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B7PBL Lecture Notecards
What are the amino acid derived hormones?
: TSH, LH, FSH, hCG (common alpha, unique beta chains)
: ACTH, GH, Prolactin
intermediate sized peptides
: insulin, glucagon
: T4, T3
derivatives of single amino acids
: catecholamines, serotonin (tyrosine)
What are the steroid hormones (derivatives of cholesterol)?
ntact steroid nucleus
: testosterone, cortisol
cleaved B ring
: vitamin D and metabolites
What are the transporters of water-insoluble hormones?
Thyroid binding globulin
sex hormone binding globulin
corticosteroid binding globulin
-changes in binders cause change in total, not free
only the free fraction is biologically active!
free fraction regulated, not total!!!
-Regulates fat and thus weight
increase energy expenditure
-Regulate reproduction (higher = earlier puberty)
-Modulate immune system (def = dec in CD4)
What stimulates the growth of different pituitary cells?
: GH, PRL, TSH (and GATA2)
How can you hurt the hypothalamus?
: head trauma, surgery, radiation
: Histiocytosis X, sarcoid
Control of prolactin production?
Inhibitory control! = dopamine from hypothalamus
Stimulatory = TRH, prolactin stimulator hormone
Neuro-endocrine reflex arc = nipple stimulation inhibits dopa release from hypothalamus
Growth Hormone regulation?
GHRH (stress, sleep, exercise) = stimulate
somatostatin, IGF-1 = inhibit
both regulated by CNS
GH secretion is pulsatile (6-12/day)
Action of GH and IGF-1?
liner growth in kids
increase protein synthesis
decreases insulin resistance!!
increase hepatic glucose production and decrease glucose uptake into cells
Treatment of acromegaly?
: GH-R antagonist
What happens when the beta cell senses high glucose?
GLUT 2 = transporter
more ATP=K channel closes...Insulin release!
insulin receptors on beta cells lead to upregulation of hexokinase
What's the best marker for type I DM?
antibodies to GAD
extrusion of GAD is an apoptotic signal for beta cells, along with too much glucose, fats
What are some useful markers for Dx of Type I DM?
serum C-peptide = best test of beta cell reserve
best tests for islet cell autoimmunity = anti-GAD65, anti-tyrosine phosphatase (15-20%)
How does insulin therapy work?
Total Daily Dose = 0.5 units/kg/day
50% of TDD = Basal insulin (glargine)
50% of TDD = mealtime boluses (aspart)
What are blood advanced glycosylation endproducts (AGEs)?
formed by Amadori reaction complexing glucose with amines, indicators of long-term extent of hyperglycemia
-HbA1c is a good example!
Diabetic Nephropathy on LM?
mesangial expansion-->kimmelsteil-wilson nodular glomerulosclerosis
-correlates with GBM thickening and microalbuminuria
treat with ACEi or ARB
What's diabetic cheiroarthopathy?
What's Dupuytren's Contracture?
-stiff hand syndrome "prayer sign"
Dx of DM II
random ≥200 (with classic symptoms of DM)
2 hr postprandial ≥ 200 (OGTT)
What are some post-receptor defects in DM II?
serine phosphorylation of insulin receptor
intracellular free fatty acids (nefas)
Why does amylin matter in DM II?
apoptotic signal (it's made with insulin)
no hypoglycemia as monotherapy
sulfonylureas and meglitinides
-50% of dose gives you 80% response
weight gain, hypoglycemia, inc risk CVD
alpha-glucosidase inhibitors (acarbose)
safe choice in the elderly; more postprandial hyperglycemia and less fasting
What's Latent Autoimmune Diabetes of Adults (LADA)?
indolent loss of insulin secretory capability.
-anti-GADs are present
-progressive dec in c peptide
: middle aged, non-obese, no real Fam Hx
What are the ADA guidelines for glycemic control?
A1c < 7%
fasting ~ 100
2hr postpran <150
What does cHG do?
produced early in pregnancy to stimulate corpus luteum to continue producing progesterone for the first 8 weeks
suppresses maternal immune function (rejection)
What's human chorionic somammotropin (hCS)?
It's a placental lactogen/growth hormone
opposite those of insulin
-mom can use fat for energy, glucose and protein go to fetus
What's CRH's role in pregnancy?
Increases a lot throughout pregnancy.
may be important in the timing of parturition
-cortisol has POSITIVE feedback to wake up axis in fetus-->increased prostaglandins and delivery
Maternal Pituitary Changes?
Gland enlarges 2-3x (lactotrophs)
LH, FSH, GH are low
ACTH goes up (increase CRH)
Sheehan's, lymphocytic hypophysitis
maternal thyroid changes?
total t3,4 increased d/t increase in TBG (synthesis, inhibition of breakdown by estrogen)
grave's is most common - treat with PTU
PCOS and pregnancy
increase fetal loss (30-40%)
insulin resistance--metformin can help
What are some genes that play a role in early gonadal development?
WT1 --> urogenital ridge
SRY--> SOX9 is like it...DAX-1 blocks it to make girls
: Meyer-Ritanski syndrome
: blocked by SRY
double DAX = girl...careful when you look at karyotypes
What's Congenital Adrenal Hyperplasia?
: 21-Hydroxylase deficiency
-hypoglycemia (no cortisol)
-hyperkalemia (salt-wasting...don't lose K)
Order that 17-hydroxyprogesterone
Endogenous ligand of the Growth Hormone Secretogues-Receptor. GHS are man-made ligands capable of stimulating GH release.
found in stomach...and hypothalamus
stimulates food intake and obesity
Actions of Growth Hormone?
-many are mediated by IGF-1
-pulsatile release. stages III, IV of sleep
Growth Childhood-2 to Puberty
2nd year > 10 cm/yr
8cm 3rd year
7cm 4th year
4-6 cm/year from 4 to puberty
How do you calculate Mid-Parental Height?
males: ((mom's height + 13 cm) + (dad's height))/2
females: ((dad's -13cm) + (mom's))/2
13cm = 5 inches
SD=2.5 cm (6-10cm 95% of time)
What's Laron Syndrome?
IGF-1 deficiency d/t GH insensitivity
What's the etiology of short stature in Turner's?
haploinsufficiency of short stature homeobox-containing (SHOX) gene
-found distal tip of X and Y
-doesn't get inactivated...need both copies
What's the most common etiology of hypercalcemia?
what's the most common cuase of high calcium in hospital patients?
it's that cancer
What are two drugs you shouldn't take with primary hyperparathyroid?
What effect does Mg have on PTH function?
low Mg impairs PT function...PTH synthesis and release and PTH resistance
-Common: cis-platinum chemo and alcoholism
what do you need to check before taking out the parathyroids?
check that urinary Ca. could be the familial hypocalciuric hypercalcemia
What do you get with that MEN II a and b?
RET gene mutation = test everyone
cutaneous lichen amyloidosis
mucosal and GI (even mouth) neuromas...marfinoid habitus
What do you get with that MEN I?
MEN1 mutation = tumor suppressor
What's the most common thyroid cancer?
females, 40s, juxtanodal invasion, 6% mortality
What's Whipple's Triad?
symptoms c/w neuroglycopenia AND
measured glucose < 55 (not fingerstick) AND
rapid resolution (5min) of sx w/ ingestion or IV admin of glucose
What's Polyglandular Autoimmune Failure?
autoimmune thyroiditis and autoimmune adrenalitis
-hypothyroid and ...
What's pituitary apoplexy?
worst HA of life, sudden onset, holocranial 10/10 pain
-hemorrhagic or edematous infarction of pituitary tumor
: steroids, surgical decompression
What are Chvostek and Trousseau signs?
: hypocalcemia: facial muscle spasm upon tapping.
: hypocalcemia: occlusion of brachial artery with BP cuff-->carpal spasm
What is "Hungry Bone" syndrome?
-Cause of post-op hypocalcemia
high alk phos
What are the different names for Acute Renal Failure?
: some say synonymous b/c it's the most common intrinsic cause
: acute reversible intrinsic renal failure
How do you get ATN?
you need to have a hemodynamic change and(/or???) some nephrotoxin...
toxins: sepsis, NSAIDs, epinephrine
What do you get with AIN?
eosinophils are seen on biopsy
What's the BUN:creatinine for prerenal and intrinsic disease?
How do you calculate the fractional excretion of sodium (FEna)?
= excreted solute/filtered solute
x V) / (GFR x P
) = (U
What are some sx of CRF?
Azotemia >3 mo
edema, HTN, polyuria, nocturia
proteinuria, electrolyte disorders
broad, waxy casts in sediment
What's the age progression for casts?
mixed cell/ granular
What are two risk factors for focal glomerular sclerosis?
IV drug use (heroin)
What's a good indicator of glomerular disease?
dysmorphic cells and RBC casts
What % of stone formers are hypocitraturic?
-Citrate complexes Ca and prevents CaOx crystallization
What % of stone formers have hyperuricosuria?
-Promotes CaOx crystallization
Prostate Cancer death?
2nd in US (10%)
-Age = risk factor
How do you diagnose prostate ca?
transrectal us guided biopsy (TRUSP)
What's the most common mass in the adult kidney?
-don't know the patho...cysts begin as dilatation of intact tubules in contact with nephrons...fill by filtration
What are the PKD genes?
-polycystin-1 and -2, found in renal tubular epithelium, hepatic bile ducts, pancreatic ducts
-over expressed in cysts
-involved in cell-cell and protein-protein interxn
-loss in ADPKD causes dec intracell Ca and inc cAMP leading to cell prolif and cysts
4th commonest cause of ESRD
ADPKD1 most common. On Ch 16
ADPKD2 on 6
: <30 = 2 cysts, 30-59 2 in each, <60 4 in each
: HTN, hematuria, UTI, stone, failure, cysts outside kidney
: mitral prolapse in 25%
Intracranial aneurysms!!! (4-10%) screen CT or MRA (preferred). MCA most common. ACEi.
Thoracic and AAA
What's Von-Hippel Lindau disease?
-Retinal angiomas, cerebellar and spinal hemangiomas and pheos
-70-80% have renal cysts
-40-60% RCC, bilateral, multicentric
What's tuberous sclerosis?
-AD on 9 and 16 (close to ADPKD)
-angiomyopiomas of kidney are common
-renal failure = most common serious manifestation above 30
elemental zinc cofactor
diminished at time of UTI
pyelo in normal ut
What about that Type 1 (mannose sensitive) fimbriae?
binds to Tamm-Horsfall
binds latex caths
inhibited by mannose
What's a complicated UTI? so what?
upper tract eval, prolonged therapy, parenteral antibiotics?
How do you dx UTI?
US = first imaging
CT most specific
UA is helpful
What's xanthogranulomatous pyelonephritis?
complication of UTI
: flank mass, nonfunction, ipsilateral stones
-foam cells in urine
bladder, renal, lung, and adrenal involvement
: basophilic inclusions
large mononuclear phagocytes
What are the stages of kidney disease?
: <90 and persistent albuminuria
: 60-89 '' ''
: 30-59 ml/min per 1.73m2 (7.7%)
: 15-29 '' '' '' (0.21%)
: <15 or ESRD (2.4%)
What's the target blood pressure for CKD with HTN?
ACEi or ARB
: reduce kidney damage in the long run, even if creatinine rises initially
What's white coat HTN?
2 reading <140/90 and 2 normals
-ambulatory pressure monitoring for eval
What are some weird causes of HTN?
: NSAID, oral contraceptives
How do you treat HTN in a diabetic?
lisinopril and HCTZ
metoprolol and HCTZ are both diabetogenic...the ACEi is not!
What's the PE finding for renal artery stenosis?
bruit: systolic with a diastolic component
How do you diagnose renal artery stenosis?
intra-arterial digital subtraction angiography...b/c you can fix it at the same time.
What's the workup for essential HTN?
fasting glucose, lipid profile, and serum calcium
other suggestions (JNC7): EKG, UA, Hct, K, Cr
What do most people die from with ESRD?
cardiovascular disease complications (half of mortality)
Is urea responsible for all the ills of ESRD?
Nope. beta-2 microglobulins and leptin do it too.
What are the indications for urgent dialysis?
fluid overload, pulmonary edema
How are compounds removed in dialysis?
middle molecules are removed more efficiently
What are some complications of dialysis?
: high BUN-->fluid in brain
How does water move in peritoneal dialysis?
Where's the best cath site?
How does it work?
What's the big complication?
1.Aquaporins! 5-10 angstroms. 50% of water removal.
3. negative pressure
4. infection! multiple=non-functioning peritoneum
What's the DDx for nephrotic syndrome in adults?kids?
1.Diabetes 1. Nil/FGS
2.Membranous 2. MPGN
3.Nil/FGS 3. IgA/H-SP
4. Amyloidosis 4. Membranous
What's focal segmental glomerulosclerosis?
negative for IF or segmental IgM, C3
tends to begin at CMJ
-progresses to ESRD frequently!
-recurs in transplants!
*associated with AIDS, IVDuse
What's membranous GN?
Immune complex-mediated - supEPIthelial - granular deposition of IgG and C3
1. looks normal
2. fuzzy membranes
4. very thick
: NSAID, cancer, SLE, thyroiditis, infections
Type 1: more common, subENDOthelial, tram tracks. Classical complement pathway.
Type 2: dense deposit disease. Purely alternate complement pathway: C3 only!!! muddy pink GBM on silver stain. recurrence in transplants.
What's Berger's IgA nephropathy?
it's the most common form of GN. most frequent cause of ESRD (30%).
mesangial immune deposits
mesangial IF with IgA and C3
What's post-infectious GN?
acute diffuse proliferation-->exudative, lots of PMNs
-dec GFR, dark pee
-IF looks like MPGN
What's crescentic GN?
not a dx
: idiopathic, anti-GBM, Wegener, PAN, cryoglobulinemia, SLE, IgA Nephropathy, PSGN, HSP, MPGN, endocarditis, HepB, serum sickness, paraprotein-induced, membranous-associated
: c=Weg, p=MPA, PAN
What does lupus nephropathy look like?
: mesangial a. pos IF, EM b.hypercellular
: Diffuse (subendothelial deposits)
: Membranous (subepithelial)
: Advanced Sclerosing GN
watch out for small vessel thrombosis (anti-phospholipid antibodies)
What does diabetic nephropathy look like?
mesangial expansion (NEGs)
mesangial nodules (Kimmelstien-Wilson)
EM shows GBM thickening