Programmed cell death. Apoptotic genes – “programmed to die” (theory). Normal functions: (1)
embryo – small bowel got lumens from apoptosis. (2) King of the body – Y c’some (for men); MIF
very imp b/c all mullarian structures (uterus, cervix, upper 1/3 of vagina) are gone, therefore, no
mullarian structures. MIF is a signal working with apoptosis, via caspasases. They destroy
everything, then wrap everything in apoptotic bodies to be destroyed, and lipofuscin is left over.
(3)For woman – X c’some; only have one functioning one b/c the other is a barr body. Absence of y
c’some caused germinal ridge to go the ovarian route, therefore apoptosis knocked off the wolfian
structures (epidydymis, seminal vesicles, and vas deferens). (4) Thymus in anterior mediastinum –
large in kids; if absent, it is DiGeorge syndrome (absent thymic shadow), and would also have
tetany; cause of thymus to involute is apoptosis. (5) Apoptosis is the major cancer killing
mechanism. (6) Process of atrophy and reduced cell or tissue mass is due to apoptosis. Ex. Hepatitis
– councilman body (looks like eosinophilic cell without apoptosis) of apoptosis (individual cell death
with inflammation around it). Just needs a signal (hormone or chemical) which activate the
caspases, and no inflammation is around it. Apoptosis of neurons – loss brain mass and brain
atrophy, and leads to ischemia. Red cytoplasm, and pynotic nucleas. Atherosclerotic plaque.
Therefore, apoptosis is involved in embryo, pathology, and knocking off cancer cells.
Types of necrosis – manifestations of tissue damage.
A. Coagulation Necrosis: Results often from a sudden cutoff of blood supply to an organ i.e.
Ischemia (definition of ischemia = decrease in arterial blood flow). In ischemia, there is no oxygen
therefore lactic acid builds up, and leads to coagulation necrosis. Gross manifestation of
coagulation necrosis is infarction. Under microscope, looks like cardiac muscle but there are no
striations, no nuclei, bright red, no inflammatory infiltrate, all due to lactic acid that has denatured
and destroyed all the enzymes (cannot be broken down – neutrophils need to come in from the
outside to breakdown). Therefore, vague outlines = coagulation necrosis (see color change in
1. Pale vs hemorrhagic infarctions: look at consistency of tissue.
(a) Good consistency = grossly look pale: infarct: heart, kidney, spleen, liver (rarest of the organ
to infarct b/c dual blood supply); ie coagulation necrosis. Example of a pale infarction of the
spleen, most likely due to emboli from left side of heart; causes of emboli: vegetations (rarely
embolize in acute rheumatic endocarditis); infective endocarditis; mitral stenosis (heart is
repeatedly attacked by group A beta hemolytic streptococcus); and clots/thrombi. The worst
arrhythmia associated with embolization in the systemic circulation is atrial fib b/c there is stasis
in the atria, clot formation, then it vibrates (lil pieces of clot embolize).
Gangrenous Necrosis: dry and wet gangrene: Picture of a dry gangrene – not wet gangrene b/c
there’s no pus. Occurs in diabetic’s with atherosclerosis of popliteal artery and possible
thrombosis; (dry gangrene related to coagulation necrosis related with ischemia (definition of
ischemia = decrease in arterial blood flow), which is due to atherosclerosis of the popliteal
artery. Pathogenesis of MI: coronary thrombosis overlying the atheromatous plaque, leading to
ischemia, and lumen is blocked due to thrombosis. MCC nontraumatic amputation = diabetes
b/c enhanced atherosclerosis (popliteal artery = dangerous artery). Coronary is also dangerous b/c small lumen. In wet gangrene, it’s complicated by infective heterolysis and consequent
(b) Loose consistency of tissue= hemorrhagic infarct: bowel, testes (torsion of the testes),
especially the lungs b/c is has a loose consistency and when the blood vessels rupture, the RBC’s
will trickle out, leading to a hemorrhagic appearance.
Example: hemorrhagic infarction of small bowel due to indirect hernia. 2 MCC of bowel
infarction is getting a piece of small bowel trapped in indirect hernial sac. MCC of bowel
infarction is adhesions from previous surgery.
Example: In the Lung – hemorrhagic infarction, wedge shaped, went to pleural surface,
therefore have effusion and exudates; neutrophils in it; have pleuritic chest pain (knife-like pain
on inspiration). Pulmonary embolus leads to hemorrhagic infarction.
B. Liquefactive Necrosis:
Exception to rule of Coagulation necrosis seen with infarctions: brain.
MC site of infarction from carotid artery – why we listen for a bruit (hearing for a noise that is
going thru a vessel that has a narrow lumen – place with thrombus develops over
atherosclerotic plaque and leads to stroke); leads to transient ischemic attacks is little
atherosclerotic plaques going to little vessels of the brain, producing motor and sensory
abnormalities, that go away in 24 hrs. Brain with ‘meshwork’ – in brain, astrocytes is analogous
to the fibroblasts b/c of protoplasmic processes. Therefore, acting like fibroblast (can’t make
collagen), but its protoplasmic processes gives some structure to the brain. Therefore,
infarction of the brain basically liquefies it (has no struct), and you see a cyst space –
liquefactive necrosis. Therefore, exception to the rule of infarctions not being coagulative
necrosis is the brain and it undergoes liquefactive necrosis (no struc, therefore leaves a hole).
Cerebral abscess and old atherosclerotic stroke -both are liquefactive necrosis.
Liquefactive – liquefies; think neutrophil, b/c their job is to phagocytosis with their enzymes (to
‘liquefy’); liquefactive necrosis relates to an infection with neutrophils involved (usually acute
infection – producing an abscess or an inflammatory condition, which liquefies tissue).
Therefore, liquefactive necrosis usually applies to acute inflammation, related to neutrophils
damaging the tissue. Exception to the rule: liquefactive necrosis related to infarct (not an
inflammatory condition, it just liquefies) (slide shows liquefactive necrosis due to infection in the
brain). So, if you infarct the brain, or have an infection, or have an abscess it is the same process
– liquefactive necrosis.
Example: Abscess – gram “+” cocci in clusters. Why are they in clusters? Coagulase, which leads
to abscesses with staph aur. Coagulase converts fibrinogen into fibrin, so it localizes the
infection, fibrin strands get out, resulting in an abscess. Strep: releases hyaluronidase, which
breaks down GAG’s in tissue, and infection spreads through the tissue (cellulitis). From point of
view of necrosis, neutrophils are involved, therefore it is liquefactive necrosis.
Example: ABSCESS: Lung – yellowish areas, high fever and productive cough; gram stain showed
gram “+” diplococcus, which is strep pneumoniae. (MCC of bronchopneumonia.). Not
hemorrhagic b/c its pale, and wedged shaped necrosis at the periphery, which leads to pleuritic
chest pain. Example: pt with fever, night sweats, wt loss – M tb, which has granulomatous (caseous)
necrosis. Pathogenesis of granuloma (involves IL-12 and subset of helper T cells and “+” PPD).
C. Caseous (cheesy consistency) Necrosis: – either have mycobacterial infection (any infections,
including atypicals, or systemic fungal infection); these are the ONLY things that will produce
caseation in a granuloma. It is the lipid in the cell wall of the organism’s leads to cheesy appearance.
Sarcoidosis – get granulomas, but they are not caseous b/c they are not mybacterium or systemic
fungi (hence ‘noncaseating’ granulomas)
Crohn’s dz – get granulomas, but not caseous b/c not related to mycobacterium or systemic fungi.
1. Enzymatic Fat Necrosis: unique to pancreas
Example: pt with epigastric distress with pain radiating to the back – pancreatitis (cannot be
Peptic Ulcer Dz b/c pancreas is retroperitoneal), therefore just have epigastric pain radiating to
the back. A type of enzymati