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FoundSci Unit 4 > Clinical Correlations > Flashcards

Clinical Correlations Flashcards

1
Q

How does a patient present when they have too low of fatty acid catabolism?

A

Fatty acid catabolism is meant to provide alternative to glucose for ATP production during fasting/

Liver unable to conduct gluconeogenesis (low ATP)

Insulin responsive tissues keep burning glucose instead of fat during fasting

Fasting hypoglycemia with absence/low ketones and metabolic acidosis

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2
Q

How does a patient present when they have too high of fatty acid metabolism?

A

Fatty acid metabolism supposed to be shut off in fed state.

Insulin insufficiency (diabetes) lead to fatty acid mobilization in fed state

Hyperlipidemia with high concentration of ketones

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3
Q

What are disorders of Mitochondrial fatty acid import and how do patients present?

A

Defects in any part of carnitine shuttle affect muscle function because muscle uses FA even in fed state. Defects range from cramping to cardiomyopathy, death in infancy.

Fasting hypoglycemia

Genetic: CPTI and CPTII deficiency

Genetic/Nutritional: Primary carnitine deficiency - strict vegetarian diet so poor uptake and transport of carnitine

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4
Q

How do patients present with Beta-Oxidation disorders?

A

MCAD deficiency is most common FA degradation disorder - Medium Chain Acyl-CoA dehydrogenase

Results in hypoketotic fasting hypoglycemia

Accumulation of C6-C12 FA in urine, acyl-carnitines in blood

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5
Q

Zellweger Syndrome

A

Mutation in PEX gene. Peroxisome biogenesis disorder

Results in multiple developmental abnormalities. No peroxisomes in liver

Dx: Accumulation of very long chain fatty acids in blood

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6
Q

Refsum Disease

A

Alpha-Oxidation Deficiency. Peroxisome Biogenesis Disorder

Multiple developmental abnormalities

Dx: Accumulation of phytanic acid in blood

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7
Q

Primary Dyslipidemia

A

Abnormal Concentration of serum lipids.

Congenital disorders caused by mutations in lipoprotein metabolism - common in children, inherited by affected parent

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8
Q

What do defects in lipoprotein synthesis cause?

A

Hypolipidemia

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9
Q

What do defects in lipoprotein unloading cause?

A

Hyperlipidemia

Elevated TG and/or cholesterol

Risk of cardiovascular disease

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10
Q

Patient presents with corneal arcus. Family history of hypercholesteremia. Physical examination shows fatty deposit on Achilles tendon and knuckles. Lab shows 2x elevated cholesterol and normal TG. What lipoprotein is affected?

A

LDL because they mainly carry cholesterol.

This is Fredrickson IIa.

LDL could be elevated for many reasons such as
- Does not bind to receptor
- Receptor defective -> familial hypercholesteremia
- ApoB100 defective - familial defect ApoB100 or phenocopy of FH (detection of mutation)

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11
Q

What if a patient present with high TG and cholesterol? What lipoproteins could be affected?

A

LDL
VLDL
chylomicron remnants

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12
Q

What if a patient presents with elevated TG? What lipoprotein is impacted?

A

Chylomicrons and VLDL

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13
Q

What are secondary dyslipidemias?

A

Consequences of other metabolic disorders or disturbances.

Most frequent in adult

Often caused by poor diet, diabetes, alcohol abuse

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14
Q

Hypercholesterolemia

A

High LDL

Raises cardiovascular risk

Primary hypercholesterolemia - present in infancy

Secondary hypercholesterolemia - presents in adulthood, sedentary lifestyle, cholesterol rich diet, smoking

Statin drugs lower LDL by inhibiting endogenous cholesterol synthesis

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15
Q

Patient presents with complaints of sharp pain in upper right quadrant of abdomen and nausea. Jaundice, elevated serum bilirubin, elevated alkaline phosphatase.

A

Labs indicate cholestasis - flow of bile impaired. Bilirubin and AP not secreted into gut

Gallstones - contain cholesterol, bile acids, phospholipids, and bilirubin. Caused most often by precipitation of cholesterol

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16
Q

How does plasmalogen levels related to Alzheimer Disease?

A

Low levels of plasmalogen were found to be correlated with severity of AD.

Plasmalogen is an abundant phospholipid and enriched in CNS and brain

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17
Q

Gaucher Disease

A

Sphingolipid disorder and lysosomal storage disease.

Patient presents with splenomegaly and bone pain. Bone marrow biopsy shows Gaucher cells (macrophages filled with undegraded sphingolipids)

White blood cells show low glucocerebroside activity

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18
Q

How does a patient present with lysosomal storage diseases?

A

Congenital, progressive, and recessive disorders.

Generally involve the spleen since it is lysosomal rich.

Sphingolipidosis - accumulation of lipids often in brain

Mucopolsaccharidoses - Accumulation of acidic carbohydrate (GAG)

Less common - Pompe which is accumulation of glycogen

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19
Q

What do steroids, NSAIDs, and LOX inhibitors suppress?

A

Eiconsanoid signaling!

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20
Q

What are some eicosanoids?

A

Prostaglandins - mediate inflammation and pain

Thromboxanes - facilitate blood clotting

Leukotrienes - mediate asthma and allergy

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21
Q

Acute Pancreatitis

A

Patient presents with abdominal pain, nausea, vomiting, pancreatic necrosis if advanced

Caused by alcohol, gallstones, infections. Premature activation of trypsin within the pancreas

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22
Q

Patient present with abdominal pain and cramping upon consuming gluten and nutrient deficiency.

A

Celiac Disease

Causes are incomplete digestion of gluten. due to loss of brush border peptidase, alpha-gliadin triggers inflammatory response, and a loss of villi and flat small intestines

Treat with gluten free diet

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23
Q

Hartnup Disease

A

Caused by deficiency in sodium dependent transporter of neutral amino acids across the intestine and kidney membranes.

Impacts the intestinal absorption of amino acids and kidney reabsorption of amino acids

Symptoms include pellagra like light sensitive rash (lack of tryptophan, precursor of niacin) and neutral amino acid aciduria

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24
Q

What lab test informs us about liver damage?

A

ALT - Alanine amintotransferase

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25
Q

Patient present with elevated levels of homocysteine in urine.

A

Homocystinuria

Caused by defect in cystathionine Beta-synthase which converts homocysteine to cystathionine

26
Q

Cystathioninuria

A

Rare autosomal disorder in gene encoding cystathionine gamma-lyase which converts cystathionine to cysteine

Patient presents with elevated levels of cystathionine in blood and urine

27
Q

Phenylketonuria

A

Caused by genetic defect in phenylalanine hydroxylase (more common) or in DHBtn reductase

Dx metabolites: Phenylpyruvate and phenylalanine

Symptoms include intellectual disability, recurrent seizures, and hypopigmentation

28
Q

What is the mechanism of Phenylketonuria?

A

Accumulation of Phenylalanine competitively inhibits the transport of other amino acids across blood brain barrier and so interferes with neurotransmitter synthesis

Can impact formation of myelin, dopamine

Phe is competitive inhibitor of tyrosinase and so interferes with melanin (skin pigment)

29
Q

What is the treatment for phenylketonuria?

A

Newborn screening
Low dietary Phe
Supplement with tyrosine

30
Q

Why is aspartame toxic to people with phenylketonuria?

A

Aspartame is an artificial sweetener made of aspartate and phenylalanine

So when it is degraded, it releases Asp, Phe, and methanol

The Phe is toxic to people with PKU

31
Q

Symptoms include elevated glycine, seizures, lethargy, and lack of muscle tone (hypotonia)

A

Glycine Encephalopathy

Mutations in glycine cleavage system

Known as nonketotic hyperglycemia

31
Q

Familial Hyperinsulinemic Hypoglycemia Type 6 (HHF6)

A

Caused by rare mutation in GLUD1 that encodes GDH

Glutamate dehydrogenase become insensitive to GTP inhibition

Symptoms appear during high protein meal.

Leads to hyperammonemia - elevated ammonia levels, less N-acetylglutamate for urea cycle

Hypoglycemia - increased ATP promotes insulin releases

31
Q

Propionic Acidemia

A

Loss of propionyl-CoA carboxylase

Accumulation of propionic acid because of increased propionyl-CoA (not being broken down)

Symptoms incudes metabolic acidosis leading to severe ketoacidosis, vomiting, rapid breathing, and lethargy

32
Q

Methylmalonic aciduria

A

Caused by either defect in mutase or deficiency in Vitamin B12 results in accumulation of methylmalonate in serum and urine.

Mutase with Vit B12 converts L-methylmalonyl-CoA to succinylCoA

33
Q

Vitamin B12

A

Water soluble

Bacteria is only source but can be found in animal products of ruminants

34
Q

What are the types of Vitamin B12 deficiencies?

A

Actual B12 deficiency - Lack of B12 in diet

Functional B12 deficiency - Inability to absorb or metabolize B12

Pernicious Anemia - lack of intrinsic factor that binds B12 in ileum. Can cause organ specific autoimmune disease and is dx by presence of antibodies against the intrinsic factor

35
Q

What is the biochemical basis of Vit B12 deficiency?

A

Non-functional methionine synthase causes trapping of THF as N5-methyl-THF. This leads to decrease in N5N10-methylene THF and blocks DNA replication

Folate can restore purine and thymidine synthesis but cannot prevent homocysteine synthesis

Non-functional mutase (catabolism of Ile, Val, Thr, Met) causes accumulation of methylmalonate and malonate. Folate cannot prevent methylmalonate accumulation.

36
Q

What is the clinical basis of Vitamin B12 deficiency?

A

Megaloblastic anemia - Impairment of DNA synthesis causes production of marge, immature, hemoglobin poor red blood cells in bone marrow

Demyelination

Atherosclerosis - high homocysteine

Dx metabolites: methylmalonate, methylmalonyl-CoA, and homocysteine

37
Q

Maple Syrup Urine Disease

A

Deficiency in branched chain keto acid dehydrogenase (BCKDH)

Dx metabolites: High branched chain amino acids in blood and high branched chain ketoacids in the urine

Symptoms include maple syrup odor of urine (branched chain alpha keto acids) and brain edema

38
Q

Tyrosinemia II

A

Inborn error in tyrosine degradation pathway. Loss of tyrosine aminotransferase which converts tyrosine to 4-hydroxyphenol pyruvate

Symptoms include keratitis and photophobia

Treat with diet low in Phe and tyrosine

39
Q

Patient presents with black urine and joint destruction. Patient has elevated levels of homogentisate and alkaptone

A

Alkaptonuria

Loss of homogentisate oxidase

Treatment with nitisinone - inhibits conversion of 4-hydroxyphenopyruvate to homogentisate

40
Q

Tyrosinemia I

A

Inborn error in tyrosine degradation

Loss of fumarylacetoacetate hydrolase

Dx Metabolites: Succinylacetone

41
Q

Early Step Urea Cycle Enzyme Deficiencies

A

More severe

Deficiency in either carbamoyl phosphate synthetase I or ornithine transcarbamoylase

Resuls in severe hyperammonemia

42
Q

Late step urea cycle enzyme deficiencies

A

Less toxic

Citrullinemia - loss of argininosuccinate synthetase. Dx metabolite is citrulline

Argininogsuccinic Aciduria - loss of argininosuccinate lyase. Dx metabolite is argininosuccinate

Hyperargininemia - loss of arginase, Dx metabolite is arginine

43
Q

How are patients with early urea cycle disorder treated?

A

Protein restriction

Removal of ammonia ions independent of urea formation - phenylbutyrate and benzoate form water soluble conjugates with glutamine and glycine

Liver transplant

44
Q

How are patient treated with late urea cycle disorders?

A

Dietary intervention - supplement with arginine

Removal of ammonia ions independent of urea formation - phenylbutyrate and benzoate form water soluble conjugates with glutamine and glycine

45
Q

What can indicate kidney impairment?

A

Changes in serum creatinine

46
Q

How do patients with creatine metabolism disorders present?

A

Children present with hypotonia

Variety of neurological symptoms - seizures, intellectual disability

Treat with creatine

47
Q

Parkinson’s Disease

A

Degeneration of dopaminergic neurones

Usually in people over 60

Loss of involuntary muscle control

Relief by administration of DOPA

48
Q

Oculocutaneous albinism type I (OCA1)

A

Most common

Loss of function of tyrosinase so inability to synthesize melanin in skin, hair, and eyes

Complications include impaired vision and early appearance of skin tumors

49
Q

Pellagra

A

Diets lows in niacin, tryptophan, or cofactors required for niacin synthesis

Hartnup - Uptake of certain amino acids from blood and reabsorption by kidney blocked. pellagra can result, treated with high protein/niacin diet.

50
Q

Dry PEU - Marasmus

A

Patient starves for glucose and protein

51
Q

Wet PEU, Edema - Kwashiorkor

A

Starves severely for protein

Labs may show low albumin, transferrin, white blood cell count. Patient may present with lethargy and weakness

52
Q

Cachexia

A

Involuntary Weight Loss. Comorbidity of cancer and other wasting diseases (COPD, heart disease, kidney disease)

53
Q

Type II Diabetes

A

Inadequate insulin response

Patient complains of thirst and frequent urination and increased dizziness. Physical exam shows patient is overwieght with signs of dehydration

Acanthosis nigricans in neck region. High blood sugar and serum insulin is elevated

Treat by suppressing gluconeogenesis, lipolysis

54
Q

Type I Diabetes

A

Inadequate insulin secretion

Patient experiences thirst and frequent urination. Dehydration, dizziness, and abdominal pain. Insulin level is low

Treat with insulin

55
Q

What are common complications of diabetes?

A

Hyperglycemia - damages blood vessels and starves tissues

Retinopathy - leads to blindness

Nephropathy - chronic renal failure

Neuropathy - numbness

56
Q

What are molecular causes of insulin resistance?

A

Inhibitory phosphorylation of IRS proteins

Loss of FoxO1a inhibition

Low PDK1 activity

57
Q

How does a patient present with Hyperinsulinemia?

A

Hypoketotic hypoglycemia

Inappropriately high insulin

Supress fatty acid metabolism

58
Q

What are biochemical markers for Diabetes Management?

A

Glycated Hemoglobin - HbA1c - less than 5.7%

C Peptide - indicates endogenous insulin production

Beta cell specific antibodies - glutamic acid decarboxylase antbodies indicate autoimmune reaction against beta cells

FoundSci Unit 4 (11 decks)

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