DIT Part 2 Flashcards
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
What are the main ketone bodies
Acetoacetate
Beta-hydroxybutyrate
RLS for ketone synthesis
HMG-CoA synthase (NOT REDUCTASE)
Acetoacetate sponteously becomes
Acetone
note the fruity smell to breath
Urine test for ketone bodies tests for
Tests for Acetoacetate
NOT beta-hydroxybutyrate
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
what can the body do with acetyl-CoA
TCA cycle
FA synthesis
Cholesterol synthesis
Ketone synthesis
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)
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
What are risks for hepatocellular carcinoma
Hep B and C Hemochromatosis alpha1-antitrypsin deficiency Hepatic adenoma Any type of Cirrhosis
TCA overdose symptoms
convulsions
coma
cardiotoxicity
hyperpyrexia
respiratory depression
Apo B-48
Chylomicron secretion from enterocyte to lymphatic system
ApoB-100
Found on VLDL, IDL, and LDL
Apo E
Mediates extra remnant uptake
Apo A-I
Activates LCAT, found on HDL
Apo C-II
Cofactor for lipoprotein lipase
Chlylomicron has what apoproteins
Apo E, Apo A-I, Apo C-II, Apo B-48
Chylomicron remnant has what apoproteins
Apo E, Apo B-48
VLDL has what apoproteins
Apo E, Apo C-II, Apo B-100
IDL has what apoproteins
Apo E, Apo B-100
LDL has what apoproteins
Apo B-100
HDL has what apoproteins
Apo E, Apo A-I Apo C-II
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
treatment of abetalipoproteinemia
Vitamin E
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
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)
Type IV hypertriglyceridemia
Mech:
Presentation
Autosomal dominant
Mech: Overproduction of VLDL
Pancreatitis (from increased triglycerides)
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
Fatty acid synthesis:
Precursor,Location, RLS
Acetyl-CoA is precursor, occurs in cytoplasm of hepatocytes, RLS is Acetyl-CoA carboxylase
Fatty acid degrdation:
Location
RLS
located in mitochondria, RLS is Carnitine acyltransferase-1 (aka carnitine palmitoyl transferase-1)
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.
What are the essential amino acids
Private (PVT) TIM HaLL
- Phenylalanine
- Valine
- Threonine
- Tryptophan
- Isoleucine
- Methionine
- Histidine
- Arginine
- Leucine
- Lysine
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)
Acidic AAs
Aspartate and glutamate
-negatively charged
Phenylalanine to Epi
Phenylalanine Tyrosine Dopa Dopamine NE Epi
What can arginine be turned into
Creatine
Urea
Nitric oxide
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
RLS for Heme synthesis
Aminolevulinic synthase
Urea cycle RLS
Carbamoyl phosphate synthetase- I
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
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
Symptoms of hyperammonemia
Slurring of speech Somnolence Vomiting Cerebral edema Blurring of the vision
Treating hyperammonemia
Low protein diet
If urea cycle problem:
Phenylbutyrate
Benzoate
Biotin (stimulate ornithine transcarbamylase)
PKU causes
2 ways
either missing phenylalanine hydroxylase
or
missing BH4 (tetrahydrobiopterin)
Why do you get neurotoxic effects in PKU
from high levels of phenylalanine, not due to phenylketones
what are the phenylketones
phenylacetate
phenyllactate
Phenylpyruvate
s/s of pku
growth retardation mental retardation seizures fair skin (no melanin) eczema musty body odor
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.
What happens to infant in gestational pku
phenylketones are toxic
- microcephaly
- intellectual disability
- growth retardation
- congenital heart defects
Alkaptonuria mechanism
congenital autosomal recessive and benign deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate.
s/s in alkaptonuria
dark connective tissue, brown pigmented sclerae, urine turns black on prolonged exposure to air. Debilitating arthralgias
Albinism causes
- Tyrosinase deficiency
- Defective tyrosine transport
- Abnormal neural crest migration of melanocytes
what is a consequence of albinism
skin cancer more likely
Homocystinuria causes
- Deficiency of cystathionine synthase
- Decreased affinity of the cystathionine synthase for the pyridoxal phosphate
- Deficiency of homocysteine methyltransferase
S/S homocystinuria
mental retardation, tall stature, osteoporosis kyphosis Atherosclerosis Subluxation of the lens (downward dislocation, c/f with marfans with upward dislocation
Cystinuria cause
defect of the renal tubular AA transporter for COLA (cysteine, ornithine, lysine, arginine), normally in the convoluted proximal tubule
s/s of cystinuria
tx
Cysteine kidney stones
tx: acetazolamide to prevent
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
maple syrup urine disease s/s
intellectual deficiencies
Severe CNS defects
Hartnup cause
Autosomal recessive defect of transporter in intestine and kidneys leading to deficiency of neutral AA (tryptophan)
Hartup s/s
Pellagra (vitamin B3 deficiency)
Dermatitis
Diarrhea
Dementia
Vitamin D toxicity causes
Too much vitamin D supplementation
Sarcoidosis (increase in conversion of 25-OH D3 to 1,25-OH D3)
Vitamin K deficiency causes
Medications
- Coumadin
- Anticonvulsants (phenytoin)
- Antibiotics
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
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)
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)
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
What presentation of vitamin A toxicities can be seen
livers of bears (polar bears, or otherwise)
Pregnant mothers (teratogenic)
Vitamin E other name
alpha-tocopherol
What does vitamin E do
antioxidant, prevents non-enzymatic oxidation of cell components by free radicals (especially important for RBC)
vitamin E deficiency
hemolytic anemia
spinocerebellar degeneration resulting in ataxia
peripheral neuropathy and proximal muscle weakness
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)
Scurvy/vit c deficiency
sore spongy gums loose teeth fragile blood vessels swollen joints hemarthrosis impaired wound healing anemia
What is the ddx for eosinophilia
DNAAACP
Drugs Neoplasm Atopic disease Addison's disease Acute interstitial nephritis Collagen vascular disease Parasites
What requires vitamin B1 (thiamine)
PDH
alpha-ketoglutarate dehydrageonase
transketolase
What are consequences of thiamine deficiency
Wernicke-Korsakoff
Dry beriberi
Wet beri beri
What is dry beriberi
nonspecific peripheral neuropathy with myelin degeneration toe drop wrist drop foot drop muscle weakness hyporeflexia areflexia
what is wet beriberi
Peripheral vasodilation
High output heart failure
Peripheral edema
Cardiomegaly
B2 (riboflavin) deficiency symptoms
Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth)
Corneal vascularization
B3 (niacin) deficiency symptoms
glossitis
Pellagra
Diarrhea
Dementia
Dermatitis
causes of niacin deficiency
Hartnup disease (decrease tryptophan absorption)
Malignant carcinoid syndrome (increase tryptophan metabolism)
INH (inhibits B6 and B3)
What can Niacin be used to treat
dyslipidemia, b/c increase HDL and decrease LDL.
Side effect of taking niacin?
Flushing rxn, which you can take aspirin 30 minutes prior
What is B5 used for
component of coenzyme A, transfer of acyl groups
Deficiency in B5
dermatitis
enteritis
alopecia
adrenal insufficiency
metabolic fxn of B6
(Pyridoxal phosphate) coenzyme for numerous enzymes, transaminations, deaminations.
converting AA precursors into…
heme niacin histamine gaba dopamine NE EPI
B6 deficiency
similar to riboflavin (angular cheilosis, glossitis)
unique is convulsions and hyperirritability and peripheral neuropathy
What can cause deficiency in B6
INH (same as B3)
B7 (biotin) role
apoenzyme for carboxylation reactions
B7 deficiency causes
Avidin in egg whites prevents absorption
antibiotics
B9 (folic acid) fxn
synthesis of DNA and repair of DNA
Synthesis of purines and pyrimidines
rapid cell division and growth
Biologically active form of folic acid
tetrahydrofolate
how does b9 deficiency occur
medications
- phenytoin
- sulfonamides
- TMP
- MTX
malnutrition
Pregnancy (rapid growth of fetus)
B9 deficiency
Glossitis
Diarrhea
Depression
Confusion
DNA virus characteristics
Double stranded
Linear genomes
Icosahedral
Replicate in the nucleus
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
Live virus vaccines
Smallpox Yellow fever Chicken pox (varicella) MMR Sabine polio vaccine (oral) Herpes zoster vaccine Intranasal influenza Rotavirus
killed virus vaccine
injectable influenza
rabies
hepatitis A
injectable Salk polio
Subunit vaccine
Hepatitis B
Human papillomavirus
Egg allergy concerns for vaccines
Yellow fever: skin test/desensitization
Influenza: if no anaphylactic egg response
MMR: no CI
Non-enveloped RNA virus
Calicivirus
Picornavirus
Reovirus
Hepevirus
Non-enveloped DNA virus
Parvovirus
Adenovirus
Papillomavirus
Polyomavirus
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
Viral recombination
found in what
Genes exchanged. progeny unlike progenitors
found in DNA or RNA with DNA phase
Phenotypic mixing
Surface protein packaging is mixed. only works for the first generation of progeny.
What is the ploidy of viruses
Haploid
Except Retrovirus have 2 copies of ssRNA
RNA viral genomic structure normally is
exceptions
Most ssRNA
Reovirus and Rotavirus have dsRNA
Positive sense RNA virus
Picornavirus Hepevirus Calicivirus Flavivirus Togavirus Coronavirus Retrovirus
Negative sense RNA virus
Orthomyxovirus Paramyxovirus Rhabdovirus Filovirus Bunyavirus Arenavirus Reovirus (dsRNA)
What can infect cells just by using their naked genome?
Exceptions?
most dsDNA virus and ssRNA positive
Poxvirus and hepatitis B are exceptions
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
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
What can ketoconazole mechanistically do aside from antifungal
Inhibits desmolase
Inhibits 11beta-hydroxylase
(antiandrogen and antiglucocorticoid)
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
What features characterize a deficiency in 3beta-hydroxysteroid dehydrogenase
Inability to produce:
- glucocorticoids
- mineralocorticoids
- androgens
- estrogens
Excessive sodium excretion in the urine
Early death
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
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–>
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
what patient groups must avoid fluoroquinolones
children
pregnant women
(joint and cartilage toxicity)
Causes of Cushing Syndrome
- Exogenous steroid use
- ACTH producing pituitary adenoma (cushing disease)
- Ectopic ACTH production (small cell lung cancer)
- Cortisol producing adrenal adenoma
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
what is glucocorticoids antiinflammatory response from (mechanism)
Inhibits cyclooxygenase and phospholipase A2
What does cortisol do
Maintains BP (upregulate alpha1 arteriole receptors)
Increase gluconeogenesis
Increase lipolysis
Increase proteolysis
Suppresses immune system
Suppresses inflammation
why use dexamethasone for testing cause for excess cortisol?
dexamethasone test, this works b/c does not interfere with the cortisol assay
Most common causes of cushing syndrome
Exogenouse steroid use
Ectopic ACTH secretion
ACTH secreting pituitary adenoma
Adrenal tumor that secretes cortisol
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
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
Schizotypal
personality disorder with interpersonal awkwardness, odd thoughts, odd appearance, strange behavior
Schizophrenia
delusions or hallucinations with or without negative symptoms
Greater than 6 months
schizoaffective disorder
schizophrenia symptoms with mood disorder
schizoid
personality disorder with voluntary social withdrawal
schizophreniform
schizophrenia symptoms that last more than 1 month but fewer than 6 months
What are causes of secondary hyperaldosteronism
Renal artery stenosis
Congestive heart failure
Low protein states (cirrhosis or nephrotic syndrome)
what is pheochromocytoma associated with
MEN 2A and 2B
Neurofibromatosis I
EPO->polycythemia
What tumors can secrete erythropoietin
Pheochromocytoma
Renal cell carcinoma
Hemangioblastoma
Hepatocellular carcinoma
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.
Adrenal neuroblastoma is what
tumor of sympathetic ganglion cells
most common tumor of adrenal medulla in children.
What does adrenal neuroblastoma cause
how can you dx?
not episodes as pheochromocytoma, but causes mild HTN
Monitor HVA and VMA for diagnosis
Associations with adrenal neuroblastoma?
N-myc oncogene
Bombesin tumor mark
Neurofilament stain
Homer wright pseudorosettes
What does MEN 1 cause
-Parathyroid adenoma
-Pituitary adenoma
-Pancreatic tumor (leading to..
Gastrinoma
Insulinoma
Glucagonoma
VIPoma)
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)
What does MEN2B cause
- Medullary thyroid cancer
- Pheochromocytoma
- Oral and intestinal ganglioneuromatosis (mucosal neuromas)
What gene is associated with MEN2A and MEN2B
RET oncogene
Presentation of Addison disease
Hypotension Hyponatremia Hyperkalemia Weakness Malaise Anorexia Weight loss Skin hyperpigmentation
Cause of Addison disease
Autoimmune destruction of adrenal glands leading to decreased production of aldosterone and cortisol
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
What would a lab detect in the plasma and urine of a patient with pheochromocytoma?
plasma
- metanephrine
- normetanephrine
urine
-VMa (vanillylmandelic acid)
Most common tumor of the adrenal
benign, non-functioning adrenal adenoma
Most common cause of primary aldosteronism
Adrenal adenoma (conn syndrome)
Conn syndrome presentation
(hyperaldosteronism)
- HTN
- Hypokalemia
- Metabolic alkalosis
why does primary hyperaldosteronism cause metabolic alkalosis
- 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
Stages of behavioral change
I. Precontemplation II. Contemplation III. Preparation IV. Action V. Maintenance
What is the characteristic sequence of the promoter region
- 25: TATA box (Hogness box)
- 75: CAAT
What does a mutation in the promoter region cause
decrease in transcription of gene
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
mechanism of PTU
Clinical use
SE
inhibits both peroxidase and 5’ deiodinase
Preferred for pregnant women in first trimester
SE: Agranulocytosis, liver dysfunction
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)
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
What is Graves’ disease associated with
HLA-DR3 and HLA-B8
4:1 female predominance
Toxic multinodular goiter, what is it, MOA
Focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in TSH receptor
Jod-Basedow phenomenon
Tyrotoxicosis if a pt with iodine deficiency goiter is made iodine replete
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
Treatment of thyroid storm
Beta blocker
PTU or methimazole
Prednisolone
what is hashimotos assoc with
HLA-DR5 and HLA-B5
Most common cause of hypothyroidism
Hashimotos thyroiditis (autimmune, antithyroid peroxidase, anitthyroglobulin antibodies)
Risk of hashimotos
increased risk of non hodgkin lymphoma
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
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
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
medical causes of hypothyroidism
- Amiodarone
- Tyrosine kinase inhibitors
- Lithium
what types of thyroid cancer are there
papillary carcinoma follicular carcinoma medullary carcinoma undifferentiated/anaplastic carcinoma lymphoma
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]
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
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
Undifferentiated/anaplastic carcinoma of thyroid
Poor prognosis, found in older patients. Similar to Riedel ( except that is in younger pt.)
Invades local structures
Lymphoma of thyroid
assoc w/ hashmoto thyroiditis
Surgical complications for thyroid removal
Parathyroid damage/removal
-Hypocalcemia
Dmg to recurrent laryngeal nerves
-hoarseness
What rises in hypothyroidism
LDL
Total cholesterol
What are the causes of hypertrophic cardiomyopathy
most familial autosomal dominant (beta-myosin heavy-chain mutation)
Friedreich ataxia
Causes for dilated cardiomyopathy
ABCCCD alcohol abuse wet Berberi Coxsackie B virus myocarditis Cocaine use Chagas disease Doxorubicin toxicity Hemochromatosis and peripartum cardiomyopathy
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)
What is the biochemical pathway of sorbitol?
Glucose to Sorbitol to Fructose
Enzymes are
Aldose reductase
Sorbitol dehydrogenase
What tissues have aldose reductase but do not have sorbitol dehydrogenase (leading to sorbitol trapping)
Schwann cells
Lens
Retina
Kidney
Diabetic ketoacidosis vs. HHS
DKA:
- Ketosis
- No serum hyperosmolarity
- Hyperglycemia (>300)
HHS:
- No ketosis
- Serum hyperosmolarity
- Extreme hyperglycemia (>800)
for Type II diabetes, what are the drug medication classes useful
Biguanides Sulfonylureas Thiazolidinediones DPP-4 inhibitors GLP-1 agonists Others
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)
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
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)
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
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
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
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
standard Treatment for DKA
IV fluids
IV insulin
Potassium replacement
standard Treatment for DM type I
Insulin
standard Treatment for DM type II
Low carb diet, wt loss, oral hypoglycemic agents, insulin
type 2 dm drug with lactic acidosis as rare but worrisome side effect
Metformin
type 2 dm drug with hypoglycemia as most common SE
Sulfonylureas
type 2 dm drug with recommended first line treatment for most patients
Metformin
type 2 dm drug with Not safe in settings of hepatic dysfunction or CHF
TZD (Thiazolidinediones)
type 2 dm drug with should not be used in patients with elevated serum creatinine
Metformin
type 2 dm drug with Should not be used in pt with cirrhosis or inflammatory bowel disease
alpha-glucosidase inhibitors
type 2 dm drug with not associated with wt gain
Metformin
type 2 dm drug with metabolized by liver, excellent choice in pt with renal disase
TZDs
type 2 dm drug with MOA closing potassium channel on beta cells, epolarization, ca influx, insulin release
Sulfonylureas
type 2 dm drug with MOA inhibits alphaglucosidase at intestinal brush border
Alphaglucosidase inhibitors (acarbose/Miglitol)
type 2 dm drug with MOA agonist at PPARgamma receptors leading to improved target cell response to insulin
TZDs
type 2 dm drug with MOA decreasing hepatic gluconeogenesis
Metformin
type 2 dm drug with good for wt loss
GLP-agonists
type 2 dm drug with Avoid in hypoglycemia
sulfonylureas
type 2 dm drug with Best treatment for anyone with organ failure
Insulin
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
Leptin action
Inhibits Lateral hypothalamus
Stimulates ventromedial nuclei
Both reslut in satiety
What is seen in kwashiokor
skin lesions
edema
liver function
what is seen in marasmus
tissue and muscle wasting
loss of subcutaneous fat
what vitamins should vegetarians supplement in their diet
vitamin B12
Anti-GBM antibodies (IF)
Goodpasture syndrome
Kimmelstiel-Wilson lesions
Diabetic nephropathy
Spike and dome appearance
Membranous glomerulonephritis
Tram track appearance of subendothelial humps
Membranoproliferative glomerulonephritis
subepithelial humps
Acute poststreptococcal glomerulonephritis
RLE of heme synthesis and its required cofactor
aminolevulinic acid synthase
Vit B6 is required cofactor
What makes aminolevulinic aci
glycine and succinyl CoA
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
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
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
What tumors can increase EPO?
Potentially Really High Hematocrit
Pheochromocytoma
Renal cell carcinoma
Hepatocellular carcinoma
Hemangioblastoma
*trisomy 21 at birth
Where does fetal erythropoesis occur?
yolk sac 3-8 wks
liver and spleen
bone marrow after 28 weeks
in which adult bones does erythropoiesis take place?
Vertebrae, ribs, pelvis
what substrate and cofactor for generating GABA
Glutamate and B6
what can iron deficiency manifest as
Plummer-Vinson syndrome:
Iron deficiency anemia
Esophageal webs
Atrophic glossitis
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)
Causes of macrocytic nonmegaloblastic anemia
Liver disease Alcoholism Reticulocytosis leading to increased MCV Drugs: -5-FU -Zidovudine -Hydroxyurea
Causes of normocytic nonhemolytic anemia
Anemia of chronic diseas e(can go to microcytic)
Aplastic anemia
CKD
women develops intense muscle cramps and darkening of her urine after exercise.
McArdle disease
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
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.
HUS-hemolytic uremic syndrome
associated with
classic triad, milder form of TTP
- hemolysis
- renal insufficiency
- thrombocytopenia
associated with E. coli 0157:H7 infectino
TTP pentad
FAT RN
or
Nasty Fever Torched His Kidneys
- hemolysis
- renal insufficiency
- thrombocytopenia
- neurological symptoms
- fever
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
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
DIC causes
STOP Making Thrombi
Sepsis Trauma Obstetric complications Acute Pancreatitis Malignancy Transfusion
fructose intolerance enzyme deficiency
aldolase b
essential fructosuria enzyme deficiency
fructokinase
classic galactosemia deficiency
galactose-1-phosphate uridyltransferase
Wiskott Aldrich
WAITER
- Wiskott
- Aldrich
- Immunodeficiency
- Thrombocytopenia and purpura
- Eczema
- Recurrent pyogenic infections
Hemosidinuria and thrombosis
PNH, paroxysmal nocturnal hemoglobinuria
Leukemia vs. lymphoma
Leukemia is in bone marrow or may spill into peripheral blood
Lymphoma is in lymph node
what is Marginal cell MALToma associated with
Sjogren syndrome
Hashimoto thyroiditis
H. pylori
most common type of non Hodgkin lymphoma in adults?
In children
adults: diffuse large B cell lymphoma
Children: lymphoblastic lymphoma
How does multiple myeloma present
anemia
renal insufficiency
back pain
hypercalcemia
Most common leukemia in children
ALL
most common leukemia in adults in US
CLL
Myelodysplastic syndromes have a tendence to progress to
AML
Myeloproliferative disorders may progress to
AML
Numerous basophils, splenomegaly, negative for leukocyte alkaline phosphatase (LAP)
CML