Flashcards in Pathology 2 - Cell Injury Deck (55):
What is the difference between hypoxia and ischaemia?
Hypoxia - decreased OXYGEN supply to certain cells/tissues
Ischaemia - decreased BLOOD supply to certain cells/tissues
What are the four main causes of hypoxia?
1) HYPOXAEMIC - arterial content of oxygen is low (causes: being at altitude, or reduced absorption due to lung disease)
2) ANAEMIC - decreased ability of Hb to carry oxygen (causes: anaemia or CO poisoning)
3) ISCHAEMIC - interruption to blood supply (causes: blockage of vessel, heart failure)
4) HISTIOCYTIC - can't use O2 in cells due to disabled oxidative phosphorylation enzymes (causes: cyanide poisoning)
True or false - hypoxia affects all cells at the same rate?
False - neurones are affected within a few minutes, but fibroblasts take a few hours to be affected.
What is a hypersensitivity reaction?
Host tissue is injured secondary to an overly vigorous immune reaction, eg. Urticaria
What is an autoimmune reaction?
Immune system fails to distinguish self from non-self
Describe how ischaemia leads to decreased pH
- decreased oxidative phosphorylation due to lack of oxygen
- decreased ATP as aerobic respiration cannot continue
- anaerobic respiration takes over which produces lactate and lowers pH
What are free radicals?
A reactive species with a single unpaired electron in an outer orbit. It can react with other molecules, producing further free radicals
How are free radicals produced in the body?
- normal metabolic reactions
- contact with unbound iron and copper
- drugs and chemicals
Give some ways that the body controls free radicals.
- antioxidant system (vitamins A, C and E) donate electrons to the free radical
- metal carrier/storage proteins sequester iron and copper
- enzymes neutralise free radicals
Give some examples of enzymes that neutralise free radicals
- superoxide dismutase
- glutathione peroxidase
What is oxidative imbalance?
Occurs when the number of free radicals overwhelms the anti-oxidant system
What do free radicals injure within cells?
- lipids, by causing lipid peroxidation which leads to generation of further free radicals
- proteins, carbohydrates and DNA by altering their structure (bent out of shape, broken or cross-linked), which causes them to become mutagenic and carcinogenic
What are heat shock proteins?
Proteins that 'mend' mis-folded proteins and maintain cell viability by binding to other proteins and guiding through the process of refolding correctly
Why does the cytoplasm appear more pink (with H&E staining) when the cell dies?
Proteins clot in the cytoplasm
Why does dispersion of ribosomes occur during hypoxia?
Ribosome adherence to the ER is an active process, so if the ATP runs out then ribosomes will detach from the ER.
How can cell death be diagnosed on a microscope slide?
Put cells in fluid with fluorescent dye, if cells have holes in their membranes (and therefore are dead) then the dye will go into the cells. If not, they will exclude it.
What are the two main types of necrosis?
Coagulative (related to protein denaturation) and liquefactive (related to enzyme release)
What is the difference in appearance of cells in coagulation necrosis vs liquefactive necrosis?
In coagulation necrosis the cellular architecture is mostly preserved, but in liquefactive necrosis it is almost entirely digested
What is caseous necrosis?
A form of cell death in which the tissue maintains a cheese-like appearance, characteristic of tuberculosis
What is fat necrosis?
Occurs when the enzyme lipase releases fatty acids from triglycerides. The fatty acids complex with calcium to form soaps, which appear as white chalky deposits.
What is gangrene?
Necrosis visible to the naked eye
What is an infarct?
An area of necrotic tissue which is the result of loss of arterial blood supply
What is the difference between dry and wet gangrene?
Dry gangrene = necrosis modified by exposure to air (coagulative)
Wet gangrene = necrosis modified by infection (liquefactive)
What is gas gangrene?
Wet gangrene where the infectious bacteria are anaerobic and produce gas. This is life threatening and moves extremely quickly.
Why are some infarcts red rather than white?
- occur in loose tissue with dual blood supply
- numerous anastomoses
- prior congestion with blood
- raised venous pressure
Give some examples of things that can leak out of cells following cellular injury
What is apoptosis?
Cell death with shrinkage, induced by a regulated intracellular program where a cell activates enzymes that degrade its own nuclear DNA and proteins
Are lysosomal enzymes involved in apoptosis?
Give some examples of when apoptosis occurs physiologically
- hormone controlled involution
- generally to maintain a steady state
Give some examples of when apoptosis may occur pathologically
- cytotoxic T cell killing of virus-infected or neoplastic cells
- when cells are damaged, particularly when DNA is affected
- graft versus host disease (occurs after bone marrow transplant)
What are the three phases of apoptosis?
- degradation and phagocytosis
What are caspases?
Enzymes that control and mediate apoptosis and cause cleavage of DNA and proteins of the cytoskeleton
Give some triggers of the intrinsic pathway of apoptosis
- irreparable DNA damage
- withdrawal of growth factors/hormones
How is the intrinsic pathway of apoptosis carried out?
- p53 protein is activated which results in outer mitochondrial membrane becoming leaky
- cytochrome C is released from the mitochondria which causes activation of caspases
How is the extrinsic pathway of apoptosis carried out?
- triggered by cells that are a danger eg tumour or virus-infected cells
- initiated by extracellular signals eg TNF alpha
- TNP alpha is secreted by T killer cells and binds to the cell membrane receptor, resulting in the activation of caspases
How are apoptotic bodies disposed of?
They express proteins on their surface, so they can be recognised by phagocytes which engulf and degrade them
What is the difference between budding and blebbing?
Budding is when small parts of the cell break off in apoptosis. Blebbing is when parts of the cell swell out of a disruption in the cell membrane in necrosis.
What are the five main groups of intracellular accumulations?
1) water and electrolytes
Why is hydropic swelling a particular problem in the brain?
If the brain swells, there is nowhere for the pressure to go
What is steatosis?
A accumulation of triglycerides in cells (often in liver) due to alcohol/diabetes mellitus/obesity/toxins
How do lipids accumulate in cells?
- Cholesterol cannot be broken down and is insoluble so must be eliminated via the liver.
- Excess is stored in cell in vesicles.
- Also accumulates in smooth muscle and macrophages in atherosclerotic plaques.
- Present in macrophages in skin and tendons of people with hereditary hyperlipidaemias
How does alpha-1 antitrypsin deficiency lead to accumulation of proteins in the cells?
- liver produces incorrectly folded alpha-1 antitrypsin protein
- cannot be packaged by ER, accumulates within ER and is not secreted
- in systemic deficiency, proteases act unchecked in the lung resulting in emphysema
Give examples of exogenous pigments which could accumulate in the skin
- carbon, coal, dust or soot (urban air pollutants)
What is haemosiderin?
Iron storage molecule derived from haemoglobin. It is deposited in organs with a systemic overload of iron
What is hereditary haemochromatosis?
Genetically inherited disorder which results in increased intestinal absorption of dietary iron. It is deposited in skin, liver, pancreas, heart and endocrine organs, with symptoms of liver damage, heart dysfunction and multiple endocrine failures.
How is hereditary haemochromatosis treated?
What causes the yellow colour of jaundice?
Accumulation of yellow bilirubin
How is bilirubin usually removed from the body?
It is conjugated in liver and excreted in bile
What are the four mechanisms of intracellular accumulations?
- abnormal metabolism
- alterations in protein folding and transport
- deficiency of critical enzymes
- inability to degrade phagocytosed particles
What is calcification of tissues?
Abnormal deposition of calcium salts within tissues. Can be localised (dystrophic) or generalised (metastatic).
Why does dystrophic calcification occur?
Local change/disturbance favours nucleation of hydroxyapatite crystals
Why does metastatic calcification occur?
Due to hypercalcaemia secondary to disturbances in calcium metabolism
What causes hypercalcaemia?
- increased secretion of parathyroid hormone resulting in bone resorption
- destruction of bone tissue
Give some causes of destruction of bone tissue
- primary tumours of bone marrow
- diffuse skeletal metastases
- Paget's disease of bone