Episode 51: Doctor Dan covers tissue repair and cellular response to injury in the kidney, lungs and nervous system. Also, get a quick review of inflammation in general to keep your memory fresh.

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I. Tissue Repair

Scar tissue (b/c its permanent tissue); scar tissue (fibrous tissue) does not contract; therefore, if you have more scar tissue to free wall of left ventricle will lead to decreased Ejection Fraction, which is Stroke Volume divided by the End Diastolic Volume.

EF = SV/EDV

A. Response of Kidneys to Injury:

Kidney will form scar tissue; medulla is most susceptible to ischemia (b/c least amount of blood supply). What part of nephron most susceptible to tissue hypoxia? 2 places:

1. Straight portion of prox tubule b/c most of oxidative metabolism is located there, with brush borders – this is where most of reabsorption of Na, and reclaiming of bicarb is there.

2. Medullary segment of thick ascending limb – where the Na/K-2Cl pump is – which is where loop diuretics block. The Na/K-2Cl pump generates free water. The two type of water in urine: obligated and free. If the water is obligated, then the water is obligated to go out with every Na, K, and Cl (concentrated urea). Basically 20 ml’s of obligated water for every Na, K, Cl (it’s obligated) via Na/K/2Cl pump. The ADH  hormone absorbs free water b/c the pump generates free water.

Let’s say you absorb one Na, how much free water is left behind in the urine? – 20 mls; then reabsorbed another K, that is another 20, so its up to 40; another 2 Cl’s are reabsorbed which is another 40; therefore, for absorbing one Na, one K, and 2 Cl’s, you have taken 80 mls of free water from the urine – this is free water that is generated; its is this pump that loop diuretics block, which is in the thick ascending limb of the medullary segment.

B. Response of Lungs to Injury:

Lung repair cell is type II pneumocyte (can also repair type I pneumocytes); it also synthesizes surfactant.

C. CNS

Repair cell is the astrocyte; the astrocyte proliferates (b/c it’s a stable cell, not a neuron), that can proliferate and produces protoplasmic processes – called gliosis (rxn to injury in the brain, which is due to astrocyte proliferation); this is analogous to fibroblasts laying collagen type 3 in the wound.

D. PNS

Wallarian degeneration is the mech of axonal regeneration. In PNS, have Schwann cells, while in the CNS, have oligodendrocytes (both make myelin). Tumor Schwann cell = schwannoma; if it involves CN VIII it is called acoustic neuroma. What genetic dz that is auto dominant has association? Neurofibromatosis.

II. Extra Side notes and Review of Inflammation:

A. ESR

Putting whole blood into cylinder and see when it settles. The higher the density, or weight, therefore settle pretty quick and therefore have a increased sedimentation rate. When stuck together and looks like coins = roulouex. When aggregated together = increased sed rate, which is increased IgG and fibrinogen (includes every acute and chronic inflammation there is.

  • What causes RBC’s to clump? – IgM, b/c the neg charge normally keeps RBC’s from stick to e/o.
  • IgM is a lot bigger; cold agglutinins are associated with IgM ab, leading to agglutinin. This is why in cold whether, you get Raynaud’s phenomenon (lips, nose, ears, toes, fingers turn blue). The IgM ab can cause cold agglutinins, leading to ischemia.
  • Another type of clumping of IgM are Cryoglobulins – Ig’s congeal in cold weather; IgM ab’s do the same thing. High assoc of hep C with cryoglobulins.
  • Multiple myleoma = increased esr b/c increased IgG; with waldenstroms, will see increased IgM (Waldenstrom’s Macroglobemia).

B. Acute appendicitis

Get CBC, and want to see absolute neutrophilic leukocytosis, meaning that you have an increase of neutrophils in the peripheral blood; also looking for toxic granulation, and a LEFT SHIFT. Assuming you start from myeloblast on the left, and eventually form a segmented neutrophil on the right; normally go left to right on maturation; therefore, with a left shift, its means that we go back to immature neutrophils; the definitions is greater than 10% band neutrophils is considered a LEFT SHIFT (all the neutrophils are bands); if you have just one metamyelocyte or one myelocyte, its is automatically considered a LEFT SHIFT.

In acute appendicitis, there is an absolute increase in neutrophils, with toxic granulation and a left shift.

C. O2 dependent myeloperoxidase system =

Most potent system for killing bugs. Myeloperoxidase is located in azurophilic granules, which are lysosomes. Want a lot of lysosome in an acute inflammatory rxn, b/c therefore there is more myeloperoxidase around for killing bugs – this is what toxic granulation. Therefore, toxic granulation ensures that there is enough myeloperoxidase to work that potent system to kill bugs (O2 dep myeloperoxidase system).

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