Endocrine and Biochemistry Flashcards
Mechanism of potassium iodide =
Competitively inhibits the uptake of radioactive iodine into follicular cells. Increased iodine also decreases release of T4/T3 due to the Wolff Chaikoff Effect.
Function of smooth ER = (3)
- produces steroids and phospholipids (contains the appropriate enzymes)
- acts as the sarcoplasmic reticulum for striated muscles
- detoxification of drugs
What medication can be given to men who are suffering from gynecomastia?
SERM - inhibits ER in breast tissue
Hypoketotic hypoglycemia in a young kid after a long period of fasting is most likely a deficiency in _
FA beta-oxidation
Most likely it is inhibition of acyl CoA dehydrogenase enzyme.
Will not be able to oxidize FA for energy and cannot produce ketone bodies
Superior thyroid artery and vein travel with _ nerve
external branch of the superior laryngeal nerve
-innervates the cricothyroid muscle
Inferior thyroid artery and vein travel with _ nerve
recurrent laryngeal nerve
Gene from Albright Hereditary Osteodystrophy is inherited from mother/father
mother - due to imprinting of father’s genes
AD
defective Gs alpha subunit in the PTH receptor = pseudohypoparathyroidism - end organ resistance to PTH
presentation:
- serum= low Ca, high P, high PTH
- shortened 4th/5th digits
- short stature
Conn syndrome =
Primary adrenal adenoma
increased aldo
decreased renin
Addison’s disease =
Primary adrenal insufficiency
decreased aldo
decreased cortisol
Metyrapone stimulation test
Blocks the last step of cortisol synthesis (11DOC -> cortisol)
Helps dx adrenal insufficiency
11-beta hydroxylase deficiency findings
female genitalia =
- decreased aldo
- increased 11-DOC (not salt wasting)
- increased BP
- decreased renin
- increased androstenedione
female genitalia are ambiguous (due to increased androstenedione)
21 hydroxylase deficiency findings
female genitalia =
male genitalia =
- decreased aldo (salt wasting)
- decreased BP
- increased renin
- increased 17-hydroxyprogesterone
- increased androstenedione
female genitalia are ambiguous (due to increased androstenedione)
male genitalia is normal and they are identified later due to salt wasting
17-alpha hydroxylase deficiency findings
female vs male genitalia
- increased aldo (not salt wasting)
- increased BP
- decreased androstenedione
females - born with normal genitalia but will not have secondary sex characteristics
males - born undervirilized or with female external genital (due to decreased androstenedione)
Insulin independent glucose uptake locations (6)
- Brain
- RBC
- Intestine
- Cornea
- Kidney
- Liver
MEN 1
- Pituitary adenoma (prolactin or GH)
- Pancreas endocrine tumor (Zollinger-Ellison (gastrinoma), Insulinoma, VIPoma, Glucagonoma)
- Parathyroid adenomas
mutation in MEN1 gene - menin tumor suppressor protein
MEN2A
- Parathyroid hyperplasia
- Thyroid medullary carcinoma (C cell tumor - secrete calcitonin)
- Pheochromocytoma
mutation in RET gene - receptor tyrosine kinase
affects cells of neural crest origin!
MEN2B
- Thyroid medullary carcinoma (C cell tumor - secretes calcitonin)
- Pheochromocytoma
- Muosal neuroma (oral/intestinal ganglioneuromatosis)
mutation in RET gene - receptor tyrosine kinase
associated with marfanoid habitus
Hashimoto thyroiditis associated HLA subtype =
HLA-DR5, DR3
Diabetes Mellitus Type 1 associated HLA subtype =
HLA-DR4
HLA-DR3
Vitamin _ deficiency -> hemolytic anemia, acanthocytosis, posterior column or spinocerebellar tract demyelination
Vitamin E deficiency
Niacin is derived from _ and requires what two cofactors?
Derived from tryptophan
Cofactors = B2 (riboflavin), B6 (pyridoxine)
Niacin is B3
Requires B2, B6
(6/2=3)
Elfin facies + intellectual disability with well developed verbal skills + hypercalcemia =
Williams Syndrome - microdeletion of long arm Chr 7 (includes elastin gene)
Hypercalcemia is due to increased vitamin D sensitivity
Myotnia + Cataracts + Testicular atrophy + CTG repeat =
myotonic dystropy type 1
mutation in the DMPK gene -> abnormal myotonin protein kinase
Cancers associated with Li Fraumeni Syndrome (4)
- Sarcoma
- Breast
- Leukemia
- Adrenal gland
Cross linking of elastin is done by _ enzyme
lysyl oxidase with copper cofactor required
this is the same enzyme that crosslinks collagen fibrils
Mutation in ATP7A + brittle, kinky hair + growth retardation =
Menke disease
-decreased copper absorption which leads to a decreased collagen and elastin synthesis
Coarse facial features + clouded corneas + limited joint movements + increased plasma lysosomal enzymes + child
I cell disease - inhibits N-acetylglycosaminyl-1-phosphotransferase enzyme
Results in the failure of the golgi to add a mannose-6-phosphate to glycoproteins that are supposed to be degraded in the lysosome
Ribosomes: prokaryotic vs eukaryotic
- 80s
- 70s
- 80s = 40s+60s -> eukaryotes
- 70s = 30s+50s -> prokaryotes
eukaryotes - even numbers
prokaryotes - odd numbers
tRNA thymine + pseudouracil + cytosine sequence is used for
tRNA-ribosome binding
tRNA dihydrouracil residue is used for
tRNA recognition of the correct aminoacyl tRNA synthetase
anti-spliceosome snRNP antibody =
anti-Smith antibody = SLE!
Lac operon requires what to function?
available lactose
glucose can be low or high but as long as lactose is available, there will be transcription of the lac operon
Histones are rich in what 2 amino acids?
- Lysine
- Arginine
Vomiting + Rice water stools + Garlic breath
Arsenic poisoning
Infant with increased serum alanine + lactic acidosis + neurological deficits =
Pyruvate Dehydrogenase Complex deficiency
- X-linked
- Treatment = ketogenic diet (high fat, low carb, high lysine and leucine)
Lysine and Leucine are ketogenic AA -generates the ketone body precursor to acetyl CoA and therefore does not go through the pyruvate pathway
Locations of HMP shunt/Pentose Phosphate Pathway (4)
- lactating mammary gland
- liver
- adrenal cortex
- RBC
Essential AA (9)
Met Val His Ile Phe Thr Trp Leu Lys
Acidic AA (2)
Asp
Glu
Basic AA (3)
Arg
Lys
His (neutral at body pH)
underlying pathology for Graves’ proptosis =
Inflammation
Steroids help decrease the ophthalmic symptoms
Main pathogenesis of T1DM =
autoimmune insulinitis - cell mediated destruction of the beta-pancreatic cells
NADPH is used in what reactions? (4)
- Reduction of glutathione (prevents oxidative damage)
- Synthesis of cholesterol
- Synthesis of FA
- Synthesis of steroids
Physical and mental retardation + megaloblastic anemia + increased orotic acid in urine
What is the treatment?
Orotic aciduria
Treatment = uridine supplementation
Painful rash on face, groin and perineum involving crusting, coalescing erythematous borders with central bronze induration.
Light microscopy shows superficial necrolysis.
Glucagonoma
Sympathetic stimulation of pancreatic beta cells =
Decreases insulin release due to the alpha-2>beta-2
alpha-2 = decreases insulin release due to Gi beta-2 = increases insulin release due to Gs
Why are non-selective beta blockers dangerous in DM patients?
Exacerbates the hypoglycemia and masks the adrenergic symptoms that hypoglycemia can cause
Thyroid biopsy - empty appearing nuclei with central clearing + nuclear grooves
Papillary thyroid carcinoma
- empty nuclei = Owl’s eyes
- also presents with psamomma bodies
Thyroid nodule that is invading the capsule and surrounding vasculature
Follicular thyroid carcinoma
note: this cannot be diagnosed via fine needle biopsy
Thyroid biopsy - lymphocytic infiltrate with well developed germinal centers and eosinophilic metaplasia of the cells surrounding the follicles
Hashimoto thyroiditis
eosinophilic metaplasia = Hurthle cells
The follicles are making the antibodies (autoimmune pathogenesis)
- anti-microsomal Ab
- anti-thyroglobulin Ab
Thyroid biopsy - granulomatous inflammation + follows a flu-like illness + painful + increased ESR
Subacute (de Quervain) thyroiditis
Young patient with a hard painless thyroid
Ridel fibrosing thyroiditis
Beriberi is a _ deficiency
Thiamine (B1)
Causes peripheral neuropathy (“dry”) or peripheral neuropathy + dilated cardiomyopathy (“wet”)
What 5 AA can be synthesized into propionyl CoA?
- Valine
- Leucine
- Isoleucine
- Methionine
- Threonine
What AA is used to make NO?
Arginine
What 2 AA are used to make urea?
Arginine
Aspartate
What AA is used to make GABA?
Glutamate
What 3 things can Tryptophan be made into?
- Serotonin
- Melatonin
- Niacin
Fetal adrenal cortex releases what steroid?
DHEA
GH release is stimulated by hyper/hypoglycemia?
Hypoglycemia
Glucose inhibits GH release
5 yo + exophthalmos + lytic bone lesions at the base of the skull + polyuria + polydipsia
Langerhans histiocytosis with Diabetes Insipidus
Mutations in follicular thyroid carcinoma? (2)
- RAS oncogene
- PAX8-PPAR gamma fusion gene
Tapping on facial nerve leading to contraction occurs in increased/decreased serum Ca?
Chvostek sign
- Indicates decreased serum Ca
- Usually due to hypoparathyroidism - low PTH, low Ca
Locations of ADH receptors
V1 - vascular smooth muscle
V2 - cortical collecting duct and vascular endothelium
GH is _ in striated muscle and _ in adipose tissue
- anabolic in striated muscle
- catabolic in adipose tissue
Maturity onset diabetes of the young/gestational diabetes is caused by a mutation in _ enzyme
Glucokinase
Underlying cause of DKA?
Lack of insulin
Renal osteodystrophy occurs with _ hyperparathyroidism
Secondary or Tertiary
- Due to an underlying renal problem -> decreased vitamin D -> decreased Ca from gut -> decreased serum Ca -> increased PTH
- Renal problem -> increased serum P because it cannot be removed properly
Subperiosteal resorption with cystic degeneration + decreased serum phosphate + increased serum calcium + increased urinary calcium =
Primary hyperparathyroidism and Osteitis fibrosa cystica
Infant, 46XY, small phallus, hypospadias, small testes palpated in the inguinal area, serum T normal, BP normal.
Defective 5-alpha reductase -> decreased DHT therefore external genitalia is not formed correctly (pseudohermaphroditism)
Does maternal insulin cross the placenta?
NO
Maternal glucose DOES cross the placenta and the fetus’ pancreatic beta cells begin to secrete their own insulin (pancreatic beta cell hyperplasia)
Prolonged ACTH stimulation of the adrenal cortex causes a of the b and c layers
a=Hyperplasia
b=Fasciculata
c=Reticularis
Cortisol - anabolic or catabolic?
Mostly catabolic except for in the live (+GNG and glycogenesis)
Opposite of insulin.
Insulin vs Glucagon - phosphorylator vs dephosphorylator
Insulin = dephosphorylator Glucagon = phosphorylator
light microscopy of the thyroid: Nests or sheets of polygonal or spindle shaped cells with extracellular amyloid deposits that stain with congo red
Medullary thyroid carcinoma
-part of MEN2A or MEN2B
Alcohol suppresses what reactions resulting hypoglycemia?
Inhibits GNG
- inhibition of alpha-KG DH and PDH enzymes due to lack of thiamine (B1)
- inhibition of all reactions that require NAD due to the fact ethanol -> acetyl CoA used it all up
- inhibition of transketolase enzymes due to lack of thiamine (B1)
Alcohol does not inhibit any enzymes in the glycogenolysis pathway. This is the main route of glucose production until hepatic glycogen stores are depleted.
Patient with increased T4, decreased radioactive iodine uptake, hyperthyroid symptoms
Ingestion of exogenous thyroxine (people do this for weight loss purposes)
The TSH level will also be decreased (which is related to the decreased radioactive iodine uptake)
TCA enzyme(s) that require niacin (3)
Niacin (B3) = NAD
- Isocitrate DH
- Alpha-ketoglutarate DH
- Malate DH
TCA enzyme that requires riboflavin
Riboflavin (B2) = FAD
-Succinate DH requires FAD to make FADH2 (this enzyme is also complex II in the ETC)
Lower leg skin thickening and induration + elevated T4 + decreased TSH =
Graves hyperthyroidsim
Grave’s disease associated HLA subtype =
HLA-DR3
Celiac disease associated HLA subtype =
HLA-DQ2 and DQ8
Excessive ingestion of raw egg whites causes _ deficiency
Biotin (B7)
-Dermatitis, alopecia, enteritis
Enzymes that require biotin: carboxylation reactions
- Pyruvate carboxylase
- Acetyl CoA carboxylase
- Propionyl CoA carboxylase
Young child, Progressive spastic diplegia (bilateral leg stiffness), Growth delay, Abnormal chorioathetoid movements, Elevate arginine levels, Normal ammonia levels
Arginase deficiency
- cannot make urea from urea cycle
- treatment: low protein diet
3 antioxidant enzymes:
- superoxide dismutase
- glutathione peroxidase
- catalase
converts ROS -> O2 + H2O
What pathway are these enzymes a part of?
- Aldose reductase
- Sorbitol dehydrogenase
Polyol pathway
-occurs in seminal vesicles, retina, lens, renal papilla, Schwann cells
glucose -(aldose reductase)-> sorbitol -(sorbitol dehydrogenase)-> fructose
Sorbitol cannot readily cross membranes so in the certain tissues, it gets stuck
-cataracts in the lens
Pancreatic ductal secretions and absorptions during high flow
Secretion: HCO3-, Na+, H2O
Absorption: Cl-
Elevated baseline/fasting insulin levels with normal glucose levels =
Insulin resistance
An insulinoma would have elevated insulin levels with hypoglycemia
