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Flashcards in DIT Part 2 Deck (255):
1

What happens in ketogenesis

in the liver, Fatty acids and Amino Acids are metabolized to acetoacetate and then (with NADH) to beta-hydroxybutyrate. These are to be used in muscle and brain

2

What are the main ketone bodies

Acetoacetate
Beta-hydroxybutyrate

3

RLS for ketone synthesis

HMG-CoA synthase (NOT REDUCTASE)

4

Acetoacetate sponteously becomes

Acetone
(note the fruity smell to breath)

5

Urine test for ketone bodies tests for

Tests for Acetoacetate

NOT beta-hydroxybutyrate

6

Why does drinking alcohol stop gluconeogenesis

Liver regenerates NAD+ by converting pyruvate to lactate

converting oxaloacetate to malate

resulting in a severe fasting hypoglycemia by patients who consume a lot of alcohol in a fasting state

7

what can the body do with acetyl-CoA

TCA cycle
FA synthesis
Cholesterol synthesis
Ketone synthesis

8

What is seen in kwashiokor

FLAME
-Fatty Liver (no production of ApoB-100, to make particles with cholesterol and triglycericdes)
-Anemia
-Malnutrition
-Edema

(also skin lesions and depigmentation of skin and hair)

9

what happens in Refeeding syndrome?

drop in serum levels of mg, phosphate potassium which can lead to arrhythmias and neurological problems

Overall depletion of ATP

Why you need to take it slow and monitor

10

What are risks for hepatocellular carcinoma

Hep B and C
Hemochromatosis
alpha1-antitrypsin deficiency
Hepatic adenoma
Any type of Cirrhosis

11

TCA overdose symptoms

convulsions
coma
cardiotoxicity

hyperpyrexia
respiratory depression

12

Apo B-48

Chylomicron secretion from enterocyte to lymphatic system

13

ApoB-100

Found on VLDL, IDL, and LDL

14

Apo E

Mediates extra remnant uptake

15

Apo A-I

Activates LCAT, found on HDL

16

Apo C-II

Cofactor for lipoprotein lipase

17

Chlylomicron has what apoproteins

Apo E, Apo A-I, Apo C-II, Apo B-48

18

Chylomicron remnant has what apoproteins

Apo E, Apo B-48

19

VLDL has what apoproteins

Apo E, Apo C-II, Apo B-100

20

IDL has what apoproteins

Apo E, Apo B-100

21

LDL has what apoproteins

Apo B-100

22

HDL has what apoproteins

Apo E, Apo A-I Apo C-II

23

Abetalipoproteinemia mechanism

Presentation

Autosomal recessive disorder with decrease in ApoB-48 and ApoB-100

mech: inability to generate chylomicrons, cecreased secretion of cholesterol, VLDL into bloodstream, fat accumulation in enterocytes


Presents w/
-Failure to thrive in early childhood
-Steatorrhea
-acanthocytosis (spikey RBC due to alteration in membrane lipids)
-ataxia
-night blindness

24

treatment of abetalipoproteinemia

Vitamin E

25

Type I hyperchylomicronemia

Mechanism

Presentation

Is it a risk factor for atherosclerosis

Autosomal recessive

Mech: Deficiency of lipoprotein lipase
or
Defective apolipoprotein C-II

Presentation: Pancreatitis (from increased triglycerides), hepatosplenomegaly, pruritic xanthomas

No increased risk for atherosclerosis

26

Type IIa familial hypercholesterolemia

Mechanism

Presentation

Autosomal dominant

Mech: Absent or decreased LDL receptors.

Presents with Tendinous xanthomas (achilles), Corneal arcus, accelerated atherosclerosis, MI in 20s (for double dominant mutation)

27

Type IV hypertriglyceridemia

Mech:

Presentation

Autosomal dominant

Mech: Overproduction of VLDL

Pancreatitis (from increased triglycerides)

28

Signs of hyper cholesterolemia

Atheromas, plaques in blood vessel wall-oxidized LDL

Xanthomas- plaques or nodules of histiocytes filled with lipid. esp around eyelid.

Xanthelasma-xanthoma on eyelid

Tendinous xanthomas-commonnly achilles, elbows,

Corneal arcus-lipid deposition in the cornea

29

Fatty acid synthesis:
Precursor,Location, RLS

Acetyl-CoA is precursor, occurs in cytoplasm of hepatocytes, RLS is Acetyl-CoA carboxylase

30

Fatty acid degrdation:

Location

RLS

located in mitochondria, RLS is Carnitine acyltransferase-1 (aka carnitine palmitoyl transferase-1)

31

What is seen in carnitine deficiency? mechanisms and presentation

Inability to transport long chain fatty acids into the mitochondria, resulting in toxic accumulation

Presents as weakness, hypotonia, hypoketotic hypoglycemia.

32

What are the essential amino acids

Private (PVT) TIM HaLL

-Phenylalanine
-Valine
-Threonine
-Tryptophan
-Isoleucine
-Methionine
-Histidine
-Arginine
-Leucine
-Lysine

33

Basic AAs

Lysine and arginine (extra ammonia group, positve charge at body pH)

Histidine (although basic, has no charge at body pH)

Arginine and histidine (during periods of growth)

Arginine and lysine (NLS, high concentrations in histones)

34

Acidic AAs

Aspartate and glutamate
-negatively charged

35

Phenylalanine to Epi

Phenylalanine
Tyrosine
Dopa
Dopamine
NE
Epi

36

What can arginine be turned into

Creatine
Urea
Nitric oxide

37

Vitamin B6 dependent AA derivatives

Ia. Tryptophan to Niacin to NAD/NADP
Ib. Tryptophan to Serotonin to Melatonin

II. Histidine to Histamine

III. Glycine to porphyrin to Heme

IVa. Glutamate to GABA
IVb. Glutamate to Glutathione

38

RLS for Heme synthesis

Aminolevulinic synthase

39

Urea cycle RLS

Carbamoyl phosphate synthetase- I

40

CPS I vs. CPS II

CPS I gets nitrogen from ammonia, works in the mitochondria, and is in the urea cycle

CPS II gets nitrogen from glutamine, works in the cytosol, and is in the pyrimidine synthesis

41

Ornithine transcarbamylase deficiency

Presentation

Most common urea cycle disorder.
X linked recessive
Present in first few days of life
Orotic acid in the blood and urine
BUN is going to be decreased
Hyperammonemia

42

Symptoms of hyperammonemia

Slurring of speech
Somnolence
Vomiting
Cerebral edema
Blurring of the vision

43

Treating hyperammonemia

Low protein diet

If urea cycle problem:
Phenylbutyrate
Benzoate
Biotin (stimulate ornithine transcarbamylase)

44

PKU causes

2 ways
either missing phenylalanine hydroxylase
or
missing BH4 (tetrahydrobiopterin)

45

Why do you get neurotoxic effects in PKU

from high levels of phenylalanine, not due to phenylketones

46

what are the phenylketones

phenylacetate
phenyllactate
Phenylpyruvate

47

s/s of pku

growth retardation
mental retardation
seizures
fair skin (no melanin)
eczema
musty body odor

48

dx of pku

tx

screen at 2-3 days

treat within first 3 wks of life

tx: avoid phenylalanine (aspartame, dairy products,), augment tyrosine into diet, BH4 supplement could be necessar.

49

What happens to infant in gestational pku

phenylketones are toxic
-microcephaly
-intellectual disability
-growth retardation
-congenital heart defects

50

Alkaptonuria mechanism

congenital autosomal recessive and benign deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate.

51

s/s in alkaptonuria

dark connective tissue, brown pigmented sclerae, urine turns black on prolonged exposure to air. Debilitating arthralgias

52

Albinism causes

-Tyrosinase deficiency
-Defective tyrosine transport
-Abnormal neural crest migration of melanocytes

53

what is a consequence of albinism

skin cancer more likely

54

Homocystinuria causes

1. Deficiency of cystathionine synthase
2. Decreased affinity of the cystathionine synthase for the pyridoxal phosphate
3. Deficiency of homocysteine methyltransferase

55

S/S homocystinuria

mental retardation,
tall stature,
osteoporosis
kyphosis
Atherosclerosis
Subluxation of the lens (downward dislocation, c/f with marfans with upward dislocation

56

Cystinuria cause

defect of the renal tubular AA transporter for COLA (cysteine, ornithine, lysine, arginine), normally in the convoluted proximal tubule

57

s/s of cystinuria

tx

Cysteine kidney stones

tx: acetazolamide to prevent

58

Maple syrup urine disease cause

Deficiency of branched chain alpha-ketoacid dehydrogenase complex supposed to break down..

Isoleucine
Leucine
Valine

alpha ketoacids build up in the urine and blood

59

maple syrup urine disease s/s

intellectual deficiencies
Severe CNS defects

60

Hartnup cause

Autosomal recessive defect of transporter in intestine and kidneys leading to deficiency of neutral AA (tryptophan)

61

Hartup s/s

Pellagra (vitamin B3 deficiency)
Dermatitis
Diarrhea
Dementia

62

Vitamin D toxicity causes

Too much vitamin D supplementation

Sarcoidosis (increase in conversion of 25-OH D3 to 1,25-OH D3)

63

Vitamin K deficiency causes

Medications
-Coumadin
-Anticonvulsants (phenytoin)
-Antibiotics

64

Types of Vitamin A

Retinol
Retinal
Beta-carotene (cleaved in intestine to 2 molecules of retinol)
Retinoic acid not useful in body, but useful for treatment of certain diseases

65

Uses for Vitamin A

Mild to moderate acne (tretinoin)
Mild severe acne (isotretinoin)
[decrease size and secretion of sebaceous glands]

Measles treatment

AML (M3 subtype)

66

Vitamin A deficiency

Night blindness

Xerophthalmia (pathologic dryness of conjunctiva and cornea resulting in -->corneal ulcerations and blindness)

Keratomalacia (wrinkling and clouding of the cornea)

Bitot spots (bulba conjucntiva, dry silvery gray plaques)

67

Vitamin A toxicity

headache

N/V

Stupor

Increase in ICP (pseudotumor cerebri)

Dry and pruritic skin

Beta carotene skin orange which is not toxic.

Hepatomegaly

Cirrhosis

Bone and joint pain

Alopecia

68

What presentation of vitamin A toxicities can be seen

livers of bears (polar bears, or otherwise)

Pregnant mothers (teratogenic)

69

Vitamin E other name

alpha-tocopherol

70

What does vitamin E do

antioxidant, prevents non-enzymatic oxidation of cell components by free radicals (especially important for RBC)

71

vitamin E deficiency

hemolytic anemia

spinocerebellar degeneration resulting in ataxia

peripheral neuropathy and proximal muscle weakness

72

Vitamin C metabolic actions

hydroxylation of prolyl and lysyl residues of collagen

Converts dopamine to norepinephrine (required for enzyme dopamine beta hydroxylase)

Anti-oxidant

Facilitates iron absorption in the gut (keeps iron in reduced more easily absorbed state)

73

Scurvy/vit c deficiency

sore spongy gums
loose teeth
fragile blood vessels
swollen joints
hemarthrosis
impaired wound healing
anemia

74

What is the ddx for eosinophilia

DNAAACP

Drugs
Neoplasm
Atopic disease
Addison's disease
Acute interstitial nephritis
Collagen vascular disease
Parasites

75

What requires vitamin B1 (thiamine)

PDH

alpha-ketoglutarate dehydrageonase

transketolase

76

What are consequences of thiamine deficiency

Wernicke-Korsakoff
Dry beriberi
Wet beri beri

77

What is dry beriberi

nonspecific peripheral neuropathy with myelin degeneration
toe drop
wrist drop
foot drop
muscle weakness
hyporeflexia
areflexia

78

what is wet beriberi

Peripheral vasodilation
High output heart failure
Peripheral edema
Cardiomegaly

79

B2 (riboflavin) deficiency symptoms

Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth)
Corneal vascularization

80

B3 (niacin) deficiency symptoms

glossitis

Pellagra
Diarrhea
Dementia
Dermatitis

81

causes of niacin deficiency

Hartnup disease (decrease tryptophan absorption)

Malignant carcinoid syndrome (increase tryptophan metabolism)

INH (inhibits B6 and B3)

82

What can Niacin be used to treat

dyslipidemia, b/c increase HDL and decrease LDL.

83

Side effect of taking niacin?

Flushing rxn, which you can take aspirin 30 minutes prior

84

What is B5 used for

component of coenzyme A, transfer of acyl groups

85

Deficiency in B5

dermatitis
enteritis
alopecia
adrenal insufficiency

86

metabolic fxn of B6

(Pyridoxal phosphate) coenzyme for numerous enzymes, transaminations, deaminations.

converting AA precursors into...

heme niacin histamine gaba dopamine NE EPI

87

B6 deficiency

similar to riboflavin (angular cheilosis, glossitis)

unique is convulsions and hyperirritability and peripheral neuropathy

88

What can cause deficiency in B6

INH (same as B3)

89

B7 (biotin) role

apoenzyme for carboxylation reactions

90

B7 deficiency causes

Avidin in egg whites prevents absorption

antibiotics

91

B9 (folic acid) fxn

synthesis of DNA and repair of DNA

Synthesis of purines and pyrimidines

rapid cell division and growth

92

Biologically active form of folic acid

tetrahydrofolate

93

how does b9 deficiency occur

medications
-phenytoin
-sulfonamides
-TMP
-MTX

malnutrition

Pregnancy (rapid growth of fetus)

94

B9 deficiency

Glossitis
Diarrhea
Depression
Confusion

95

DNA virus characteristics

Double stranded
Linear genomes
Icosahedral
Replicate in the nucleus

96

Exceptions to the DNA virus characteristics

what are the DNA virus characteristics

Papillomavirus/Polyomavirus/Hepadnavirus: have circular DNA

Parvovirus is ssDNA

Poxvirus is non-icosahedral

Poxvirus replicates in cytoplasm

Double stranded
Linear genomes
Icosahedral
Replicate in the nucleus

97

Live virus vaccines

Smallpox
Yellow fever
Chicken pox (varicella)
MMR
Sabine polio vaccine (oral)
Herpes zoster vaccine
Intranasal influenza
Rotavirus

98

killed virus vaccine

injectable influenza
rabies
hepatitis A
injectable Salk polio

99

Subunit vaccine

Hepatitis B
Human papillomavirus

100

Egg allergy concerns for vaccines

Yellow fever: skin test/desensitization
Influenza: if no anaphylactic egg response
MMR: no CI

101

Non-enveloped RNA virus

Calicivirus
Picornavirus
Reovirus
Hepevirus

102

Non-enveloped DNA virus

Parvovirus
Adenovirus
Papillomavirus
Polyomavirus

103

Viral reassortment, what is it

what does it

what is the consequence

among segmented genome RNA viruses, exchange genetic segments.

shown in influenza.

can have pandemics/epidemics due to significant change in surface antigens

104

Viral recombination

found in what

Genes exchanged. progeny unlike progenitors

found in DNA or RNA with DNA phase

105

Phenotypic mixing

Surface protein packaging is mixed. only works for the first generation of progeny.

106

What is the ploidy of viruses

Haploid

Except Retrovirus have 2 copies of ssRNA

107

RNA viral genomic structure normally is

exceptions

Most ssRNA

Reovirus and Rotavirus have dsRNA

108

Positive sense RNA virus

Picornavirus
Hepevirus
Calicivirus
Flavivirus
Togavirus
Coronavirus
Retrovirus

109

Negative sense RNA virus

Orthomyxovirus
Paramyxovirus
Rhabdovirus
Filovirus
Bunyavirus
Arenavirus
Reovirus (dsRNA)

110

What can infect cells just by using their naked genome?

Exceptions?

most dsDNA virus and ssRNA positive

Poxvirus and hepatitis B are exceptions

111

What is pulsus paradoxus

causes?

when Systolic BP drops by >10 mmHg with inspiration

Caused by when the lungs are hyperinflated:
-Asthma
-COPD
-Cardiac tamponade

112

what is the most common tumor of adrenal medulla in kids and what does it cause

Adrenal neuroblastoma

Does not cause episodic HTN,

can cause sustained HTN

113

What can ketoconazole mechanistically do aside from antifungal

Inhibits desmolase

Inhibits 11beta-hydroxylase

(antiandrogen and antiglucocorticoid)

114

What is ketoconazole used for aside from antifungal?

2nd line treatment for advanced prostate cancer and for

suppresion of glucocorticoid synthesis in treating Cushing's syndrome

115

What features characterize a deficiency in 3beta-hydroxysteroid dehydrogenase

Inability to produce:
-glucocorticoids
-mineralocorticoids
-androgens
-estrogens

Excessive sodium excretion in the urine

Early death

116

What features characterize a deficiency in 17alpha-hydroxylase

Inability to produce sex hormones and cortisol-->phenotypic female who is unable to mature

Increased production of mineralocorticoids-->HTN

117

What features characterize a deficiency in 11beta-hydroxylase

Inability to produce:
-Cortisol
-Corticosterone
-Aldosterone

Increased production of deoxycorticosterone (weak mineralocorticoid)--> HTN

Increased production of sex hormones-->

118

What features characterize a deficiency in 21 alpha-hydroxylase

Inability to produce cortisol-->elevated ACTH

Inability to produce mineralocorticoids-->hypotension and salt wasting

Increased production of sex hormones-->masculinization

119

what patient groups must avoid fluoroquinolones

children
pregnant women
(joint and cartilage toxicity)

120

Causes of Cushing Syndrome

-Exogenous steroid use
-ACTH producing pituitary adenoma (cushing disease)
-Ectopic ACTH production (small cell lung cancer)
-Cortisol producing adrenal adenoma

121

Glucocorticoid toxicity symptoms

BAM, CUSHINGOID

buffalo hump
amenorrhea
moon facies
crazy
ulcers
skin changes
hypertension
infection
necrosis of femoral head
glaucoma (and cataracts)
osteoporosis
immunosuppression
diabetes

122

what is glucocorticoids antiinflammatory response from (mechanism)

Inhibits cyclooxygenase and phospholipase A2

123

What does cortisol do

Maintains BP (upregulate alpha1 arteriole receptors)

Increase gluconeogenesis

Increase lipolysis

Increase proteolysis

Suppresses immune system

Suppresses inflammation

124

why use dexamethasone for testing cause for excess cortisol?

dexamethasone test, this works b/c does not interfere with the cortisol assay

125

Most common causes of cushing syndrome

Exogenouse steroid use
Ectopic ACTH secretion
ACTH secreting pituitary adenoma
Adrenal tumor that secretes cortisol

126

what is treatment for nephrogenic diabetes insipidus and how do these treatments work

Hydrochlorothiazide-help concentrate urine

Amiloride-treats nephrogenic diabetes insipidus caused by lithium toxicity (by closing ENac channels that lithium comes in through)

Indomethacin-reduce renal blood flow

127

how do acidosis and alkalosis affect extracellular potassium concentrations

why does this occur

Acidosis is higher extracellular K+ concentration

Alkalosis is decreased extracellular K+ concentration

cells have a H+/K+ countertransport

128

Schizotypal

personality disorder with interpersonal awkwardness, odd thoughts, odd appearance, strange behavior

129

Schizophrenia

delusions or hallucinations with or without negative symptoms

Greater than 6 months

130

schizoaffective disorder

schizophrenia symptoms with mood disorder

131

schizoid

personality disorder with voluntary social withdrawal

132

schizophreniform

schizophrenia symptoms that last more than 1 month but fewer than 6 months

133

What are causes of secondary hyperaldosteronism

Renal artery stenosis
Congestive heart failure
Low protein states (cirrhosis or nephrotic syndrome)

134

what is pheochromocytoma associated with

MEN 2A and 2B
Neurofibromatosis I
EPO->polycythemia

135

What tumors can secrete erythropoietin

Pheochromocytoma
Renal cell carcinoma
Hemangioblastoma
Hepatocellular carcinoma

136

treatment for pheochromocytoma

First alpha blocker (phenoxybenzamine)

Second, beta blocker for reflex tachycardia.

Third, surgical resection

DO NOT DO BETA BLOCKER FIRST BECAUSE THIS CAN RAISE BP HIGHER.

137

Adrenal neuroblastoma is what

tumor of sympathetic ganglion cells

most common tumor of adrenal medulla in children.

138

What does adrenal neuroblastoma cause

how can you dx?

not episodes as pheochromocytoma, but causes mild HTN

Monitor HVA and VMA for diagnosis

139

Associations with adrenal neuroblastoma?

N-myc oncogene
Bombesin tumor mark
Neurofilament stain
Homer wright pseudorosettes

140

What does MEN 1 cause

-Parathyroid adenoma
-Pituitary adenoma
-Pancreatic tumor (leading to..
Gastrinoma
Insulinoma
Glucagonoma
VIPoma)

141

What does MEN2A cause

-Medullary thyroid cancer
-Pheochromocytoma
-Parathyroid hyperplasia (not adenoma as in MEN1, all the glands are a problem not just the one)

142

What does MEN2B cause

-Medullary thyroid cancer
-Pheochromocytoma
-Oral and intestinal ganglioneuromatosis (mucosal neuromas)

143

What gene is associated with MEN2A and MEN2B

RET oncogene

144

Presentation of Addison disease

Hypotension
Hyponatremia
Hyperkalemia
Weakness
Malaise
Anorexia
Weight loss
Skin hyperpigmentation

145

Cause of Addison disease

Autoimmune destruction of adrenal glands leading to decreased production of aldosterone and cortisol

146

MEN1
MEN2A
MEN2B

what tumor locations are associated with these 3 different types of multiple endocrine neoplasia

Parathyroid
Pituitary
Pancreas

Parathyroid
Pheochromocytoma
Medullary thyroid cancer

Pheochromocytoma
Medullary thyroid cancer
Mucosal neuroma

147

What would a lab detect in the plasma and urine of a patient with pheochromocytoma?

plasma
-metanephrine
-normetanephrine

urine
-VMa (vanillylmandelic acid)

148

Most common tumor of the adrenal

benign, non-functioning adrenal adenoma

149

Most common cause of primary aldosteronism

Adrenal adenoma (conn syndrome)

150

Conn syndrome presentation

(hyperaldosteronism)

-HTN
-Hypokalemia
-Metabolic alkalosis

151

why does primary hyperaldosteronism cause metabolic alkalosis

1. Decreased potassium leads to urinary H+ loss
2. As potassium goes down, cells try to pump potassium out and inherently H+ in via the cotransport

152

Stages of behavioral change

I. Precontemplation
II. Contemplation
III. Preparation
IV. Action
V. Maintenance

153

What is the characteristic sequence of the promoter region

-25: TATA box (Hogness box)
-75: CAAT

154

What does a mutation in the promoter region cause

decrease in transcription of gene

155

Which causes of vaginal discharge/vaginitis will the pH be high?

In which will the pH be low?

Low pH (normal)
-Physiologic discharge
-Candida

High pH:
-Bacterial vaginosis (Gardnerella, mobiluncus)
-Trichomonas

156

mechanism of PTU

Clinical use

SE

inhibits both peroxidase and 5' deiodinase

Preferred for pregnant women in first trimester

SE: Agranulocytosis, liver dysfunction

157

mechanism of Methimazole

Clinical use

SE

inhibits peroxidase only (not 5'-deiodinase)

Preferred in general (and 2/3rd trimester in preg)

SE: Agranulocytosis, fetal aplasia cutis (Scalp defect)

158

function of thyroid hormone

Bone growth (synergism with GH)

Increase Beta 1 receptors in heart

Increase BMR (via increase Na/K ATPase activity)

Glycogenolysis/gluconeogenesis/lipolysis

159

What is Graves' disease associated with

HLA-DR3 and HLA-B8

4:1 female predominance

160

Toxic multinodular goiter, what is it, MOA

Focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in TSH receptor

161

Jod-Basedow phenomenon

Tyrotoxicosis if a pt with iodine deficiency goiter is made iodine replete

162

Subacute thyroiditis (de Quervain)

Findings

Associated with?

self limited hypothyroidism often following a flu-like illness. May be hyperthyroid early in course

Findings:
increased ESR, jaw pain, early inflammation, very tender thyroid (Quervain is assoc with pain)

Assoc:
HLA-B35, with female predominance
Viral infections

163

Treatment of thyroid storm

Beta blocker
PTU or methimazole
Prednisolone

164

what is hashimotos assoc with

HLA-DR5 and HLA-B5

165

Most common cause of hypothyroidism

Hashimotos thyroiditis (autimmune, antithyroid peroxidase, anitthyroglobulin antibodies)

166

Risk of hashimotos

increased risk of non hodgkin lymphoma

167

Presentation of hashimoto thyroiditis

may be euthyroid or hyperthyroid early in course due to thyrotoxicosis during follicular rupture

Histo: Hurthle cells, lymphoid aggregate with germinal centers

Moderately enlarged nontender thyroid

168

subacute thyroiditis (de quervain) vs. hashimoto thyroiditis

Subacute thyroiditis is granulomatous infiltration vs. Hashomoto's lymphocytic inflammation

Subacute is PAINFUL goiter, hashmoto is PAINLESS goiter

169

Riedel's thyroiditis
how does it present

histo?

complication?

proposed mechanism?

fixed, hard, rock-like painless goiter. Similar to Undifferentiated/anaplastic carcinoma (but that is seen in older people)

HIsto:
Fibrosis
macrophages
Eosinophils

complicated by fibrosis extending to local structures (airway) mimicking anaplastif carcinoma

IgG4-related systemic disease

170

medical causes of hypothyroidism

-Amiodarone
-Tyrosine kinase inhibitors
-Lithium

171

what types of thyroid cancer are there

papillary carcinoma
follicular carcinoma
medullary carcinoma
undifferentiated/anaplastic carcinoma
lymphoma

172

Papillary carcinoma of thyroid
occurence/prognosis

Histo findings?

Risk factors?

Most common, with excellent prognosis

Empty appearing nuclei (Orphan annie eyes), Psamomma bodies, nuclear grooves,

increased risk with:
RET and BRAF mutations, or NTRK1,
Radiation and Tobacco

[activation of tyrosine kinase receptor]

173

Follicular carcinoma of thyroid
Occurance/prognosis

Histo

Complication

risk factors

2nd most common, prognosis okay

uniform cuboidal cells lining follicles, invades thyroid capsule (unlike follicular adenoma),

Can spread hematogenously

Risk:
-RAS mutation
-PAX8-PPAR gamma1 rearrangement

174

Medullary carcinoma of thyroid

Histo?

Association?

Tx?

From parafollicular C cells, produces calcitonin

Sheets of cells in an amyloid stroma

Assoc with MEN2A and MEN2B (RET mutations)

[activation of tyrosine kinase receptor]

Tx: No response to radioactive treatment, so only surgery

175

Undifferentiated/anaplastic carcinoma of thyroid

Poor prognosis, found in older patients. Similar to Riedel ( except that is in younger pt.)

Invades local structures

176

Lymphoma of thyroid

assoc w/ hashmoto thyroiditis

177

Surgical complications for thyroid removal

Parathyroid damage/removal
-Hypocalcemia

Dmg to recurrent laryngeal nerves
-hoarseness

178

What rises in hypothyroidism

LDL
Total cholesterol

179

What are the causes of hypertrophic cardiomyopathy

most familial autosomal dominant (beta-myosin heavy-chain mutation)

Friedreich ataxia

180

Causes for dilated cardiomyopathy

ABCCCD
alcohol abuse
wet Berberi
Coxsackie B virus myocarditis
Cocaine use
Chagas disease
Doxorubicin toxicity
Hemochromatosis and peripartum cardiomyopathy

181

causes of restrictive cardiomyopathy

Sarcoidosis
Amyloidosis
Postradiation fibrosis
Endocardial fibroelastosis (thick fibroelastic tissue in endocardium of young children)
Loffler syndrome (endomyocardial fibrosis with prominent eosinophilic infiltrate)
Hemochromatosis (dilated cardiomyopathy may also occur)

182

What is the biochemical pathway of sorbitol?

Glucose to Sorbitol to Fructose

Enzymes are
Aldose reductase
Sorbitol dehydrogenase

183

What tissues have aldose reductase but do not have sorbitol dehydrogenase (leading to sorbitol trapping)

Schwann cells
Lens
Retina
Kidney

184

Diabetic ketoacidosis vs. HHS

DKA:
-Ketosis
-No serum hyperosmolarity
-Hyperglycemia (>300)

HHS:
-No ketosis
-Serum hyperosmolarity
-Extreme hyperglycemia (>800)

185

for Type II diabetes, what are the drug medication classes useful

Biguanides
Sulfonylureas
Thiazolidinediones
DPP-4 inhibitors
GLP-1 agonists
Others

186

Biguanides (Metformin)

Other uses

Effects

SE

Effective, low risk for hypoglycemia, no wt gain, low cost, few SE. can be used in patients without pancreatic fxn.

Other uses:
prediabetes and PCOS

Effects:
-Decrease gluconeogenesis in the liver
-Decrease LDL
-Decrease triglycerides
-increase glycolysis
-increase peripheral glucose uptake (insulin sensitivity)

SE:
-GI upset
-Lactic acidosis (CI in renal failure)

187

Sulfonylureas
Mech

Examples

SE

Close K+ channel in beta-cell membrane so cell depolarizes resulting in insulin release. REQUIRES PANCREATIC FXN

Glimepriride/Glipizide/Glyburide (more problems with hypoglycemia, so not used much)

SE: Hypoglycemia and wt gain

188

Thiazolidinediones action

mechanism, resulting in...

SE

Risks

increased sensitivity to insulin in the peripheral tissue

Mech: binds to PPAR-gamma receptor, results in
-regulates fatty acid storage
-regulates glucose metabolism

SE:
-Weight gain,
-Edema,
-Hepatotoxicity,
-Heart failure

Risks:
-Risk of MI (Rosglitazone)
-Risk of bladder cancer and osteoporosis (Pioglitazone)

189

DPP-4 inhibitors
Examples

General description

Mech

Sitagliptin/Alogliptin/Saxagliptin/Linagliptin

Low risk of SE, hypoglycemia, and is wt neutral. But not as effective.

Prevent's DPP-4s inactivation of GLP-1

190

GLP-1 analogs examples

Mech

SE:

CI:

Exenatide/Liraglutide

Mimic incretins, decreasing glucagon secretion and increasing insulin secretion, delayed gastric emptying

SE: increased risk for acute pancreatitis, nausea

CI: insulin use

191

Amylin analogs examples

Mech

Use

SE

Pramlintide

Decreases glucagon secretion and gastric emptying

USE: only in patients taking insulin, but either Type 1 and Type 2 DM

SE: hypoglycemia, nausea, diarrhea

192

alpha-glucosidase inhibitors
examples

Mech

SE:

Acarbose/Miglitol

Inhibits intestinal brush border alpha glucosidases-->delayed sugar hydrolysis and glucose absorption leading to decrease in postprandial hyperglycemia

SE: GI disturbances

193

standard Treatment for DKA

IV fluids
IV insulin
Potassium replacement

194

standard Treatment for DM type I

Insulin

195

standard Treatment for DM type II

Low carb diet, wt loss, oral hypoglycemic agents, insulin

196

type 2 dm drug with lactic acidosis as rare but worrisome side effect

Metformin

197

type 2 dm drug with hypoglycemia as most common SE

Sulfonylureas

198

type 2 dm drug with recommended first line treatment for most patients

Metformin

199

type 2 dm drug with Not safe in settings of hepatic dysfunction or CHF

TZD (Thiazolidinediones)

200

type 2 dm drug with should not be used in patients with elevated serum creatinine

Metformin

201

type 2 dm drug with Should not be used in pt with cirrhosis or inflammatory bowel disease

alpha-glucosidase inhibitors

202

type 2 dm drug with not associated with wt gain

Metformin

203

type 2 dm drug with metabolized by liver, excellent choice in pt with renal disase

TZDs

204

type 2 dm drug with MOA closing potassium channel on beta cells, epolarization, ca influx, insulin release

Sulfonylureas

205

type 2 dm drug with MOA inhibits alphaglucosidase at intestinal brush border

Alphaglucosidase inhibitors (acarbose/Miglitol)

206

type 2 dm drug with MOA agonist at PPARgamma receptors leading to improved target cell response to insulin

TZDs

207

type 2 dm drug with MOA decreasing hepatic gluconeogenesis

Metformin

208

type 2 dm drug with good for wt loss

GLP-agonists

209

type 2 dm drug with Avoid in hypoglycemia

sulfonylureas

210

type 2 dm drug with Best treatment for anyone with organ failure

Insulin

211

Pt with normally well controlled type I diabetes but gets DKA. what is the diff dx?

infection
dehydration
nonadherence to insulin
severe medical illness (MI or trauma)
steroids
alcohol or drug abuse

212

Leptin action

Inhibits Lateral hypothalamus
Stimulates ventromedial nuclei

Both reslut in satiety

213

What is seen in kwashiokor

skin lesions
edema
liver function

214

what is seen in marasmus

tissue and muscle wasting
loss of subcutaneous fat

215

what vitamins should vegetarians supplement in their diet

vitamin B12

216

Anti-GBM antibodies (IF)

Goodpasture syndrome

217

Kimmelstiel-Wilson lesions

Diabetic nephropathy

218

Spike and dome appearance

Membranous glomerulonephritis

219

Tram track appearance of subendothelial humps

Membranoproliferative glomerulonephritis

220

subepithelial humps

Acute poststreptococcal glomerulonephritis

221

RLE of heme synthesis and its required cofactor

aminolevulinic acid synthase

Vit B6 is required cofactor

222

What makes aminolevulinic aci

glycine and succinyl CoA

223

Acute intermittent porphyria, what causes it

how does it present

tx

deficiency in porphobilinogen deaminase (uruporphyrinogen 1 synthase)

presents as the 5 P's
-painful abdomen
-port wine urine
-polyneuropathy
-psychological disturbances
-precipitated by drugs (barbiturates, seizure drugs, rifampin, metoclopramide)

tx: glucose and heme, which inhibits the ALA synthase

224

Porphyria cutanea tarda

cause

presentation

associations

most common form of porphyria

deficiency in uroporphyrinogen decarboxylase

presents:
-blistering of the skin
-tea colored urine
-hypertrichosis
-facial hyperpigmentation

assoc with:
Hepatitis C
Alcoholism
Elevations of your LFTs

225

How does lead poisoning effect heme synthesis?

presentation

Tx

-ALA dehydratase
-Ferrochelatase (leading to increased levels of protoporphyrin in RBC)

presents:
microcytic anemia, GI and kidney disease
Children:exposure to lead paint leading to mental deterioration
Adult: environmental exposure leading to headache/memory loss/deyelination
Encephalopathy/Memory loss and delirium and mental deterioration/Foot drop or wrist drop
lead lines in gingevae (burton lines)
sideroblastic anemia in BM
Basophilic stippling in RBC
abdominal colic
renal failure

tx:
EDTA or succimer in either kids or adults
Dimercaprol and succimer for severe in kids

226

What tumors can increase EPO?

Potentially Really High Hematocrit

Pheochromocytoma
Renal cell carcinoma
Hepatocellular carcinoma
Hemangioblastoma

*trisomy 21 at birth

227

Where does fetal erythropoesis occur?

yolk sac 3-8 wks
liver and spleen
bone marrow after 28 weeks

228

in which adult bones does erythropoiesis take place?

Vertebrae, ribs, pelvis

229

what substrate and cofactor for generating GABA

Glutamate and B6

230

what can iron deficiency manifest as

Plummer-Vinson syndrome:
Iron deficiency anemia
Esophageal webs
Atrophic glossitis

231

how do you distinguish folate from B12 deficiency in megaloblastic anemia

B12 has neurologic deficits (peripheral neuropathy/dementia)

Folate deficiency, MethylMalonicAcid will be normal (b12 will be increased)

232

Causes of macrocytic nonmegaloblastic anemia

Liver disease
Alcoholism
Reticulocytosis leading to increased MCV
Drugs:
-5-FU
-Zidovudine
-Hydroxyurea

233

Causes of normocytic nonhemolytic anemia

Anemia of chronic diseas e(can go to microcytic)
Aplastic anemia
CKD

234

women develops intense muscle cramps and darkening of her urine after exercise.

McArdle disease

235

Immune thrombocytopenia (ITP)

antibodies bind to 2b/3a on the surface of platets-->immune system removes and destroys those platelets

Plateet count is low

Increased megakaryocytes on BM biopsy

tx:Steroids, IVIG, Splenectomy

236

Thrombotic thrombocytopenic purpura (TTP)

Widespread platelet thrombosis, thrombocytopenia because used up

Bleeding and purpura

Deficiency in metalloprotease ADAMTs13, normally cleaves vWF multimers into smaller active vWF units.excessive platelet activation and aggregation.

237

HUS-hemolytic uremic syndrome

associated with

classic triad, milder form of TTP
-hemolysis
-renal insufficiency
-thrombocytopenia

associated with E. coli 0157:H7 infectino

238

TTP pentad

FAT RN
or
Nasty Fever Torched His Kidneys

-hemolysis
-renal insufficiency
-thrombocytopenia
-neurological symptoms
-fever

239

von Willebrand disease

tx:

defect of vWF so...
-Increase in PTT (normally stabilizes and protects factor VIII)
-Prolonged bleeding time (Binds to subendothelial collagen and to glcyoprotein 1b)

tx:
DDAVP, desmopressin, which increases the release of vWF from endothelial cells

240

DIC, disseminated intravascular coagulation

Widespread activation of clotting, consuming all platelets and coagulation factor

results
-prolonged bleeding time
-increased PT and PTT
-low fibrinogen
-High D-dimer (fibrin split products)
-Schistocytes
-Bleeding
-Multi-organ failure

241

DIC causes

STOP Making Thrombi

Sepsis
Trauma
Obstetric complications
Acute Pancreatitis
Malignancy
Transfusion

242

fructose intolerance enzyme deficiency

aldolase b

243

essential fructosuria enzyme deficiency

fructokinase

244

classic galactosemia deficiency

galactose-1-phosphate uridyltransferase

245

Wiskott Aldrich

WAITER
-Wiskott
-Aldrich
-Immunodeficiency
-Thrombocytopenia and purpura
-Eczema
-Recurrent pyogenic infections

246

Hemosidinuria and thrombosis

PNH, paroxysmal nocturnal hemoglobinuria

247

Leukemia vs. lymphoma

Leukemia is in bone marrow or may spill into peripheral blood

Lymphoma is in lymph node

248

what is Marginal cell MALToma associated with

Sjogren syndrome
Hashimoto thyroiditis
H. pylori

249

most common type of non Hodgkin lymphoma in adults?

In children

adults: diffuse large B cell lymphoma

Children: lymphoblastic lymphoma

250

How does multiple myeloma present

anemia
renal insufficiency
back pain
hypercalcemia

251

Most common leukemia in children

ALL

252

most common leukemia in adults in US

CLL

253

Myelodysplastic syndromes have a tendence to progress to

AML

254

Myeloproliferative disorders may progress to

AML

255

Numerous basophils, splenomegaly, negative for leukocyte alkaline phosphatase (LAP)

CML