamine deficiency:
B1: Ber1-Ber1

Wet: congestive cardiomyopathy (high output heart failure), goes from left to right heart failure (left takes more energy) and right heart failure causes an increase in hydrostatic pressure behind heart = edema.

Dry berberi: demelination syndromes (no ATP to make myelin), peripheral neuropathy (wrist drop), Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia, nystagmus) and Korsakoff's psychosis (inability to remember new/old information)
USMLE:
Pt in ER presents in a semicomatose state. What three things must be given?
Maloxone
IV glucose
IV thiamine
What happens if you give a semicomatose iv glucose but not iv thiamine?
They could develop Wernickes encephalopathy because all the glucose will be converted to pyruvate and all the pyruvate to acetyl CoA (using thiamine) and this will use up all the remaining thiamine and cause acute thiamine deficiency
What reactions does Riboflavin (B2) act in?
Any reactions involving FAD (Succinate to Fumarate)
and
Forms a part of the glutathione reductase in the PPP: produces reduced glutathione, a potent antioxidant.
Three signs of riboflavin (B2) deficiency?
1. MC: Corneal neovascularization
2. Cheilosis
3. Angular stomatitis
(2C's)
What reactions is niacin used?
Niacin (B3)
Any NAD, NADP reaction
What is niacin synthesized from?
Tryptophan (essential aminoacid)
Signs and symptoms of niacin deficiency (B3)?
Pellagra: Diarrhea, Dermatitis (increased skin pigmentation), Dementia (also beefy glossitis)
How is Niacin made?
It is derived from trytophan using vitamin B6
What reaction types does Vitamin B6 (pyrodoxine) mediate?
transaminase rxns
What is the most common cause of pyroxidine deficiency?
Isoniazid therapy for TB
2nd: OC's
What are the sign/symptoms of pyroxidine deficiency?
Sideroblastic anemia with ringed sideroblasts
Peripheral neuropathy
Hyperirritability
Convulsions (esp in infants)
What is the function of Pantothenate (Vit B5)?
It is a constituent of CoA and component of fatty acid synthase.

Pantothen-A is in CoA
What does a deficiency of Vit B5 cause?
Dermatitis
Enteritis
Alopecia
Adrenal insufficiency
HY

What does Biotin do?
Biotin:
Is a cofactor of carboxylations:
1. pyruvate --> OOA
2. Acetyl CoA --> malonyl Co-A
3. Proprionyl CoA --> methylmalonyl CoA
HY:

USMLE: what is a cause of biotin deficiency?
Eating raw eggs
(Avidin in raw egg whites prevents its absorption in the small bowel)

FA: AVIDin in egg whites AVIDly binds biotin
HY:

What is a sign of biotin deficiency?
Alopecia
What are five causes of Vit B12 deficiency?
1. MalAb from celiac sprue
2. enteritis
3. Diphyllobothrium latum mal ab
4. lack of intrinsic factor
5. absence of terminal ileum (Crohn's dz)
Where is B12 primarily stored?
In the liver (storage reserve for years)
What is the folic acid precursor in bacteria and how is this related clinically?
PABA is the folate precursor

Sulfa drugs and dapsone (antimicrobials) are PABA analogs.
Goljan HY

women who is a pure vegan and is breast feeding her baby and the baby develops anemia: Dx?
Vitamin B12 def
Goljan HY

What is the dx of a Schillings test if correct with IF?
Pernicious anemia
Goljan HY

Drug causing a macrocytic anemia in a patient with severe rheumatoid arthritis?
Methotrexate (blocks dihydrofolate reductase)
Goljan HY

What drug is a young women taking if she develops hypertension and a macrocytic anemia?
Birth control pills --> estrogen increases angiotensinogen and blocks reabsorption of monogluatamate
Anemia in an infant that develops when switched from cow's milk to goat's milk?
Goat's milk is low in folate, B6, and iron

And high in K, Cl, arachidonic acid, and linoleic acid when compared to cows milk
Prevention of macrocytic anemia in patients on methotrexate?
Leucovorin rescue -- replenishes N5,10 methylene THF (needed for thymidylate synthesis)
Trace elements

What is the function of chromium?
Helps insulin (great for a type II diabetic to take)
Trace elements

What is copper bound to?
Ceruloplasmin
Trace elements

What does copper do for collagen synthesis?
Copper is a cofactor in lysyl oxidase which cross-links collagen to increase tensile strength
Trace elements

major finding in copper deficiency?
Poor wound healing and weak blood vessels (could potentiate a dissecting aorta)
Trace elements

What is selenium?
A cofactor to glutathione peroxidase that reduces H2O2. Also converts T4 to T3

It serves to stimulate the immune system
Trace elements-HY HY

Nine functions of ZINC
CoF = cofactor

1. Cof for carbonic anhydrase: bicarb reclamation in kidney
2. cof for superoxide dismutase: neutralizes superoxide free radicals
3. cof for alk phos: bone mineralization
4. cof for collagenases: REPLACES TYPE III COLLAGEN WITH TYPE I
5. cof for alcohol dehydrogenase: ethanol met
6. role in macrophage function
7. role in nucleic acid/protein synth
8. role in spermatogenesis
9. role in normal growth
Trace elements-HY HY

What element deficiency may predispose to alcholic cirrhosis?
Zinc, is a cofactor for alcohol dehydrogenase
Trace elements-HY HY

SIX SIGNS OF ZINC DEF?
1. dysgeusia: decreased taste sensation (USMLE) and anosmia
2. poor wound healing (USMLE)
3. rash around the eyes/mouth (USMLE)
4. growth retardation
5. hypogonadism
6. decreased adult hair (axillary, facial, public)
What is the function of soluble fiber?
Lowers serum cholesterol (decreased lipcolic acid)

Sucks up water (and other bad things) from the gut

Increases defecation (less liponic acid hits the GI tract): keeps stool at a low pH, keeping bile acids protonated --> enhance elimination.

Hypoglycemic effect: improves carbohydrate metabolism in diabetes
What health benefit does fiber have?
Fiber decreases risk of colorectal, endometrial, ovarian, prostate, and breast CA

(estrogens are naturally recycled back into body after being put in stool --> fiber keeps estrogen in stool)
HY HY HY

FIVE NORMAL CHANGES WITH AGING?
1. decrease in body weight
2. loss in skeletal muscle
3. relative increase in fat
4. decline in energy requirements
5. slight decline in basal calorie expenditure
HY HY HY

With aging what three variables contribute to dietary problems?
1. drugs interacting with nutrients (cholestyramine, phytates in diet)
2. reduced renal function (decrease in glomerular filtration rate)
3. malabsorption of nutrients (problems with reduced gastric acidity)
HY HY HY

What three dietary inadequacies commonly occur with aging?
Pyridoxine (B6)
Calcium/Vit D
folate
HY HY HY

What two supplements are NOT recommended in elderly?
Iron: lack of menses eliminates need for iron supplements; iron produces free radicals

Vit A: livers ability to clear retinoic acid from blood is reduced; danger of hypervitaminosis A
HY HY HY

What is the purpose of a protein-restricted diets?
Restrict in chronic renal/liver disease

Purpose: reduce the formation of urea and ammonia
USMLE

Three prenatal vitamins:
1. iron
2. folate
3. B12 (only if mom is vegan)
Molecular

Describe the structure of chromatin:
Chromatin: (-) charged DNA loops twice around nucleosome core (core made of 2 each of the + charged H2A, H2B, H3, and H4) to form nucleosome bead.

H1 histone ties the nucleosomes together in a string (30nm fiber)
Molecular

What histone is the only that is not in the nucleosome core?
H1
Molecular

What is heterochromatin? Euchromatin?
Hetero: condensed, transcriptionally inactive; only found in eukaryotes

Euchromatin: found in both prokaryotes and eukaryotes; less condensed and transcrptionally active
Molecular

What is the nucleosome core comprised of?
H2A, H2B, H3 and H4 (these are all postively charged and there are two of each)
Molecular

How many rings do purines have?
Pyrimidines?
Purines: (A,G) 2 rings
2 PURe As Gold

Pyrimidines: C,T,U 1 ring
CUT 1 PY
Molecular

In what way are guanine and thymine unique?

How is uracil made?
Guanine: has a ketone

Thymine: has a methyl

Uracil: formed from deamination of cytosine
Molecular

Which has a higher melting point: G-C or A-T?
G-C has three bonds making it stronger than A-T = G-C has a higher melting point
Molecular

What three aminoacids are necessary for purine synthesis?
Glycine
Aspartate
Glutamine
Molecular

What are nucleotides comprised of?
Base+ribose+phosphate = linked by 3'-5' phosphdiester bonds
Molecular

Transition vs Transversion
TransItion: Identical type
Purine substituted with purine

TransVersion: conVersion between types
Substituting purine for pyrimidine (much worse)
Molecular

Silent mutation
Same aa, often base change in 3rd position of codon (tRNA wobble)
Molecular

Nonsense codon
Nonsense: STOP the nonsense!!
It results in a stop codon
Molecular

Missense
Missense: "ha ha you MISSed me. you thought you changed me but you didn't!"

Changed aa is similar in chemical structure as the old one (conservation)
Molecular

What disorder is caused by nucleotide excision repair defect?
Xeroderma pigmentosa (dry skin with melanoma and other cancers)
Molecular

What type of mutation is involved in hereditary nonpolyposis colon CA?
Mismatch repair defect(in mismatch repair: unmethylated, newly synthesized string is recognized, mismatched nucleotides are removed, and the gap is filled and resealed.
Molecular

What is the smallest type of RNA?
tRNA
Molecular

What is the function of RNA Polymerase I, II, and III in eukaryotes?
I:makes rRNA
II: makes mRNA
III: makes tRNA

FA: I, II, and III are numbered as their products are used in protein synthesis
Molecular

What inhibits RNA polymerase II
alpha-amanitin (found in death cap mushrooms)
Molecular

Does RNA polymerase in eukaryotes have a proofreading function?
NO (but can initiate chains)
Molecular

What is the initial codon in mRNA?
AUG
Molecular

What does AUG code for in eukaryotes? prokaryotes?
Eukaryotes: codes for methionine, which may be removed before translation is completed.

Prokaryotes: codes for formyl-methionine (f-Met)
Molecular

What are three stop codons?
UGA: U Go Away
UAA: U Are Away
UAG: U Are Gone
Molecular

What is a promoter sequence?
AT-rich sequence (ex. TATA and CAAT)
Molecular

What is an operator?
A thing bound where negative regulators (repressors) bind.
Molecular

What are the three things that happen to the RNA after transcription?
1.capping on 5' end (7-methly-G)
2. polyadenylation on 3' end (200A's)
3. splicing out of introns

(capped and tailed transcript is called mRNA)
Biochem

What processes occur in the mitochondria?
Fatty acid oxidation, acetyl-CoA production, Krebs cycle.
Biochem

What processes are in the cytoplasm?
Glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), steriod synthesis (SER)
Biochem

What processes are in the both the mito and cytoplasm?
Gluconeogenesis, urea cycle, heme synthesis
Biochem

What are the five irreversible enzymes of glycolysis?
Hexokinase/glucokinase
phosphfructokinase
pyruvate kinase
citrate synthase
alpha ketoglutarate dehyrdrogenase
Biochem

What is S-adenosyl-methionine?
ATP+methionine--> SAM

SAM transfers methyl units.

Regeneration of methione (and thus SAM) is dependant on vitamin B12

"SAM the methyl donor man"
Biochem

Compare glucokinase to hexokinase?
Glucokinase: from liver, low affinity, high capacity, no feedback inhibition

Hexokinase (ubiquitous): high affinity, low capacity, feedback inhibition by glucose 6-phosphate.
Biochem

What is the most common glycolytic enzyme deficiency associated with hemolytic anemia?
Pyruvate kinase (if it doesn't have pyruvate kinase it can't make pyruvate to convert lactate for energy)