Cell Injury Flashcards
What type of cell does paracetamol damage
Liver hepatocytes
Give some causes of cell injury and death (6)
Infection Hypoxia Chemicals & drugs Physical agents ( radiation , trauma) Nutritional factors (dietry insufficiency) Immunological factors
tuberculosis- What category of agent causes this cell injury?
Immunological
Infection
Give an example of a case in which a change in the blood deprives the neurones of a vital nutrient and leads to cell injury.
Hypoglycaemia in blood, and brain gets its nutrients directly from glucose ( if diabetic patient injects too much insulin)
cell can become injured as a result of damage to any of four vital structures:
- Er
- mitochondria
- nucleus
- membranes
What structures would be damaged by taking cyanide? What does it imterfere with
Mitochindra-oxidative phosphorolation
What about hypoxia? Which structure does it damage
Membranes
The point of no return for the cell( irreversible damage) is thought to be marked by influx of a certain ion
Ca+
type of cell death that results from this massive influx of calcium into the cytosol is given a special name.
Necrosis
Whenever there are necrotic cell we find an inflammatory reaction.
Indeed, we can often recognise necrosis because of the inflammation.
Just saying
when the cell membranes break down, an important mediator is formed from the phospholipid that makes up the membrane itself.
What’s this mediator called?
It’s called arachidonic acid.
What is function of arachadonic, how does is mediate inflammation
Arachidonic acid then breaks down into chemicals, ( prostaglandins and leukotrienes) which mediate various components of the acute inflammatory reaction
What term is applied to the changes that occur in the membrane when free radicals damage it
Lipid peroxidation
cell can be digested by its own enzymes? What effect does this have on the cell?
Autolysis, can cause the tissue to become soft.
So infarcts in the heart or brain often become soft.
This makes the tissue liable to break down and even burst.
This time it’s a young woman, who becomes very ill, with nausea and vomiting. She becomes jaundiced and is brought into hospital. She’s thought to have hepatitis. What can be measured
ALT
AST
GT
Explain what happens when cell injury becomes irreversible & how the changes trigger the inflammatory response
The membranes become damaged. The cell membrane damage leads to water influx due to breakdown of the sodium-potassium pump. Calcium also enters the cell.
Calcium also flows out of the mitochondria (mitochondrial permeability transition) and the enzymes there stop functioning. Calcium flows from endoplasmic reticulum and lysosomes into the cytosol, where the level rises very highly.
Phospholipase becomes activated and digests the cell membranes, releasing, among other things, arachidonic acid, which breaks down to form inflammatory mediators, such as prostaglandins and leukotrienes. These attract neutrophils and promote the other aspects of acute inflammation.
Causes of hypoxia can be classified as:
Hypoxemic
Anemic
Ischeamic
Histoxic
What is ischemic reperfusion injury
When blood flow is restored to an “ischemic cell” is restored.
The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of
oxidative stress rather than restoration of normal function.
What are free radicals? How do they cause damage?
Free radicals are reactive oxy species, they have an unpaired electron, and this makes them to want to “steal” an electron from a neighbouring atom.
»attach lipids on membrane»_space; lipid peroxidation
»damage proteins, carb, nucleic acids
Name 3 free radicals
OH hydroxyl(most damage)
02- superoxide
H202 hydrogen peroxide
What r the antioxidant system in our body? and how does each work (3)
Enzymes> neutralise free radicals (catalase, superoxide dismutase, glutathione peroxidse)
Vit A C E
Storage proteins and metal carriers (transferrin) > sequester iron and copper
What are heat shock proteins? how to they function? name some
HSPS, ex: ubiquitin, stress proteins, unfoldases, chaperonins
ta9fee6 il malabis ;P
***They MEND other proteins, so when other proteins r misfolded or damaged as a result of injury, they bind to them and guide them through proper folding
What r the 2 main types of necrosis? And how do they appear on a microscope? give an example of which organ can u see each one?
1) Liquafactive»enzyme release» cant really see shit…Brain
2) Cooagulative»protein denaturation in cell, and clumps> ghost like…kidney
What is gangrene, name 2 types
Necrosis visible to the naked eye
Dry~ exposed to air
Wet~ Liquafactive necrosis
Gas gangrene is wet gangrene w/ infectivd mixed bacterial culture (exudate)
What is an infarction? infarct?
Necrosis caused by reduction in blood supply
an AREA of necrotic tissue which is the result of loss of arterial blood supply.
What is gas gangrene ? Feautures?
Motercycle pic in lecture
caused by ANEROBIC bacteria in soil that enter the wound causes gas gangrene
Feature> palpable bubbles of gas w/ in the tissue
What is caseous necrosis? What does it look like?
Caseous necrotic debris (looks like cottage cheese). MOSTLY IN TB
(Fits in btw coagulative and necrotic)
U get a mess
What r 2 common causes of infarction
Thrombosis
Embolism
Red and white infarction, in which type of organ does each occur in?
White infarction (anaemic)»SOLID organs > in end arteries mostly, no blood supply, often wedge shaped, coagulative necrosis
Red» Infarct complicated by HEMMORHAGE > blood leaks and u becomes read (happens mostly to Loose tissues)
When membranes become leaky, can molecules leak out as well?
Yes
What r the 3 important things that leak out of the cell
Pottasium» leads to cardiac
Enzymes» troponin/AST/Ck
Myoglobin
It takes ________to be able detect the morohological changes in a necrtotic tissue under a light microscope. (Ex MI)
12-24 hrs
What is pathalogical calcification
Abnormal deposition of ca salts in within tissues
In what case do u see lipids accumalating into the cells? Why?
In steatosis (fatty liver) bc that where most fat metabolism occurs
What causes a fatty liver?
- diabetes
- obesity
- alchohol
- toxins
In what clinical conditions to proetins accumalate in cells?
- Emphysema ( lack of a1- antitrypsin ) u get accumaltes of proteases in lung
- alcholoic liver disease (mallorys hyaline) damaged keratin filaments
What is accumalating in jaundince
Bilirubin, (breakdown if heme)
Dystrophic vs metastatic calcification
-Dystrophic is localized ; more common
There is no abnormality in calcium salts, but the disturbance of the tissue favoured deposittion of hydroxyapatite crystals.
-Metastatic (usually asymptomitic but LETHAL)
Hydroxyapetite is laid down due to disturbed calcium metabolism that caused hypercalcemia!
***METAstatic=METAbolism
Blebbing happens in ________
Buddimg happens in________
Necrosis
Apoptosis
What r the 3 steps of apoptosis?
1) initiation
2) execution
3) degredation and phagocytosis
In apoptosis, does the cell shrink or swell?
how do phagocytes recognise them?
Shrink, and form apoptotic bodies, that express proteins on their surfaces, these r recognised by phagocytes.
The plasma membrane in apoptosis is intact/lysed?
Intact
When does fluid accumalate in the cells? In which organ is this a serious problem amd why?
When they get hypoxic, low 02, more na & water flood inside the cell.
In the brain, bc the brain sitsin a restricted area.
What is heridetary haemochromatosis, which organs r mostly effected? how do patients look like? how do u treat it?
Genetically inherited disorder, Increased absorbtion of IRON.
excess iron is deposited as hemosdierin in various organs, skin, (mostly with liver cihrossis and pancreas scarring) .
bc iron is deposited in skin, they look tanned!
-just bleed the patient!!
What r mallory bodies? What causes them
Deposits of clumped abmormal cytoskeletal filaments in hepatocytes
Alchohol
What is karyolysis? pyknosis?
Nucleus just gradually disappeared. This is due to digestion of the DNA in the nucleus by certain enzymes that are released by the injured cell.
is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis.
what enzymes have digested the nuclei to give it this karyolytic appearance?
Enzymes called endonucleases break down the DNA in karyolysis.
___________&___________are the most common types of change we see in the NUCLEUS when the cell dies. If we see these changes, we can say for certain that the cell is dead, deceased, no more: no ifs and buts about it.
Karyolysis & pyknosis
Eosinophilia is an early sign of necrosis. Why does this pink staining occur?
It happens because cytoplasmic proteins become denatured, leading to increased exposure of basic amino acid groups, which react with acidic dyes, such as eosin.
Example of coagulative necrosis would be in
MI
What’s the aetiological mechanism underlying this type of necrosis (colliquative necrosis)?
Hypoxia
In apoptosis, in contrast to necrosis, there’s no inflammatory reaction.
Why is this so?
apoptosis, the bits of dead cell wrapped in plasma membrane So the fragments are never exposed to the extracellular environment and thus aren’t exposed to the immune system.
How do free radicals damage cells
- cause lipid peroxidation
- oxidise proteins (cross-link them), carbs & DNA
What causes hypercalcemia?
- increased secretion of PTH>resulting in bone resorption
- destruction of bone tissue
Oncosis, necrosis, apoptosis
Oncosis» cell death with swelling
Apoptosis» cell death with shrinking
Necrosis» morphological chnages that occur AFTER death
Give a common comdition of fat necrosis in the body
PANCREATITIS
Digestive Enzymes Leak out from pancreas into the abdominal cavity and attack the lipids in the abdomial cavity and break down the triglycerides, and the fatty acids produced will react with calcium forming CA soaps
Or they get into bv and u can detect them
Anastomoses is different than dual blood supply
Dual blood supply, organ is getting blood supply from 2 seperate places (lungs)
Anastomoses, u know it alaa
Graft vs host disease
…
What do injured and dying cells look like jnder a microscope?
- cytoplasmic changes
- Nuclear changes
- cellular accumalations
Why is it bad to suddenly reperfuse an ischemic tissue?
It can lead to ischemic-reperfusion injury,
When u reperfuse highly oxygenated blood to an acidic hypoxic tissue, Its an environment that can produce FREE RADICALS!
Function of igG antibody in infkammation
Most importamt opsonin, not oreseny when bacterium is encountered for the 1st time
Apoptosis
Extrinsic» caspase 8
intrinsic»_space; mitochondra release cytc C,APAF,cas 9
Whats the organelle in the cell is related to intrinsic apoptosis
Mitochondria center
Cytocrome C leaves
And binds to APAF 1 & caspase 9
Which will work on CASPASE 3
In apoptosis what is the convergence point in the cell
Caspase 3
Role lf p53 in apoptosis? BCL-2
BCL-2 is prevents release of cyt C from the mitochondria
Less apoptosis occurs
**If it is over-expressed it causes CANCER
explain in steps what happens during hypoxia
- Cell deprived of oxygen.
- Mitochondrial ATP production stops.
- The ATP-driven membrane ionic pumps run down.
- Na and water seep into the cell.
- The cell swells, and the plasma membrane is stretched.
- Glycolysis enables the cell to limp on for a while.
- The cell initiates a heat-shock (stress) response (see below), which
will probably not be able to cope if the hypoxia persists. - The pH drops as cells produce energy by glycolysis and lactic acid
accumulates. - Calcium enters the cell.
- Calcium activates:
• phospholipases, causing cell membranes to lose phospholipid, • proteases, damaging cytoskeletal structures and attacking
membrane proteins,
• ATPase, causing more loss of ATP,
• endonucleases, causing the nuclear chromatin to clump. - The ER and other organelles swell.
- Enzymes leak out of lysosomes and these enzymes attack
cytoplasmic components. - All cell membranes are damaged and start to show blebbing.
- At some point the cell dies, possibly killed by the burst of a bleb.
what happens if hypoxia is prolonged? what will the increased intracellular Ca+ activate? (4)
damage becomes irreversible.
massive influx of ca+ in cell
Activates enzymes!
- ATPase> less ATP
- Phospholipase>less phospholipids
- Protease>cytoskeletal proteins destroyed
- endonuclease>nuclear chromatin damage
what is an end artery?
any artery that is the sole source of arterial blood to a segment of an organ
what is emphysema?
a type of (COPD) involving damage to the air sacs (alveoli) in the lung.
Smoking»oxidizes a very important methionine chain in A1-ANTITRYPSIN (enzyme responsible to inhibit proteases in the lungs)
what r the 3 enzymes that act as antioxidants? what do these enzymes do?
Enzymes> neutralise free radicals
- catalase
- superoxide dismutase
- glutathione peroxidse)
______necrosis occurs in solid tissues, like the kidneys..
coagulative
intrinsic pathway vs extrinsic pathway in apoptosis?
Intrinsic pathway: signal come inside cell
P53 is activated
causes mitochondrial membrane to become leaky
Cytocrome c is released & activates caspases
Extrinsic pathway: signal comes from bara triggered by tumor cells, virus cells immune cells (t-killer) secrete TNFa bind to 'DEATH recepters" Capases activated!
ur notes alaa.
when do pigments accumalate in cells?
how do these pigments reach peribronchial lymph nodes?
- carbon/coal dust in air
- inhaled and phagocytosed by alveolar macrophages
**alveolar macrophages will migrate from alveoli to the peribronchial lymph nodes and get trapped there
what in anthracosis?
A chronic lung disease resulting from repeated inhalation of coal dust
how does tattoos cause pigmentation? how does this reach the lymph nodes?
pigments is picked up by MACROPHAGES in the dermis and stay there> tattoo stain.
some macrophages will drain in the lymph nodes.
what was once called bronze diabetes? why?
heridetery hemochromatosis,
bronze colour due to deposits of hemosiderin in skin & they used to get diabetes cuz their pancreas was being destroyed.
It what cases can u get increased secretion of PTH? (3)
1) tumour of parathyroid
2) renal failure>retention of phosphate
3) ectopic> secretion of PTH by malignant tumors.
It what cases can u destruction of bone tissue? (4)
1) primary tumor of bone marrow ex: leukaemia, multiple myeloma
2) immobilsation
3) pagets disease> accelerated bone turnover
4) diffuse skeletal metastases
ends of chromosomes r called _____, white every replication the ______is ______.
telomeres= shortened.
when the telomeres reach a certain length, the cell can no longer divide.
wha tis the function of telomerase? which cells have em?
it maintains the original length of telomeres, to make them live longer (ends of chromosomes that shorten within each replication).
GERM CELLS + STEM CELLS
cancer cells too!
which enzymes/proteins will be elevated in the blood and why.
Hepatitis (4)
- Raised serum ALT, AST and LDH. These are cytosolic hepatocellular enzymes and their presence in the blood indicates poor hepatocyte integrity.
- Raised bilirubin (often conjugated) – indicates poor biliary excretory function.
- Decreased albumin, raised PT (reliant on factors 2,7,9,10 produced by the liver),
raised ammonia – these findings indicate poor hepatocyte function.
which enzymes/proteins will be elevated in the blood and why.
· Acute pancreatitis (4)
Raised serum amylase in first 24 hours.
Raised serum lipase from 72-96 hours.
In 10% see glycosuria.
Hypocalcaemia possible – due to precipitation of calcium salts in fat necrosis
what r troponins? when do the peak?
Troponins are proteins that regulate contraction of muscle. They are increased in the blood at 2-4 hours post-MI and peak at 48 hours. They remain elevated for 7-10 days.
you get____ necrosis when theres lots of neutrophils (mostly during inflammation)
liquafactive necrosis
infarct in the brain is healed by____
gliosis
is a nonspecific reactive change of glial cells in response to damage to the central nervous system (CNS)
do u see apoptosis in liver in hepatitis?
yas.
The following would undergo irreversible cell injury within 60 minutes of complete cessation of blood supply? choose
a) myocardium
b) motor neurons
c) skeletal muscle
d) renal tubules
e) chondrocytes
a) myocardium
b) motor neurons
d) renal tubules
Alcoholic liver disease
Acute alcoholic liver disease – a hepatic picture is seen. Chronic alcoholic liver disease – fulminant liver failure is seen.
Raised bilirubin, raised alkaline phosphatase, raised gamma GT (glutamyl transpeptidase). (NB: See raised alkaline phosphatase and gamma GT with damage to bile canaliculus (these are plasma membrane enzymes)).
which enzymes/proteins will be elevated in the blood and why.
-Myocardial infarction
We measure blood levels of intracellular macromolecules that leak out of fatally injured myocardial cells through damaged cell membranes.
Now we measure primarily CARDIAC TROPONIN (TnT), troponin I (TnI), creatine kinase (CK, CK-MB), lactate dehydrogenase (LDH) and myoglobin.
Troponins are proteins that regulate contraction of muscle.
when do Troponins increase in the blood? peak in the blood? how long do they remain for?
They are increased in the blood at 2-4 hours post-MI
PEAK at 48 hrs (2 ays)
They remain elevated for 7-10 days.
When does apoptosis occur normally?
Embyrogeneis
Scultpting
Matamorphosis (butterfly)
When does apoptosis occur normally?
Embyrogeneis
Scultpting
Matamorphosis (butterfly)
