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Biochem > Clinical Cases and Correlations > Flashcards

Clinical Cases and Correlations Flashcards

1
Q

GP6D Deficiency

Causes

A

Most common genetic enzyme deficiency & most common cause of acute hemolysis

Occurs when:

  1. individual expresses < 50-60% of normal G6PD levels

AND

  1. body is subject to oxidative stress (H202) via infections, oxidant drugs (sulfa, bactrim), and fava beans
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2
Q

G6PD

Worldwide distribution

A

common in places where malaria is pandemic

hypothesized as an evolutionary adaptation against malaria due to increased destruction of plasmodium infected RBCs

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3
Q

G6PD

Cause of RBC destruction

A

Rise in H202 due to sub-optimal levels of NADPH

Oxidative damage to plasma membrane and hemoglobin in RBCs

Aggregated hemoglobin forms Heinz Bodies

Macrophages may engulf part of the membrane, causing characteristic “bite cells”

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4
Q

ETOH Hypoglycemia

2 Pathways

A
  1. in cytosol:
    - ETOH oxidized in rxns via alcohol dehydrogenase and aldehyde dehydrogenase
    - NADH (cyto) is produced in both rxns
  2. In smooth ER:
    - ETOH metabolized to acetaldehyde, feeds to aldehyde dehydrogenase rxn in cytosol, increasing NADH (cyto)
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5
Q

ETOH Hypoglycemia

Effects

A

Liver gluconeogenesis begins and become source of glucose in starvation states

High NADH levels drive rxns toward production of lactate and malate in cytosol.

Pyruvate and OAA are missing, so gluconeogenesis can’t happen.

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6
Q

Effect of Cyanide poisining

A

irreversibly binds to Fe3+ in ETC complex IV

Nitrates are the antidote, convert Fe2+ to Fe3+ which can bait cyanide before it reaches tissue

O2 is also administered

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7
Q

CO poisoning

A

CO binds to Fe2+ in complex IV, but less tightly than Cyanide.

Also binds to Fe2+ in hemoglobin, displacing O2

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8
Q

Niacin and Lipolysis

A

Pharmacologic levels of niacin inhibit lipolysis

Reduces production of VLDL and LDL

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9
Q

Ketogenesis and Diabetes

A

continued low I/G ratio leads to very active ketogenesis

Populations: untreated DM I, neonates consuming milk, adults on atkins diet

Ketonemia can occur, which can lead to DKA

Acetone, fruity odor in breath, sign of DKA

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10
Q

Fructokinase deficiency

A

benign condition

Fructose accumulates in the urine

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11
Q

Aldolase B deficiency

A

Fructose Poisoning

Mechanism:
1. hepatic accumulation of F1P due to metabolic block

  1. F1P is osmotically active, leading to liver damage and failure.
  2. Pi is tied up to make F1P, so Pi levels are decreased leading to decreased glycogenolysis and hypoglycemia
  3. Decreased Pi results in decreased ATP synth

THERAPY:
avoid dietary fructose and sucrose

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12
Q

Gal-1-P Uridyltransferase Deficiency
(Classic Galactosemia)

Mechanism

A
  1. metabolic block results in hepatic accumulation of Gal-1-P. Osmotic activity results in liver damage
  2. Galactose accumulates in liver and other tissues
  3. Galactose in the cell is converted to Galactitol by aldose reductase
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13
Q

Gal-1-P Uridyltransferase Deficiency
(Classic Galactosemia)

Presentation

A
  1. Galactosemia
  2. Galactosuria
  3. Liver damage due to increased Gal-1-P and galactitol
  4. Extrahepatic tissue damage
  5. Cataracts, kidney and nerve damage
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14
Q

Gal-1-P Uridyltransferase Deficiency
(Classic Galactosemia)

Therapy

A

Remove all dietary galactose including lactose containing foods and galactose containing compounds

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15
Q

Hypercholesterolemia (high LDL) drugs:

Statins

A
  • Competitive inhibitors, similar to HMG-CoA, inhibit cholesterol synthesis
  • Ex: lovastatin, simvastatin, atorvastatin

Mechanism:
1. Inhibition of HMG-CoA Reductase lowers cytosolic cholesterol

  1. LDL receptor synthesis is increased
  2. LDL mediated endocytosis is increased
  3. Decreased serum LDL
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16
Q

Hypercholesterolemia (high LDL) drugs:

Resins, Bile Acid Sequestrants

A
  • Charged resin to form ionic bonds with bile acids. Insoluble complex excreted in feces
  • Less bile acid/salt reabsorbed, more excreted.

Ex: cholestyramine, colestipol, colesevelam

Mechanism:
-Since more bile acids/salts are excreted, de novo synthesis using cholesterol as substrate needs to start in order to make up the difference.

-Increased use of cholesterol to produce more bile acids leads to lower cytosolic
cholesterol.

  • As a result, LDL-receptor synthesis is increased.
  • LDL-mediated endocytosis is increased.
  • HMG-CoA reductase activity is also increased.
  • This leads to decreased serum LDL-cholesterol
17
Q

Hypercholesterolemia (high LDL) drugs:

Cholesterol absorption inhibitors

A
  • Bind to protein cruicial for absorption in enterocytes and hepatocytes
  • Cholesterol absorption inhibited

Ex: ezetimibe

Mechanism:

  • Decreased absorption lowers cytosolic cholesterol
  • LDL receptor synthesis is increased
  • LDL endocytosis increased
  • HMG-CoA reductase increased
  • decreased serum LDL
18
Q

Hypercholesterolemia (high LDL) drugs:

Combo Therapy

A

Commonly Statins/Ezetimibe or Statins/Cholestyramine

19
Q

Familial Hypercholesterolemia

Presentation

A

Xanthomata- tumerous masses in subepithelial tissue of skin and tendons

Corneal Arcus

Atherosclerosis

20
Q

Familial Hypercholesterolemia

Lipid profile

A

extremely high LDL with normal TAGs

21
Q

Familial Hypercholesterolemia

Mechanism

A

defective LDL receptor leads to impaired serum LDL endocytosis

Serum LDL increases

Cytosolic cholesterol is lower, resulting in HMG-CoA Reductase activity and de novo synthesis

22
Q

Cholesterol Gallstones/Cholelithiasis

Risk factors

A
  • Fat (in men and women with either obesity or rapid weight loss)
  • Female
  • Forty (in women)

-Fertile (due to higher levels of estrogen, which increases cholesterol secretion into
bile)

-Fibrates (and other drugs that inhibit cholesterol 7-alpha-hydroxylase)

23
Q

Cholesterol Gallstones/Cholelithiasis

Causes

A

imbalance of free cholesterol and phospholipids/bile solvent secreted by liver

3 Factors:
1. increase in cholesterol secretion into bile

  1. Decrease in level of bile salts/phospholipids
  2. delayred/incomplete gallbladder emptying
24
Q

Cholesterol Gallstones/Cholelithiasis

Treatment

A

-Typically, surgical removal of the gallbladder (laparoscopic cholecystectomy) is
the treatment of choice.

-For patients unable to go through surgery, administration of exogenous
ursodeoxycholic acid (ursodiol, a bile acid) is used to supplement the body’s supply
of bile acids, resulting in a gradual (months to years) dissolution of the gallstones.

25
Q

Familial Chylomicronemia

Problem
Consequence
Lipid Profile
Presentation
Therapy
A

Problem: deficiency of LPL or apo C-II

Consequence: TAG in CM cannot be hydrolized

Lipid profile: Elevated fasting CM w/ high TAGs

  • Serum is turbid/milky
  • VLDL not elevated

Presentation:

  • Eruptive Xanthomata after meal
  • Pancreatitis

Therapy:

  • consumption of medium and short chain TAGs
  • Fat soluble vitamin supplementation
26
Q

Abetalipoproteinemia

CM Retention Disease

A

Problem: loss of function in MTP gene due to mutation

Consequence: TAGs not transferred to CM and VLDLs, cannot be assembled

Lipid Profile: CM, VLDL, LDL absent, hypolipidemia

Presentation:

  • Failure to thrive
  • Dietary fat accumulation in enterocytes
  • Steatorrhea
  • neuro deficits

Therapy:
-Low fat, calorie rich diet w/ vitamin supplementation

27
Q

familial combined hyperlipidemia type IIb

Causes
Consequences
Lipid Profile
Clinical Presentation
Therapy
A

1o cause: overproduction of apo B-100

2o cause: obesity, metabolic syndrome, insulin resistance

Consequence: excessive VLDL production

Lipid Profile: decreased HDL, elevated VLDL and LDL

Presentation:

  • Few manifestations
  • High risk of premature CVD

Therapy:

  • combo therapy of niacin and statins, resins
  • diet and lifestyle
28
Q

familial disbetalipoproteinemia type III

Causes
Lipid Profile
Clinical Presentation
Therapy

A

1o: poor apo E2 binding to Apo E receptor due to polymorphism of apo E gene
2o: high fat, DM, obesity, ETOH, hypothyroidism, estrogen deficiency

Lipid profile: elevated IDL and CM remnants

Presentation:

  • Turboeruptive xanthomata
  • palmar striated xanthomata
  • high risk of CVD PAD

Therapy:
-combo therapy niacin, fibriates and statins,resins

29
Q

Tangier disease (alpha-lipoprotein deficiency)

Causes
Consequences
Lipid Profile
Clinical Presentation
Therapy
A

Cause: ABCA1 def.

Consequence: cholesterol accumulation in tissue, nascent HDL degradation, impaired transfer of Apo E and Apo C-II

Lipid Profile: low HDL and LDL

Presentation:

  • enlarged orange tonsils
  • MI
  • Clouding cornea
  • peripheral neuropathy

Treatment:
NONE

30
Q

Niacin

A

Lower TAGs: inhibits HSL and lipolysis decreasing VLDL and LDL production

Increase serum HDL: decreases Apo A-I breakdown, extending HDL life

31
Q

Fibrates

A

Lower TAGs: activate LPL, VLDL clearance in creased. Secretion of nascent VLDL decreased

Increase serum HDL: increase Apo A-I expression

Biochem (9 decks)

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