Diseases and Disorders Exam 6

Question 1

Beriberi

Answer 1

• Thiamine (B1) deficiency
• can be dry or wet
• characterized by dry skin, irritability, disordered thinking, forgetfulness, paralysis
• most common in alcoholics

Question 2

Wernicke-Karsokoff

Answer 2

• thiamine deficiency d/t alcohol consumption
• decreased activity of PDH and alpha-KG DH
• sx: mental derangement, memory loss, ataxia
• tx: thiamine injections

Question 3

Pellagra

Answer 3

• Niacin (B3) deficiency
• reduced NAD and NADP
• sx: rough skin
• 4D disease: dermatitis, diarrhea, dementia, death

Question 4

Sideroblastic anemia

Answer 4

• vitamin B6 deficiency (PLP)
• microcytic, hypochromic anemia with normal Fe levels
• other sx of B6 deficiency: glossitis, psychiatric sx, seizures (d/t low GABA)

Question 5

Biotinase Deficiency

Answer 5

• causes a biotin (B7) deficiency

- sx: dermatitis, alopecia, glossitis, loss of appetite, nausea

Question 6

Pernicious anemia

Answer 6

• vitamin B12 deficiency
• neurological sx (b/c lack of myelin)
• megaloblastic anemia

Question 7

Copper Deficiency

Answer 7

• sx: microcytic hypochromic anemia, hemorrhagic vascular changes, bone demineralization, neurologic problems

Question 8

Menke’s Disease

Answer 8

• deficiency of ATP-dependent membrane Cu- transporter in the intestine
  low Cu levels

Question 9

Wilson Disease

Answer 9

• mutation in Cu transporter in the kidney which decreases excretion and increases Cu levels
• sx: liver damage, neurological and hematological complications

Question 10

Vitamin A deficiency

Answer 10

• causes vision problems

- can cause metaplasia of corneal epithelium where epithelial cells are transformed to keratinized squamous epithelia

Question 11

Vitamin K deficiency

Answer 11

• Vit K responsible for carboxylation of glutamic acid which creates Ca binding sites on blood clotting factors
• deficiency leads to easy bruising, increased prothrombin time
• associated with fat malabsorption, long-term antibiotic use, breast feeding

Question 12

5-Flourouracil

Answer 12

inhibits thymidylate synthase, causes thymine less death

Question 13

Methotrexate

Answer 13

folate analog that competitively inhibits DHFR and leads to thymine less death

Question 14

Hyperhomocysteinemia

Answer 14

• can be caused by lack of folate, B12 or B6
• increased risk of cardiovascular events
• oxidizing agent that inactivates NO and alters coagulation

Question 15

Gout

Answer 15

• increase in uric acid
• can be caused by a gain of function mutation in PRPP synthetase, leading to an increase in purine synthesis and therefore an increase in purine breakdown
• tx: allopurinol which is an inhibitor of xanthine oxidase. Works bc xanthine is easier to excrete

Question 16

Lesch-Nyhan Syndrome

Answer 16

• mutation in HGPRT
• causes an increase in PRPP levels bc not being used in salvage pathway which increases purine de novo synthesis and therefore breakdown causing an increase in uric acid levels
• sx: intellectual disability and self mutilation

Question 17

ADA Deficiency

Answer 17

• deficiency in adenosine deaminase which leads to an accumulation of adenosine
• excess adenosine is converted to AMP by adenosine kinase
• increased AMP increases dATP which inhibits RR consequently decreased dGTP
• affects fast dividing cells -> SCID

Question 18

Orotic Aciduria (UMP-Synthase deficiency)

Answer 18

• impaired pyrimidine synthesis pathway
• sx: poor growth, megaloblastic anemia
• increased orotate
• normal BUN and ammonia

Question 19

Iron Deficiency

Answer 19

• causes microcytic, hypochromic anemia
• lack of iron causes Zn to be inserted instead
• ZnPP is a clinical indicator

Question 20

Lead Poisoning

Answer 20

• Lead is an inhibitor of ALA dehydrogenase and ferrochelate which decreases heme production
• lead does not get inserted into PP IX
• anemia
• delta-ALA and PP IX accumulate in the urine and blood -> look for this to diagnose

Question 21

Acute Intermittent Porphyria (AIP)

Answer 21

• deficiency of uroporphyrinogen I synthase
• function most significantly decreased in the liver
• ALA and porphobilinogen accumulate in the blood and CSF
• sx often misdiagnosed as psychosomatic and the drugs pts are put on induce cytochrome p450 which binds up heme and exacerbates patients sx.
  Tx: hematin (stable form of heme) and high carb diet

Question 22

Porphyria cutanea tarda

Answer 22

• deficiency of uroporphyringen decarboxylase
• usually seen in alcoholics
• worse with iron overloading (causes iron overloading?)
• can’t go out in sunlight

Question 23

Prehepatic (hemolytic) jaundice

Answer 23

• increase in bilirubin in blood bc RBC burst
• increase in conjugated and unconjugated in blood
• low plasma hapatoglobin bc excess heme binds to it

Question 24

Intrahepatic jaundice

Answer 24

• impaired liver function
• increase in unconjugated, decrease in conjugated
• pale stools
• increased AST and ALT

Question 25

Gilbert’s Syndrome

Answer 25

• defective UDP-glucuronyl transferase
• leads to occasional jaundice (intrahepatic)
• onset in 20’s
• tx: phenobarbital to stimulate enzyme

Question 26

Posthepatic jaundice

Answer 26

• obstruction after liver
• increase in conjugated
• dark urine, pale stool
• can lead to liver damage and consequently an increase in unconjugated as well

Question 27

Neonatal jaundice

Answer 27

• babies have late onset of glucouronyl transferase and also a delay in adult Hb replacing fetal Hb which can lead to a back up of unconjugated bilirubin

Question 28

Kernicterus

Answer 28

• unconjugated bilirubin is toxic to babies and can cross blood-brain barrier
• leads to mental retardation
• tx: put baby under a blue light which converts bilirubin to a more soluble form

Question 29

Hereditary Hemochromatosis

Answer 29

• excess iron in cells
• mutation in HFE gene
• normally HFE binds to the transferrin receptor and reduces its affinity to decrease amount of iron brought in
• not functional in HH -> increased iron absorption
• Hemosiderin deposits seen in the liver, pancreas, skin and joints
• sometimes shows up after menopause

Question 30

Grave’s Disease

Answer 30

• autoimmune: IgG binds to TSH receptors and causes excessive T3/T4 production
• decreased TSH in blood
• sx: weight loss, tachycardia, increased BMR
• Tx: corticosteroids to inhibit deiodinase and prevent conversion of T4 to T3

Question 31

Parkinson’s

Answer 31

• loss of dopaminergic neurons in the substantia nigra
• sx: tremor, gait problems, rigidity, bradykinesia
• lewy bodies seen in microscope

Question 32

Albinism

Answer 32

• mutations in tyrosine hydroxylase or other enzymes in melanin pathway

Question 33

Pheochromocytoma

Answer 33

• NE/Epi secreting tumor

- look for elevated VMA in blood

Question 34

Tyramine Poisoning

Answer 34

• MAO usually breaks down tyramine, so when on MAO inhibitors tyramine can build up
• worse when eating tryramine containing foods
• increased tyramine increases NE which raises BP

Question 35

Obesity

Answer 35

• mutation in MC4-R receptor can interrupt leptin signaling

- pt will never feel full and get fat

Question 36

Kwashiorkor

Answer 36

• inadequate intake of protein with adequate energy intake
• pt’s have edema bc of decreased plasma proteins
• also stunted growth, brittle hair, diarrhea, dermatitis, fatty liver

Question 37

Marasmus

Answer 37

• inadequate intake of protein and energy

- thin wasted appearance

Question 38

Sarcopenia

Answer 38

• muscle wasting
• d/t aging or inactivity
• tx: good exercise and diet

Question 39

Cystinuria

Answer 39

• problem with transporter in kidney and cystine cannot get reabsorbed so its peed out
• cystine not very soluble and can cause stones
• lysine, ornithine and arginine also use the same transporter so can see if these are elevated in urine too

Question 40

Maple Syrup Urine

Answer 40

• accumulation of branched-alpha ketoacids in blood and urine d/t deficiency of alpha-ketoacid DH
• from breakdown of leucine, isoleucine and valine
• sx: mental retardation, abnormal muscle tone, ketosis, coma, death

Question 41

PKU

Answer 41

• deficiency of phenylalanine hydroxylase (which requires BH4)
• build up of phenylacetate and phenyllactate bc Phe not being converted to Tyr
• sx: mental retardation, microcephaly, musty urine
• tx: diet and avoid aspartane

Question 42

Alcapronuria

Answer 42

• deficiency of homogentisate oxidase so cant break down tyrosine into fumarate and acetoacetate
• sx: dark urine, dark joints, arthritis

Question 43

Homocysteinuria

Answer 43

• can be a deficiency of homocystein methyltransferase (B12 and folate), cystathione synthase (PLP) or cystathione lyase (PLP)
• look for methylmalonic aciduria to diagnose a B12 deficiency
• sx: dislocated lens, DVT, stroke, athrosclerosis, mental retardation

Question 44

Hyperammonemia I

Answer 44

• deficiency of CPS I
• increase in ammonia, decrease in BUN
• NO increase in uracil and orotic acid in blood and urine

Question 45

Hyperammonemia II

Answer 45

• deficiency of ornithine transcarbamoylase
• increase in ammonia, decrease in BUN
• increase in uracil and orotic acid in blood and urine
• pyrimidine synthesis stimulated

Question 46

Hydroxyurea

Answer 46

• inhibitor of ribonucleotide reductase

- tx for CML

Question 47

GLP-1 agonists and DPP-4 inhibitors are used to treat what and how do they work?

Answer 47

• type 2 DM
• agonists stimulate insulin secretion
• inhibitors prevent degradation of GLP-1 and therefore promote insulin secretion