Cell Injury Flashcards
Hypoxaemic hypoxia
Arterial content of oxygen is low
- reduced inspired pO2 from atmosphere
- reduced absorption secondary to lung disease
Anaemia hypoxia
Reduced ability of the haemoglobin to carry oxygen e.g. sickle cell anaemia
Carbon monoxide poisoning
Ischaemic hypoxia
Interruption to the blood supply
- heart failure
- blockage of blood supply
Histiocytic hypoxia
Inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes e.g. cyanide poisoning
Time taken for hypoxia in neurones
Few minutes
Time taken for hypoxia in fibroblasts
Few hours
Prolonged hypoxia
- Normally the intracellular free calcium is low but the breakdown of mitochondria and endoplasmic reticulum causes calcium to increase intracellularly
- NCX is reversed and activates enzymes such as ATPases, phospholipase, proteases and endonucleases
- decreases ATP, phospholipids and disrupts the membrane and cytoskeleton proteins and nucleic chromatin damage which is irreversible
When are free radicals produced?
- During normal metabolic reactions such as oxidative phosphorylation
- Oxidative burst in neutrophils
- Radiation converts H20 into OH-
- Fenton reaction - contact with unbound metals within the body e.g. iron and copper
- Drugs and chemicals e.g paracetamol metabolism in the liver
Ceruloplasmin
Storage proteins for copper
How to diagnose cell death
Dye exclusion technique - if the dye enters the cell the cell membrane is permeable therefore the cell is dead
Coagulative necrosis under a microscope
Increased neutrophils
No nucleus in cells
Ghost outlines
Causes of infection other than thrombosis and embolism
Torsion e.g. twisted bowel on mesentery or testicular torsion
Where are white infarcts found
Solid organs such as the heart kidney and spleen
Where are red infarcts found
In the lungs and liver due to a dual blood supply
Intestines due to numerous anastomoses
Tumour lysis syndrome
Killing cancer cells releases potassium which can cause an arrhythmia
Three phases of apoptosis
Initiation
Execution
Degradation and phagocytosis
Initiation of apoptosis
Activation of caspases:
- enzymes that control and mediate apoptosis
- causes cleavage of DNA and proteins of the cytoskeleton
Intrinsic pathway of initiation
- Initiating signal comes from within the cell
Triggered by:
- irreparable DNA damage
- withdrawal of growth factors or hormones
- P53 protein is activated which results in the outer mitochondrial membrane becoming leaky
- cytochrome C is released from the mitochondria, causing activation of caspaces
Extrinsic pathway of initiation
- Initiated by extracellular signals
- triggered by cells in danger e.g. tumour cells or by vitally infected cells
- TNF alpha is secreted by T killer cells and binds to cell membrane receptors (death receptor)
- activates caspaces
Mallory’s hyaline
Damage keratin filaments seen in alcoholic liver disease
Causes of hypercalcaemia
Increased secretion of parathyroid hormone resulting in bone resorption:
- primary - parathyroid hyperplasia or tumour
- secondary - renal failure with increased retention of phosphate
- ectopic - secretion of PTH related proteins by malignant tumours
Destruction of bone tissue
- primary tumours of the bone marrow such as leukaemia or multiple myeloma
- diffuse skeletal metastases
- Paget’s disease - accelerated bone turnover - immobilisation
In a hepatic acinar, which zone is more susceptible to ischaemic damage?
Zone 3 - near the terminal hepatic venue as it’s further away from the portal triad
