more on Tc

what simple test tests for Tc function?anergy panel skin test. examples include: PPD, Candida, Trichophyton, tetanus toxoid, saline control). it is an example of delayed HS (HS 4). for a test to be +ve, Tc function must be preserved. remember, that HS1-3 is mediated by B cells.


what interferes with a anergy panel?

• corticosteroids (topical/ high dose systemic)
• anticoagulants (you get a skin induration because fibrin deposition, which is absent in settings of anticoagulants use)
• technique (i.e doctor's mistake at not injecting the antigen intradermally)
• infection (HIV = no functioning Tc, EBV, TB, leprosy)
• autoimmune disease (R.A, SLE, sarcoid)
• malnutrition
• pregnancy
• malignancy (eg: Hodgkin's lymphoma)

what assays test for Tc?
flow cytometry for CD3, 4, 8, 45 and Tc receptor

oh, dear

apparently i've spelt minuscule wrong all along.

i really didn't know that until spell check put underlined it with that wavy red line.

cell markers

CD3: all Tc
CD4: Th c
         60-70% of Tc in blood and lymphoid tissues.
         receptor for HIV
CD8: marker for Tk c (cytotoxic Tc)
CD19, 20: Bc
CD16, 56: NK c

Tc markers have functional significance, whereas Bc markers have a maturational significance.

immuno revisited

let's go over some factoids regarding ILs (interleukins)...those itty-bitty things that make immuno seem impossible at times!

• type of IL that boosts T helper cell?
  IL-2
• btw, normal Tc to Bc ratio?
  3:1
• causes an increase in temperature?
  TNF-alfa and IL-1
• revs up IgA?
  IL-5
• IL involved in helminthic infections?
  IL-5 (it revs up both IgA [intestinal mucosa] and eosinophils = activated at helminthic infections)
• responsible for endotoxin septic shock and causes cachexia in malignancies?
  TNF-alfa
• bonus question: where does TNF-alfa come from?
  it is secreted by macrophages
• another point if you can tell me the mechanism for how it causes cachexia?
  it inhibits lipoprotein lipase in adipose tissues
• interesting connection you can make:
  TNF-alfa activates IL-2 and Bc
• major, major must know fact: at HS1 (hypersensitivity type 1), which IL is the main culprit? think before looking at answer!
  did you guess IL5? (boo). TNF-alfa? (booooo).
  the answer is: IL-4, which then revs up IgE --> anaphylactic shock!
• IL responsible for activating stem cells?
  IL-3 (i remember this with a silly mnemonic: tree of life --> stem c are new life --> IL3)
• acute phase of inflamation...2 main ILs?
  IL-1 (remember...fever!) and IL-6 (acts as GM-CSF)
• mature monocytes secrete what CKs?
  first, you must answer...what are mature monocytes? MACROPHAGES! (back to the histo books for you if you didn't know that), so what did i say earlier? mphags secrete TNF-alfa and IL-1
• where are mphags fixed in tissues and what mediator activates them?
  recall that in liver cells, mphags = Kuppfer cells and C5a is needed to get them a moving again.

it is said the human brain at one time can retain 7 active items in its memory. i've given you 14 for now :) time to give these factoids a good home in your cerebellum :)

icannotbreathe!

ARDS (acute respiratory distress syndrome) carries a 50% death rate. stuff you should know or die:

• main causes?
  ischemic shock, DIC, endotoxin release (septic shock), illicit drug use, acute pancreatitis, breathing in really hot air
• main cell responsible?
  NEUTROPHILS!
• so, one of the features of ARDS is pulmonary edema. how do we differentiate this from say...cardiogenic pulmonary edema?
  pulmonary capillary wedge pressure (LV) *please review the physio part of this if you feel like you've never heard this before*
  it is low in ARDS and high in cardiogenic pulm. ed.
  

adrenals gone bad

let's do a review of some endocrine pathologies, shall we?

starting with my most favourite: Cushing's syndrome.

what is it? an increase of cortisol due to various reasons, which can be divided into:

• exogenous: steroid intake (iatrogenic)

• endogenous:
  
  1. cushing's disease (70%). a pituitary adenoma secreting excess ACTH, which in turn increases secretion of cortisol from the adrenals. serum shows an increase in both ACTH and cortisol.
  2. ectopic ACTH, made by non pituitary tissues (small cell lung cancer, bronchial carcinoids). serum will show an increase in both ACTH and cortisol.
  3. adrenal adenoma, carcinoma, nodular hyperplasia. ACTH levels would be LOW.

how do we test for it and differentiate between the three?

Dexamethasone suppression test  

• in healthy individuals, cortisol levels drop after a low dose of dexamethasone (the increase in cortisol, inhibits secretion of ACTH, which means there's no stimulation for the adrenals to produce cortisol)
  
• in an ACTH producing pituitary tumor (1), the cortisol levels increase after a low dose, but decrease after a high dose.
  
  now, you have a tissues producing excess ACTH, with almost no negative feedback from cortisol. that's why a low dose of exogenous steroid (dexamethasone) fails to inhibits further ACTH secretion and therefore the levels of cortisol still appear high. when a bigger dose of dexamethasone is administered, the negative feedback system is triggered to decrease the cortisol level.
  
  so, low dose dexamethasone, cortisol levels high. high dose dexamethasone, cortisol levels drop.
  
• ectopic ACTH producing tissues (2) and adrenal adenomas (3) differ in the sense that they are not influenced by the hypothalamus-pituitary-adrenal axis, and therefor not subjected to the negative feedback system.
  
  so, both a low and high dose of dexamethasone will result in high cortisol levels.

now onto HYPERALDOSTERONISM. two types exist:

1. primary (Conn's syndrome): aldosterone secreting tumor (uni/bilatera) that results in hypertension, hypoK+, metabolic alkalosis, low plasma renin.
   
   
2. secondary: kidney perceives low intravascular volume (due to renal artery stenosis, CHF, CRF, cirrhosis, nephrotic syndrome) and this results in an overactive renin-angiotensin-aldosteron activation. key point here is: PLASMA RENIN WOULD BE HIGH.

treatment? spironolactone, an aldosterone antagonist (its MOA as a K+ sparring diuretic).

next up: ADDISON'S.

• chronic adrenal insufficiency due to adrenal hypoplasia (primary = problem at adrenal) . results in total absence of hormones from all three layers of the adrenal cortex (primary deficiency of cortisol and aldosterone = hypotension).
  
  skin pigmentation occurs due to increase MSH, a by product of ACTH, which is increased because the pituitary tries stimulating the non responding adrenals.
  
  so increased ACTH, low adrenal hormones (salt, sugar, sex), high MSH = hyperpigmentation (bronze).
  
• secondary adrenal insufficiency = problem at pituitary. so ACTH would be LOW, no skin hyperpigmentation and no hyperkalemia.

that's all for today folks. stay tuned =)