theme 1 (pt. 2 - pathology)

hypertrophy

• increase in size of cells → increase size organ

atrophy

• reduce in cell size or cell number

• may result in drecrease in size of organ

hyperplasia

• increase in number of cells → increase size of organ

• only in organs with stem cells that can diff and mature 

metaplasia 

• substitution of one differentiated cell/tissue type for another type of cell 

reversible changes

• reduced oxidative phosphorylation

• ATP depletion

• cellular swelling → swelling of endoplasmic reticulum and mitochondria

irrevesible changes

• mitochondrial irreversibility

• irrev membrane defects

• lysosomal digestion

apoptosis intrinsic pathway = 3 steps

1. cell injury → growth factor withdrawal, DNA damage, protein misfolding

2. Bcl-2 damily sensors → mitochondria → pro-apop proteins → initatior caspases 

3. executioner caspases

apoptosis extrinsic pathway = 3 steps

1. receptor-ligans interactions → Fas, TNF rec

2. adapter proteins → iniator caspases

3. executioner caspases

executioner caspases

• endonuclease act → nuclear fragmentation

• breakdown cytoskeleton → blebs

• apoptotic bodies → with ligands for phagocytic cell rec

necrosis vs apoptosis

• cell size

• nucleus

• plasma membrane

• cellular content

• adjacent inflammation

• physio/patho

• enlarged (swell) - reduced (shrinkage)

• karyolysis - fragmentation

• disrupted - intact

• enzymatic digestion - may be intact

• frequent/triggered - no

• patho - physio

coagulative necrosis

• hypoxic/low oxygen → mostly due to ischemia

• causes structures proteins to bend out of shape → don’t work

  • makes lysosomal proteins no longer effective at removing affected proteins

• cell dies → retain some structure (not completely destroyed)

liquefactive necrosis

• hydrolytic enzymes completely digest dead cells → creamy substance = dead immune cells

• pus = neutrophils

• capsule = fibroblasts

• mostly in brain, pancreas too

gangrenous necrosis

• hypoxia (form of coag necrosis)

• usually affects lower limbs and GI tract

• tissue dried up (mummy) → dry gangrene

• infected → liquefactive necrosis → wet gangrene 

caseous necrosis

• mix of coag and lique

• result of fungal or myobacterial infection

• mycobac → TB → cells disintegrate, but not fully digested 

• tissue looks like cottage cheese consistency

fat necrosis

• trauma to fatty organs that have a lot of adipocytes 

• adipocyte mem ruptures → spill fatty acids in extracellular space

• fatty acids + Ca → dystrophic calcification in tissue (chalk) 

• pancreatitis 

fibrinoid necrosis

• malignant hypertension and vasculitis 

• constant high pressure → damages walls of small arteries

• fibrin starts infiltrating and damaging walls

• vasculitis → infla reaction → destruction

inflammation starts with vascular changes 4/2 steps

• increased blood flow → caused by NO, histamin

  • expanding of arterioles and cap bed → rubor + calor 

• increased vasc permeabilitty → protein leakage → edema 

  • caused by histamin, bradykinin, leukotriens 

• stasis → low flow 

• neutrophil emigration 

neutrophil

• first responder

• segmented nucleus → 3-5 pieces

monocyte → macrophage

• cleans dead cells/pathogens

• nucleus looks like kidney 

• often vacuoles

• produceses histamin/TNF-a/IL-1 → calls more cells

lymphocyte

• small, big round nucleus

• little cytoplasm

• last to arrive/react

why do neutrophils arrive first

• endothelium has ready made binding points for neutrophils

• P/E-selectin → release upon first sign of danger

• binding points for monocytes have to be created from scratch (12-48 hours)

what causes vasodilation

NO (and prostaglandins = NSAID)

what causes increased vascular permeability

vasoactive amines

what causes fever = 3

IL1, IL6, TNFa

what causes tissue damage 2/3

• neutrophil and macrophage lysosomal enzymes

• NO

effect of microbial TLR ligands IFN-y on monocyte

• stim → classically act macrophage = M1

• inhib → alt act mp = M2

effect of IL13 and IL4 on monocyte

• stim → M2 (alt)

• inhib → M1 (class) 

M1 leads to 

• ROS, NO, lysosomal enzymes → killing bac and fungi

• IL1, IL12, IL23, chemokines → pathologic inflammation

M2 leads to

• IL10, TGFb → anti-inflam effect (inhib infla effect of M1)

• arginase, proline, polyaminases, TGFb → wound repair, fibrosis 

acute inflammation

• neutrophils dominate

• rapid onset → shot duration (min-days)

• pus, oedema, congested vessels

• limited tissue injury 

chronic inflammation

• lymphocytes (and macrophages) dominate 

• long duration (week-years)

• often follows persistent infection

  • ongoing cytokine release, tissue destruction + repair

  • fibrosis, angiogenesis → attempts at healing

what if even inflammation can’t repair the problem then what?

• granuloma → organized collection of activated macrophages, often epitheloid cells + gaint cells

  • surrounded by lymphocytes

granuloma with(out) necrosis

• with necrosis → caseating

  • eg → TBC, other mo’s

• without necrosis → non-caseating

  • AI or mo’s