Lecture 1 Flashcards
Pathogenesis?
Developing a disease
Cellular response to injury depends
on the type, the duration and the severity of the injury
Consequences depend on
the type, the condition and the adaptability of the cell
The most important attack points in the cell:
plasma membrane, aerobic respiration, protein synthesis, genome
What follows the functional changes of a damaged cell?
Morphological changes
What kind of tissue or damage can a cell undergo?
Causes:
- Physical agents (mechanic, irradiation, electric, burn, thermic etc.)
- Chemical agents (toxins, drugs, bacterial toxins)
- Biological agents (microbes)
- Genetic defects
- Nutritional effects (qualitative/ quantitative malnutrition)
- Oxigen and nutrition deficiency (ischemia, hypoxia)
Difference between ischemia and hypoxia?
Ischemia: deficient blood supply
Hypoxia: deficient oxygen supply
Ischemia leads to nutrition deficiency and of course oxygen deficiency
Then again anaemia can reduce the oxygen transport by the blood and be a reasons as well
what biological function is turn off in ischemia?
Aerobic function is turned off and glycolysis/anaerobic function are turned on (2 ATP instead of 34 ATP per glucose)
What can we see in necrotic cells?
Lipids and fatty acid release leading to calcification of necrotic cells
Difference between reversible and irreversible injury
The reperfusion won’t aid
Reperfusion injury
ROS are produced during hypoxia that then destroy more tissue
Necrosis
Pathological, irreversible cell or tissue death in a living organism
Morphology of necrosis
Swelling: Transport mechanisms that require ATP are not working as intended and the build up of ions lead to increased water uptake
Eosinphilic: more acidic compounds are created e.g. lactate, the mitochondria swell and break leaking lysosomes that break down other parts of the cell leading to neutral and eventual acidic pH in the cytoplasm staining eosine
The ER also swell leading to removal of membranes and clumping of chromatin
Karyorrhexis
Fragmentation of nucleus
Pyknosis
Shrinkage of nucleus
Karyolysis
lysis of nucleus
Irreversible signs
Autolysis, heterolysis, and karyolysis cause by lysosome enzymes
Reversible damage
The nucleus is swollen but still present.
Necrosis at the level of an organ
Infraction
Coagulative necrosis
See a yellow wedge area in e.g. spleen and kidney surrounded by a hyperaemic are due to dilated capillaries. The yellow are neutrophil granulocytes.
Also firm and dry.
Congestion
Reduced outflow leading to hemorrhagic infraction
Double blood supply and infraction
Double blood supply can save the organ, but if not, the area will be red rather than yellow. Lungs and Bowels have double blood supply e.g.
Liquefactive necrosis
Release of enzymes liquifying the organ e.g. brain and pancreas.
Different stroke mechanisms
Infraction and aneurism
Abscess
Typical bacterial infection leading to accumulation of neutrophils that then leave an empty cyst e.g. liver
What forms the brown coloured inside macrophages?
breakdown of haemoglobin to haemosiderin
Caseating necrosis
Granular resembles cheese, don’t see the border of the destructed tissue but you see T cells and other inflammatory cells around the area
Fat necrosis
Damage to organs containing a lot of fat, acute pancreatitis, see tiny soap like lesions with blurred borders
Fibrinoid necrosis
Necrosis of the vessel wall insudated plasma proteins into the vessel wall
Apoptosis
Programmed cell death occurring in normal or pathological individual cells and is regulated by pro and anti apoptotic proteins
2 pathways:
- Intrinsic (mitochondrial) pathway– Bcl-2 family proteins
* Extrinsic (death-receptor) pathway– Fas and Fas-L interactions
Morphology of apoptosis
Cytoplasmic eosinophilic condensation of chromatin Karyorrhexis apoptotic bodies Phagocytosis with inflammatory response
Adaptation of cellular growth and differentiation
atrophy
hypertrophy
hyperplasia
metaplasia
Atrophy
pathological or physiological cellular/organ shrinkage
Physiological atrophy
removal of embryonic structures e.g thyroglossal duct and thymus
Pathological atrophy
ischemia./hypoxia leading to renal atrophy. Short time reversible, longer leads to replacement with fat and connective tissue
Hypertrophy
Enlargement of an organ or tissue due to increase in cell size
e.g. heart and skeletal muscle
physiological atrophy
Working out, uterus enlargement
Pathological hypertrophy
enlargement of heart due to chronic hypertension
Hyperplasia
Enlargement of an organ or tissue due to increase in cell number
Physiological hyperplasia
uterus during pregnancy (both hyperplasia and hypertrophy)
Pathological hyperplasia
imbalance of hormones, inflammation, or following surgical resection e.g. adrenal cortex
Metaplasia
Adaptive process of a tissue characterised by transformation to another type of matured tissue. e.g. bronchial squamous metaplasia due to chronic irritation of the tissue by smoking
Intracellular accumulation
abnormal synthesis/metabolism leads to more product, accumulation of exogenous substances, pigments. E.g. the metabolism isn’t enough and the overload causes damage.
e.g. Excess triglycerides in the liver and inhibition of fatty acid oxidation
Alpha 1 antitrypsin deficiency
accumulation of Tau protein in Alzheimer’s disease, glycogen storage disease in diabetes mellitus
Pigments
Anthracosis (exogenous pigments), Tattoos
Hemosiderin (endogenous pigments)
Amyloidosis
Abnormal accumulation of specific extracellular proteins causing firmness, enlargement and malfunction of the involved organs
associated with chronic and hereditary diseases
can be due to abnormal folding of proteins
Amyloid material
Fibril proteins that bind to proteoglycans glycosaminoglycan and plasma protein diagnosed with Congo red staining
Systemic amyloidosis
chronic inflammation (reactive systemic amyloidosis) hemodialysis
localised amyloidosis
Alzheimer’s diseases, atrial, endocrine amyloid in medullar carcinoma or type 2 diabetes
