L2 - Cell Injury And Cell Death II Flashcards
Hypoxia and ischaemia overlap but are different, explain
Hypoxia - oxygen deprivation. Can be the result of various things including ischaemia
Ischaemia - an interruption in the blood supply
Describe two causes of hypoxia, you need to know all 4
Hypoxaemic hypoxia (altitude) - arterial oxygen content is low Anaemic hypoxia (anaemia) - decreases ability of the haemoglobin to carry oxygen Ischaemic hypoxia (ischaemia) - interruption of a blood supply Histiocytic hypoxia (cell malfunction_ - inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes (cyanide poisoning)
What can last longer in hypoxic conditions, fibroblasts or neurones?
Fibroblasts
Of the cells components which four regions are most susceptible to injury?
Cell membrane
Nucleus
Proteins
Mitochondria
List two reversible changes that occur from hypoxia cell injury and how they occur
Hypoxia -> decreased oxidative phosphorylation -> decreased ATP production
1) cell swelling and blebbing
2) nuclear clumping
3) ER swelling
4) lipid deposition
List 2 irreversible changes associated with cell injury that can be seen down the microscope
Increases in cell membrane permeability - explanation - calcium comes in and calcifies cell
Nuclues pyknosis or karyolysis or karyorrhexis
ER lysis
rupture of lysosomes
myelin figures
Why are free radicals dangerous?
Because they are extremely reactive due to having an impaired electron in their outer orbit. They are mutagenic and cause production of further free radicals
Name two of the main three most destructive free radicals
Hydroxyl (OH)
Superoxide (O2-)
Hydrogen peroxide (H2O2)
Apart from during normal metabolic reactions name two other times when free radicals are produced
Inflammation
Radiation
Contact with inbound metals in the body
Drugs and other chemicals
Haemachromatosis is a disease in which there are elevated levels of free radicals in the body, what do these patients have too much of in their Body cells?
Iron
Free radicals are reactive oxidative species (ROS) which oxidise molecules, their main targets are lipids in the cell membrane but also proteins, carbohydrates and DNA. They work by ____-linking the molecules and thus mishaping them making them mutagenic
Cross
During times of cell injury cells also give a heat shock response. Heat shock proteins mend unfolded proteins and maintain cell viability, give an example of one
Ubiquitin
Oncosis refers to the swelling and other changes that occur in cells prior to death
Necrosis DOES NOT DESCRIBE CELL DEATH, it describes the changes that occur after a cell has been dead some time. Name the 4 major categories of necrosis
Coagulative
Liquefactive
Caseous
Fat necrosis
Which kind of necrosis occurs as a result of protein denaturation and mainly is the result of ischaemia in solid organs?
Which type of necrosis is the result of enzymes dissolving tissue, has evidence of an inflammatory response and occurs in loose tissues with poor stromal support?
Coagulative
Liquefactive - under the microscope this just looks like nothings there - just a depression
Down the microscope in coagulative necrosis we see ‘____’ outlines of cells with no content in them
Ghost
In caseous necrosis we see structureless debris, give an example of when we would see this
Caseous necrosis is particularly associated with infections.
Tuberculosis in the lungs
What do we see in fat necrosis
Fat deposits that look chalky
What is gangrene
An appearance of necrosis visible to the naked eye
What is an infarct?
Necrosis caused by a reduction of arterial blood flow
What is meant by dry gangrene and what kind of necrosis is it?
What is meant by wet gangrene and what kind of necrosis is it?
Dry - necrosis modified by exposure to air - coagulative necrosis
Wet - necrosis modified by infection - liquefactive necrosis
What is gas gangrene?
A form of wet gangrene where the infection is caused by anaerobic bacteria resulting in palpable bubbles underneath the tissue
What is sepsis?
A condition which arises when the body’s own response to infection causes injury to its own tissues and organs
Give two symptoms of sepsis
Slurring speech of confused Extreme shivering or muscle pain Passed no urine in a day Severely breathless It feels like you're going to die Skin mottled or discoloured/rash
What’s the difference between a thrombus and an embolism?
Thrombus - a blood clot
Embolism - when an obstruction has moves distant to its original site. Can be a thrombus, has bubble, physical material etc
When do white infarcts occur?
When an organ only has one blood supply
Red infarcts are the result of a region having more than one blood supply there is then a haemorrhage into that region even though the tissue is dead. This can happen in ischaemia-reperfusion injury. What is this?
When blood flow is returned to a damaged but not yet necrotic tissue
Give two possible bad consequences of reperfusing a damaged area of tissue
Increased production of free radicals/
Increased delivery of neutrophils resulting in more damage/
Delivery of complement and activation of the complement pathway resulting in further inflammation/
During cell death things can leak out of the membranes too aiding us in diagnosis of the problem. Examples include potassium, enzymes and myoglobin. Which enzyme do we measure for in myocardial infarction?
Troponin I
Necrosis is always pathological. Apoptosis can be pathological but mainly physiological. Give three characteristics that can show us the cell death is apoptotic and not necrotic
- Cell shrinkage
- Organised DNA cleavage
- Membrane integrity is maintained
- Formation of apoptotic bodies (buding rather than blebbing)
- Lysosomal enzymes NOT involved
- NO ASSOCIATED INFLAMMATION
Give an example of when apoptosis occurs a) physiologically b) pathologically
a) embryogenesis in formation of digits) homeostasis/ hormone controlled involutopn
b) Cytotoxic (T killer) cells killing of virally infected cells/when cells are damaged/graft versus host disease
Apoptosis is comprised of an intracellular and extracellular pathway. Briefly describe each
-Intrinsic
Signals from within the cell activate apoptosis
Extrinsic
EC signals like TNFalpha is secreted by T killer cells cause apoptosis
When do abnormal cellular accumulations of water and electrolytes occur?
In cell injury
When do lipids accumulate in the cell (steatosis)? And why?
in the liver. Result of alcohol/untreated diabetes/obesity/toxins
/In xanthoma (yellow patches on skin) - accumulated cholesterol
What is Mallory’s hyaline? When is it seen?
Accumulation of damaged keratin filaments in helatocytes of the liver - seen in alcoholics
Give two other abnormal cellular accumulations apart from water, electrolytes and lipids
Coal in lungs of coal workers/
Alpha 1 antitrypsin accumulation in those with the deficiency/
Tattooing/
Iron deposits in haemachromatosis/
Bilirubin deposits in jaundice (bilirubin is the breakdown product of heme, can’t be excreted due to blocked ducts/
What is dystrophic calcification?
Abnormal deposits of calcium salts in tissues, occurs in areas of dying tissue. Result of increased membrane permeability. Can cause organ dysfunction like calcifying heart valves
Not the result of a problem with calcium metabolism. Normal serum calcium and phosphate levels
What is metastatic calcification
The result of a disturbance in calcium metabolism, increased serum calcium levels -> calcium salt crystals again deposited in regions in body.
What is senescence?
Inability to divide any more, reached maximum number of divisions, result of termites reaching critical length
What can excessive alcohol intake result in
Liver cirrhosis
Fatty deposits on liver
Acute alchohol hepatitis - inflammation of liver
Explanation - remember -itis = inflammation
Give three causes of cell injury and death
hypoxia/trauma/chemicals/microbes/radiation/autoimmunity/dietary problems
Name two causes of hypercalcaemia
Primary - Parathyroid tumour
secondary - renal failure and retention of phosphate
Ectopic - PTH secreting carcinomas like small celll carcinomas
Wide spread tissue destruction e.g. cancer.s
What type of hypoxia would Carbon monoxide poisoning cause?
Anaemic - it binds to haemoglobin ad reduces it’s oxygen carrying abilities
How does apoptosis differ from oncosis?
Shrinkage and chromatin condensation/budding/apoptotic bodies phagocytoed/NOT associated with inflammation/physiological NOT pathological/single cells
In cell injury the Na/K stops working, ion leakage can be worked out from this, T/F?
T
What is cirrhosis?
Replacement of normal functional tissue by scar tissue
