B7PBL

• complex glycopeptides: TSH, LH, FSH, hCG (common alpha, unique beta chains)
• proteins: ACTH, GH, Prolactin
• intermediate sized peptides: insulin, glucagon
• small peptides: TRH
• dipeptides: T4, T3
• derivatives of single amino acids: catecholamines, serotonin (tyrosine)

• intact steroid nucleus: testosterone, cortisol
• cleaved B ring: vitamin D and metabolites

• 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
• suppress appetite
• increase energy expenditure
• -Regulate reproduction (higher = earlier puberty)
• -Modulate immune system (def = dec in CD4)

• NeuroD1: ACTH
• GATA2, SF-1: LH/FSH
• Pit-1: GH, PRL, TSH (and GATA2)

• Injury: head trauma, surgery, radiation
• Tumor
• Infiltrative Disorders: Histiocytosis X, sarcoid

• -Pituitary Adenoma
• -Non-pit causes
• craniopharyngioma
• cysts
• arteriovenous malformations
• lymphocytic hypophysitis

• Inhibitory control! = dopamine from hypothalamus
• Stimulatory = TRH, prolactin stimulator hormone
• Neuro-endocrine reflex arc = nipple stimulation inhibits dopa release from hypothalamus

• GHRH (stress, sleep, exercise) = stimulate
• somatostatin, IGF-1 = inhibit
• both regulated by CNS
• GH secretion is pulsatile (6-12/day)

• IGF-1:
• liner growth in kids
• increase protein synthesis
• mobilize fats
• decreases insulin resistance!!
• GH:
• increase hepatic glucose production and decrease glucose uptake into cells

• bromocriptine
• somatostatin
• pegvisomany (somavert): GH-R antagonist

• GLUT 2 = transporter
• hexokinase
• more ATP=K channel closes...Insulin release!
• insulin receptors on beta cells lead to upregulation of hexokinase

antibodies to GAD

extrusion of GAD is an apoptotic signal for beta cells, along with too much glucose, fats

• insulin deficiency
• serum C-peptide = best test of beta cell reserve
• best tests for islet cell autoimmunity = anti-GAD65, anti-tyrosine phosphatase (15-20%)

• Total Daily Dose = 0.5 units/kg/day
• 50% of TDD = Basal insulin (glargine)
• 50% of TDD = mealtime boluses (aspart)

• formed by Amadori reaction complexing glucose with amines, indicators of long-term extent of hyperglycemia
• -HbA1c is a good example!

• mesangial expansion-->kimmelsteil-wilson nodular glomerulosclerosis
• -correlates with GBM thickening and microalbuminuria
• 
• treat with ACEi or ARB

• -stiff hand syndrome "prayer sign"
• -trigger finger

• fasting ≥126
• random ≥200 (with classic symptoms of DM)
• OR
• 2 hr postprandial ≥ 200 (OGTT)
• OR
• A1c ≥6.5%

• serine phosphorylation of insulin receptor
• intracellular free fatty acids (nefas)

apoptotic signal (it's made with insulin)

no hypoglycemia as monotherapy

• insulin secretagogues
• -50% of dose gives you 80% response

weight gain, hypoglycemia, inc risk CVD

safe choice in the elderly; more postprandial hyperglycemia and less fasting

• indolent loss of insulin secretory capability.
• -anti-GADs are present
• -progressive dec in c peptide
• -NO ketoacidosis
• Typical: middle aged, non-obese, no real Fam Hx

• A1c < 7%
• fasting ~ 100
• 2hr postpran <150

• produced early in pregnancy to stimulate corpus luteum to continue producing progesterone for the first 8 weeks
• suppresses maternal immune function (rejection)

• It's a placental lactogen/growth hormone
• -Effects are opposite those of insulin
• -mom can use fat for energy, glucose and protein go to fetus

• 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

• Gland enlarges 2-3x (lactotrophs)
• LH, FSH, GH are low
• ACTH goes up (increase CRH)

Sheehan's, lymphocytic hypophysitis

total t3,4 increased d/t increase in TBG (synthesis, inhibition of breakdown by estrogen)

grave's is most common - treat with PTU

• increase fetal loss (30-40%)
• insulin resistance--metformin can help

• WT1 --> urogenital ridge
• SRY--> SOX9 is like it...DAX-1 blocks it to make girls
• WNT-4: Meyer-Ritanski syndrome
• DAX-1(anti-testis): blocked by SRY
• double DAX = girl...careful when you look at karyotypes

• Classic: 21-Hydroxylase deficiency
• -hyponatremia
• -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

• -many are mediated by IGF-1
• -pulsatile release. stages III, IV of sleep

• 2nd year > 10 cm/yr
• 8cm 3rd year
• 7cm 4th year
• 4-6 cm/year from 4 to puberty

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)

IGF-1 deficiency d/t GH insensitivity

• haploinsufficiency of short stature homeobox-containing (SHOX) gene
• -found distal tip of X and Y
• -doesn't get inactivated...need both copies

primary hyperparathyroidism

it's that cancer

• lithium
• thiazide diuretics

low Mg impairs PT function...PTH synthesis and release and PTH resistance

-Common: cis-platinum chemo and alcoholism

check that urinary Ca. could be the familial hypocalciuric hypercalcemia

• RET gene mutation = test everyone
• a.MTC
• Pheo
• Parathyroid
• cutaneous lichen amyloidosis
• Hirschsprung disease

• b.MTC
• Pheo
• mucosal and GI (even mouth) neuromas...marfinoid habitus

• Parathyroid adenoma
• Pancreatic (Z-E)
• Pituitary (prolactinoma)

MEN1 mutation = tumor suppressor

• Papillary.
• females, 40s, juxtanodal invasion, 6% mortality

• hypoglycemia:
• symptoms c/w neuroglycopenia AND
• measured glucose < 55 (not fingerstick) AND
• rapid resolution (5min) of sx w/ ingestion or IV admin of glucose

autoimmune thyroiditis and autoimmune adrenalitis

-hypothyroid and ...

• worst HA of life, sudden onset, holocranial 10/10 pain
• -hemorrhagic or edematous infarction of pituitary tumor
• -Tx: steroids, surgical decompression

• C: hypocalcemia: facial muscle spasm upon tapping.
• T: hypocalcemia: occlusion of brachial artery with BP cuff-->carpal spasm

• -Cause of post-op hypocalcemia
• low PO4
• high alk phos

• ARF
• ATN: some say synonymous b/c it's the most common intrinsic cause
• ARI
• ARIRF: acute reversible intrinsic renal failure

you need to have a hemodynamic change and(/or???) some nephrotoxin...

toxins: sepsis, NSAIDs, epinephrine

eosinophils are seen on biopsy

• Prerenal azotemia: >40
• Intrinsic: <20

= excreted solute/filtered solute

= (U_Na x V) / (GFR x P_Na) = (U_Na / P_Na)/(U_Cr/P_Cr)

• -Prerenal: <1%
• -Renal: >2%

• Azotemia >3 mo
• uremia sx
• small kidneys
• edema, HTN, polyuria, nocturia
• proteinuria, electrolyte disorders
• broad, waxy casts in sediment

• epithelial
• mixed cell/ granular
• coarse granular
• fine granular
• waxy

• AIDS
• IV drug use (heroin)

dysmorphic cells and RBC casts

• 30
• -Citrate complexes Ca and prevents CaOx crystallization

• 25-30
• -Promotes CaOx crystallization

• 2nd in US (10%)
• -Age = risk factor
• Beneficial?
• fat
• selenium
• vitamin D
• retinoids
• lycopenes

transrectal us guided biopsy (TRUSP)

• simple cyst
• -don't know the patho...cysts begin as dilatation of intact tubules in contact with nephrons...fill by filtration

-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
• Dx: <30 = 2 cysts, 30-59 2 in each, <60 4 in each
• Sx: HTN, hematuria, UTI, stone, failure, cysts outside kidney
• CV: mitral prolapse in 25%
• Intracranial aneurysms!!! (4-10%) screen CT or MRA (preferred). MCA most common. ACEi.
• Thoracic and AAA

• -AD
• -Retinal angiomas, cerebellar and spinal hemangiomas and pheos
• -70-80% have renal cysts
• -40-60% RCC, bilateral, multicentric

• -AD on 9 and 16 (close to ADPKD)
• -angiomyopiomas of kidney are common
• -renal failure = most common serious manifestation above 30

• small protein
• elemental zinc cofactor
• diminished at time of UTI

• pyelo in normal ut
• colonizes vagina/foreskin
• ascends tract
• cell binding

• cystitis
• binds to Tamm-Horsfall
• binds latex caths
• inhibited by mannose

• stones
• catheter
• DM
• male
• sepsis
• old
• obstruction

upper tract eval, prolonged therapy, parenteral antibiotics?

• US = first imaging
• CT most specific
• UA is helpful
• CandS critical

• complication of UTI
• -triad: flank mass, nonfunction, ipsilateral stones
• -foam cells in urine
• -abnormal LFTs?
• -relapsing UTI

bladder, renal, lung, and adrenal involvement

• M-G bodies: basophilic inclusions
• large mononuclear phagocytes

• 1: <90 and persistent albuminuria
• 2: 60-89 '' ''
• 3: 30-59 ml/min per 1.73m2 (7.7%)
• 4: 15-29 '' '' '' (0.21%)
• 5: <15 or ESRD (2.4%)

• <130/80
• ACEi or ARB: reduce kidney damage in the long run, even if creatinine rises initially

• 2 reading <140/90 and 2 normals
• -ambulatory pressure monitoring for eval

• pain (180-200)
• drug-induced : NSAID, oral contraceptives

lisinopril and HCTZ

metoprolol and HCTZ are both diabetogenic...the ACEi is not!

bruit: systolic with a diastolic component

intra-arterial digital subtraction angiography...b/c you can fix it at the same time.

fasting glucose, lipid profile, and serum calcium

other suggestions (JNC7): EKG, UA, Hct, K, Cr

cardiovascular disease complications (half of mortality)

Nope. beta-2 microglobulins and leptin do it too.

• hyperkalemia
• fluid overload, pulmonary edema
• severe acidemia
• pericarditis
• encephalopathy

• small-->diffusion
• big-->convection

middle molecules are removed more efficiently

• HypoTn
• bleeding
• cramps
• air embolism
• Dialysis Dysequilibrium: high BUN-->fluid in brain

• 1.Aquaporins! 5-10 angstroms. 50% of water removal.
• 2. Parasternal
• 3. negative pressure
• 4. infection! multiple=non-functioning peritoneum

• Adults: Kids:
• 1.Diabetes 1. Nil/FGS
• 2.Membranous 2. MPGN
• 3.Nil/FGS 3. IgA/H-SP
• 4. Amyloidosis 4. Membranous

• segmental scars
• foot effacement
• no deposits
• negative for IF or segmental IgM, C3
• tends to begin at CMJ
• -progresses to ESRD frequently!
• -recurs in transplants!
• *associated with AIDS, IVDuse

• Immune complex-mediated - supEPIthelial - granular deposition of IgG and C3
• Stages:
• 1. looks normal
• 2. fuzzy membranes
• 3. domes
• 4. very thick
• -Secondary causes: 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.

• it's the most common form of GN. most frequent cause of ESRD (30%).
• mesangial hypercellularity
• mesangial immune deposits
• mesangial IF with IgA and C3

• acute diffuse proliferation-->exudative, lots of PMNs
• -dec GFR, dark pee
• -IF looks like MPGN

• not a dx
• DDx: idiopathic, anti-GBM, Wegener, PAN, cryoglobulinemia, SLE, IgA Nephropathy, PSGN, HSP, MPGN, endocarditis, HepB, serum sickness, paraprotein-induced, membranous-associated
• -ANCA: c=Weg, p=MPA, PAN

• I: normal
• II: mesangial a. pos IF, EM b.hypercellular
• III: Focal
• IV: Diffuse (subendothelial deposits)
• V: Membranous (subepithelial)
• VI: Advanced Sclerosing GN

watch out for small vessel thrombosis (anti-phospholipid antibodies)

• nephrotic
• mesangial expansion (NEGs)
• mesangial nodules (Kimmelstien-Wilson)
• EM shows GBM thickening
• IF negative