Anti thrombotic agents in the endothelium
- plasminogen activators
- prostacyclin
- nitric oxide
- thrombomodulin
General Thrombin Inhibitors
- anti-thrombin III
- α1 antitrypsin
- α2 macroglobulin
- protein C
- protein S
What are the three constituents of Virchow’s Triad?
- abnormalities in blood flow
- abnormalities in blood constituents
- abnormalities of the blood vessel wall
What is the appearance of arterial thrombi?
Pale, granular, lines of zahn (red-rbc, white-wbc), lower cell count.
What is the appearance of a venous thrombi?
Soft, gelatinous, deep red, higher cell count
What are the 5 possible outcomes of thrombosis?
Lysis Propagation Organisation Re-canalisation Embolism
4 types of hypoxia and what they are?
- hypoxaemic hypoxia- arterial O2 contents is low e.g. Altitude or lung disease
- anaemic hypoxia- decreased ability of Haemoglobin to carry oxygen e.g. CO poisoning
- ischaemic hypoxia- interruption to blood supply e.g. Emboli
- histiocytic hypoxia- inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes e.g. Cyanide poisoning
Three free radicals
OH. (Most dangerous)
O2
H2O2
What reaction does superoxide dismutase catalyse ?
O2–> H2O2
It’s an antioxidant reaction.
The three cell changes that can be seen under light microscopy, and the reversible and irreversible changes.
- Cytoplasmic changes- reduced pink staining due to accumulations of water (reversible) then increased pink staining due to detachment of free ribosomes from the ER (irreversible).
- nuclear changes- chromatin clumps (reversible) then pyknosis, shrinkage ; karryohexis, fragmentation; and karryolysis, dissolution of the nucleus (irreversible).
The 4 reversible changes that can be seen under electron microscopy.
- swelling- due to sodium-potassium pump failure
- cytoplasmic bless- due to cell swelling
- clumped chromatin- reduced pH
- ribosome separation from the ER- decreased energy in cells
The 6 irreversible cell changes that can be seen with electron microscopy.
- swelling
- pyknosis, karryolysis, and karryohexis
- rupture of lysosomes
- myelin figures
- ER damage
- amorphous densities in mitochondria
Brief description of caseous necrosis
Microscopically cheesy appearance
Amorphous debris
Infections e.g. TB
Give some key apoptotic molecules (6)
- p53- guardian of the genome (DNA damage)
- cytochrome c, APAF 1, caspase 9- form the apoptosome
- BCL1- prevents cytochrome C release from mitochondria (inhibits apoptosis)
- death ligands e.g. TRAIL
- death receptors e.g. TRAIL-R
- Caspases- effector molecules of apoptosis
What is steatosis?
Abnormal accumulation of triglycerides in a cell. Often seen in the liver.
What is Mallory’s Hyaline?
Damaged protein accumulation seen in hepatocytes in alcoholic liver disease.
What is α1-antitrypsin deficiency and what are the common symptoms.
It is a genetically inherited disorder, the liver produces a version of the protein which is misfolded. It cannot be packaged by the ER and accumulates within it, so can’t be secreted by the liver. The systemic deficiency means that proteases within the lung act unchecked and patients with the condition develop emphysema as lung tissue is broken down.
How is alcohol metabolised?
Steps and enzymes
Ethanol—(1)—>acetaldehyde—(2)—>acetate
- Alcohol dehydrogenase predominantly, also by cytochrome p450 enzyme CYP2E1 and catalase.
- Aldehyde dehydrogenase
In alcohol tolerance, which enzyme has been induced?
CYP2E1
What are the three main effects on the liver of excessive alcohol intake?
- Fatty Changes- steatosis, reversible
- Acute alcoholic hepatitis- metabolites are toxic, usually reversible
- Cirrosis- irreversible and sometimes fatal
How is paracetamol usually detoxified?
Via sulphonation and glucuronidation. Small amounts are metabolised by cytochrome p450 oxidation (CYP2E1) into NAPQI.
What detoxifies NAPQI?
Glutathione
What happens to glutathione in a high dose of paracetamol and why is this important?
Glutathione is used up and NAPQI accumulates. NAPQI is toxic and binds to sulphydryl groups on liver cell membranes causing hepatocyte necrosis and potentially liver failure.
How can an aspirin overdose be fatal?
aspirin stimulates the respiratory centre of the brain which results in respiratory alkalosis. The metabolic acidosis is created to compensate but results in an increase in lactate, pyruvate and ketone bodies–> more acidosis.
