Unit 2 - 2.1-2.4, 2.7 Flashcards
A retrogressive process in which cells deteriorate and show a corresponding and variable degree of functional inhibition, chemical alteration, and morphologic change
cellular injury
What is the sequence of events for cellular injury?
- biochemical alteration
- functional abnormality
- morphological change
What occurs within the cell to a point where the cell with either recuperate or die?
degeneration
What is it called when an injury occurs that the cells can recover from?
subnecrotic or sublethal damage
What happens if necrosis occurs within a small enough area?
the viable neighboring cells will replace the dead ones via proliferation
What happens if the area of necrosis is too large for the cells surrounding it to adapt?
the gap will be replaced with fibrous CT
negative response of the cell to injury
degeneration
Cells have a very limited:
number of responses to injury
4 injury classifications:
- deficiency of a critical material
- lack of cellular energy production
- accumulation of abnormal substances
- physical injury
visible changes
morphologic changes
Why might it be difficult to see morphologic changes?
the cell has to live long enough after the injury for the morphologic change to develop
What system kicks in when the Krebs cycle isn’t working?
anaerobic glycolysis
What is the end product of glycolysis?
lactic acid
Why is a build up of lactic acid bad?
lowers cellular pH and eventually blood pH
How much ATP is yielded from the Kreb’s cycle?
36
How much ATP is yielded from glycolysis?
2
normal blood pH:
7.4
What can occur when the blood pH goes down to 7.0 (acidosis)?
cardiac arrhythmias, CNS dysfunction
What can occur when the blood pH goes up (alkalosis)?
neuromuscular excitability, decreased myocardial contractility, arrhythmias
Why do cells that do a lot of synthesizing have blue staining cytoplasm?
because they have a lot of endoplasmic reticulum
What enzyme is necessary to transport glucose across the cell membrane of hepatocytes, muscle cells, and adipose cells?
insulin
When is insulin not required for glucose transport?
into the brain
characterized by accumulation of lipid within non-adipose cells
fatty change
Where is fatty change most commonly seen? Less commonly?
- liver
- heart and kidney
Gross appearance of fatty change?
tissue is lighter in color (yellow to white); may have a prominent lobular pattern; swollen and friable
List the three reasons fatty acids enter hepatocytes:
- beta-oxidation to produce energy (ATP)
- synthesis of lipoproteins and cholesterol
- synthesis and export of triglycerides (requires phospholipids and proteins)
List the three factors that will lead to the appearance of fat in a cell:
- more fat arrives in the hepatocytes than the hepatocyte can process
- decreased beta-oxidation of fatty acids
- impaired synthesis or release of lipoproteins
What are three ways that can increase the amount of fat entering the hepatocyte past the point that the hepatocyte can process?
- high fat diets
- fat mobilization (anorexia, pregnancy, lactation)
- endocrine issues (esp. diabetes)
What three methods can lead to decreased beta-oxidation of fatty acids?
- hypoxia from anemia or passive congestion
- vitamin deficiencies (niacin, riboflavin)
- toxins that impair mitochrondrial function
What two ways can synthesis or release of lipoproteins be impaired?
- toxins (damage membranes, inhibit protein synthesis)
2. viral infection
generally without physiologic effect unless more severe changes also accompany it
fatty change
List four diseases in which fatty liver is prominent and can be fatal:
- ketosis
- pregnancy toxemia
- hepatic lipidosis and hypoglycemia (toy breed puppies)
- hepatic lipidosis syndrome (cats, ponies, donkeys, and miniature horses)
What is the major source of fat for the liver?
GI tract
What three main tissues use lipids for energy?
heart, skeletal muscle, liver
the process by which fatty acids are broken down in mitochondria to generate Acetyl-CoA:
beta-oxidation
fatty acids cannot be converted into _____________ in animals
glucose
What activates the adipocytes to activate hormone sensitive lipase when blood sugar is low?
glucagon
What happens once hormone sensitive lipase is activated and what does this accomplish?
converts triglycerides into free fatty acids;
the low solubility of free fatty acids allows them to bind to serum albumin and can be transported to muscle and liver for oxidation
What inhibits hormone sensitive lipase?
insulin
What, other than glucagon, can activate hormone sensitive lipase?
stress
metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates
gluconeogensis
What do triglycerides get broken down into once they enter the hepatocytes from the blood?
glycerol and fatty acids
What does beta-oxidation depend on?
oxygen
What is the main source of energy for hepatocytes?
oxidation of fatty acids
What are most fatty acids metabolized to?
phospholipids
Which tissue type synthesizes more triglyceride than the liver?
adipose
What are the two most common causes of hypoxia and thus, decreased beta oxidation of fatty acids?
anemia and central passive congestion
When doing a cross-section of a liver, what is a common way to tell if its morpholigic changed is indicative of fatty liver?
grease/fats left on the knife
What happens if a liver is extremely fatty?
it will float in formalin or water
How would the consistency of a fatty liver feel?
friable; break easily between fingers
What are the bright red areas you can see in yellow livers with very distinct lobular patterns?
blood in the central veins of the hepatic lobules
Where does blood flow to in the liver?
from the portal triad to the central vein
Why are the centrilobular regions of the liver the most vulnerable to hypoxia?
it’s the lowest of any part of the lobule; last in line to receive oxygen
What is the major significance of fatty change
it tells us that we must look for the cause
a condition in which there are excessive ketones (acetoacetic acid and beta-hydroxybutyric acid) in the blood
ketosis
When can ketosis occur in cows?
at peak lactation
When can ketosis occur in sheep and goats?
in late gestation
Why can ketosis occur in pregnant or nursing animals?
high energy expenditure (inadequate quality/intake of food)
How does acetyl-CoA have to enter the Krebs Cycle?
bound to oxaloacetate
What does the liver do to oxaloacetate when carbohydrates are inadequate?
converts it to glucose (via gluconeogenesis)
If all of the oxaloacetate is being converted to glucose, what happens to the acetyl-CoA?
converts it to ketones (which build up in the blood)
Why can’t fat be visualized on a normal histological slide?
tissue gets soaked in xylene which dissolves the fat
How can you visualize fat on a slide?
freeze tissue, then stain with Oil-red-O
What type of dog breed commonly gets hepatic lipidosis?
toy breed dog puppies
Puppies with hepatic lipidosis typically present with what 2 major clinical signs?
neurological signs (due to brain swelling) and cerebral neuronal necrosis (secondary to hypoglycemia)
microvesicular type hepatic lipidosis looks like:
vacuolation consisting of many small vacuoles (as opposed to a few large ones)
a fairly common idiopathic disease that occurs mostly in obese cats following a period of anorexia
hepatic lipidosis
Why is hepatic lipidosis a major problem in cats compared to other animals?
their hepatocytes become dysfunctional when filled with fat
a condition in which the liver fails to remove certain chemicals (especially ammonia and mercaptans) from the portal blood
hepatic encephalopathy
Can cross the blood-brain barrier and is toxic to astrocytes, causing them to swell:
ammonia
thought to act as false neurotransmitters
mercaptans
a purely descriptive term referring to a waxy, homogenous, amorphous, solid, translucent appearance
hyaline degeneration
seen as a hyalinization of collagen - grossly it has a smooth, white, glossy appearance
connective tissue hyaline
describe the microscopic appearance of extracellular hyaline
hyalinized area containing no or relatively few nuclei and stains intensely pink with H&E
What is the effect of connective tissue hyaline in scars?
no effect
What is the effect of connective tissue hyaline in vessel walls?
inelasticity - high blood pressure
What is the effect of depositional hyaline?
interferes with fluid exchange
hyaline materials deposited around cells:
depositional hyaline
What is the significance of tubular casts?
an indication of severe damage to the renal glomerulus, usually due to glomerular amyloidosis or glomerulonephritis
The deposition of a protein especially in the spleen, kidney, and liver. Lymph node and adrenal may be involved:
amyloid extracellular hyaline
What stain placed on the cut surface of an organ with amyloidosis will generally impart a red-brown color?
Lugol’s iodine
Seen especially in kidney tubular epithelium and adrenal cortical cells as small cytoplasmic hyaline droplets
hyaline droplet degeneration
Seen as bright-pink staining globules in the cytoplasm of plasma cells. Seen in chronic diseases or those associated with a hyperammaglobulinemiaL
Russell bodies
may be intranuclear or intracytoplasmic, single or multiple and basophilic or eosinophilic
viral inclusion bodies
seen as a rhomboid, red staining crystal in the nucleus of liver and kidney epithelium of the dog and cat (cause and significance unknown)
crystalline inclusion bodies
Purplish staining, homogenous or concentrically laminated bodies which may occur in the alveoli of the prostate, mammary gland or lung
corpora amylacea
What is the significance of corpora amylacea intracellular hyaline?
may indicate a past inflammatory process
keratin of squamous epithelium that may accumulate excessively in conditions of chronic irritation or altered metabolism
keratohyaline
Where are cytoplasmic inclusions more common?
epithelial cells of the respiratory tract, urinary bladder mucosa, and stomach
What is the name of the inclusion body that is a hallmark for rabies?
Negri bodies
refers to the location of the tumor outside of the bone marrow
extramedullary
Occurs when your bone marrow produces abnormal antibodies that can’t be broken down; deposited in your tissues as amyloid and cannot be broken down
primary amyloidosis (AL)
protein deposits accumulate in one or more organ systems in the body; caused by chronic infection or inflammatory disease
secondary amyloidosis (AA)
Primary protein of AL amyloid is:
serum amyloid A (SAA)
List the common sites for amyloid to occur (5):
kidney, liver, spleen, lymph nodes, and adrenal
What color should normal kidneys be?
mahogany brown
Why is albumin the protein that most often leaks into the nephron?
low molecular weight
What is a consequence of urinating gram quantities of protein at micturition?
weight loss and muscle wasting
combination of generalized edema, ascites, and pleural effusion and hypercholersterolemia secondary to protein losing nephropathy:
nephrotic syndrome
What is the primary way that amyloid causes damage?
compression of normal tissue resulting in ischemia (and often organ failure)
Why is calcium build up a sequelae of necrosis (known as dystrophic calcification)?
regulation of influx of Ca++ into cytoplasm can no longer be controlled; accumulates in the mitochondria
deposition of calcium salts in otherwise normal tissues because of elevated levels of serum calcium
metastatic calcification
Occurs in multiple tissues including liver, pancreas and kidney as an accumulation of glycogen in cytoplasmic vacuoles.
Glycogen infiltration
Describe the gross appearance of organs with glycogen infiltration:
organs may be lighter in color
How does glycogen infiltration appear microscopically?
fuzzy lined vacuoles, single or multiple, in cytoplasm
Where can you see glycogen infiltration in well fed animals?
liver
What does glycogen infiltration affect in poorly controlled DM?
B cells of islets of Langerhands, duct epithelium of the pancreas, renal tubular epithelium
Which two types of tumors often have heavy glycogen infiltration?
seminoma and renal carcinoma
Treating dogs with what drug will increase liver glycogen? What is this called?
corticosteroids; steroid hepatopathy
What disease of horses can cause glycogen infiltration?
polysaccharide storage myopathy
What is the effect of glycogen infiltration?
not harmful but indicates a fault in the metabolism of the cell
What is the form in which glucose is normally stored within hepatocytes in the liver?
glycogen
What is a major metabolic disease affecting glucose metabolism that all of you are familiar with?
DM
What color does PAS stain glycogen?
magenta
Glucocorticoids are often induced by:
stress
reduction in mass of a tissue or organ
atrophy
increase in the size of cells, resulting in enlargement or rogans
hypertrophy
increased number of cells in an organ or tissue
hyperplasia
transformation or replacement of one adult cell type with another
metaplasia
any change that results in loss of the ability to maintain the normal or adapted homeostatic state
cell injury
Hallmarks of Cell Degeneration:
cell swelling, fatty change, glycogen accumulation, lipofuscin, hyaline changes, amyloid, calcification, gout
A complex protein that accumulates within cells; homogeneous pink materal
amyloid
more common in birds and reptiles, but can occur in other species (assoc. with renal dz due to decreased excretion of urates)
gout
accumulation of lipid (TG) within vacuoles within cells
fatty change
the oxidized products from membrane lipids (yellow to brown)
lipofuscin
dense, homogenous, glossy, translucent; many causes (protein leak most common)
hyaline changes
no nuclear displacement with:
glycogen accumulation
What are the three pathogeneses for fatty change?
overload, injury to cells, deficiencies
What are the three pathogenic mechanisms for glycogen accumulation?
- severe hyperglycemia
- high glucocorticoids
- lysosomal storage disease
cytoplasm contains rounded, eosinophilic droplets, vacuoles, or aggregates
hyaline droplets
protein casts within renal tubules
hyaline casts
compacted collagen, scar tissue
CT hyaline
Describe the gross appearance of calcification:
chalky, white tissue; hard, gritty on cut surface
Describe the gross appearance of amyloid:
enlarged, pale, waxy, translucent
Has dark blue staining material, along BM, stippled throughout cell, large clumps. What is this the microscopic appearance of?
calcification
Widespread excessive calcification:
calcinosis
What is the term used for calcification in the cavities or lumina?
calculi/calculus
Accumulation or urate crystals
gout
White, firm, crystal depsoits on gross appearance:
gout
Granulomas with radiating crystalline material on microscopic appearance:
gout
What is the most common action for toxins?
free radicals
