reversible deficiency of blood flow for the metabolic needs of the tissue (4 minutes for brain, 20 minutes for heart, 2 hours for liver).
ischemic death of tissue usually due to arterial occlusion by a blood clot that formed at the site (thrombosis) or traveled there (thromboembolism).
the appearance a dead organ or tissue takes on in a person who remains alive.
programmed cell death, a pathway induced by a tightly regulated intracellular program of activating enzymes that degrade the cell’s own parts.
a localized area of liquefactive necrosis, usually due to acute necrotizing infection, usually best treated by draining the infected liquid.
A single diagnosis that explains all of a patient’s symptoms, signs and other manifestations of disease is most likely the correct diagnosis.
Disease has a spectrum of effects on a person. Define adaptation
set of physiologic and morphologic changes, modulating the function of a person, organ or cell, bringing her or him or it to a new altered steady state of homeostasis, which can usually be sustained indefinitely
What type of disease allows adaptation?
Describe moderate disease wrt adaptation
Moderate disease causes injury because it exceeds the ability to adapt.
the reversible pathophysiologic and morphologic response to a stress or noxious stimulus exceeding the capacity to adapt, but not enough to kill the cell, organ or person.
What disease causes injury too great for a cell, organ or person to survive?
Describe the result of slow chronic loss of small amounts of blood from the gastrointestinal tract causes a person’s blood-making organ, the bone marrow, to adapt and make more blood.
Describe the result to blood loss that is simply too much or too rapid,
the injury to vital organs is irreversible and incompatible with life.
Describe the spectrum from adaptation through injury to death
occurs at the level of tissues (less than a whole organ) and the individual cells that make up tissues and organs.
As a general principle, vital organs have a large reserve capacity
T/F Disease commonly uses up an organ’s reserve capacity silently until it is too late
The same spectrum of response to disease occurs at the level of individual body organs. Describe it wrt blood loss and the kidney
If the blood supply to a kidney becomes inadequate, the kidneys adapts by doing less work. It makes less urine.
If inadequate blood supply to a kidney becomes chronic, it shrinks; this is the process of atrophy.
If the inadequacy of blood supply is too severe, the kidney dies.
Death of an organ is called
Describe the disease process of atherosclerosis
atherosclerosis gradually narrows the lumen of critical blood vessels in the heart
suddenly something (like severe exertion) demands more blood flow than can be delivered
or something (like a blood clot) reduces blood flow below the minimum needed at rest
the person dies suddenly.
Disease causes visible manifestations in what? What is the other name for visible manifestations of disease?
cells, tissues, organs and people
What is the appearance of disease without the aid of a microscope?
What is a term for a discrete visible manifestation of disease?
most commonly used for a well circumscribed visible manifestation of a disease
cause of a disease is commonly referred to as what?
What is normal function?
What is abnormal function, rendered abnormal by disease?
the sequence of events in the response of the person, organ or cell to the etiologic agent of a disease, from the initial stimulus to the ultimate manifestation of the disease
Name the classifications of the categories of disease
1. V for Vascular
2. I for Infectious
3. T for Toxic
4. A for Autoimmune
5. M for Metabolic
6. I (second one) for Idiopathic (to include degenerative)
7. N for Neoplastic
8. D for Developmental (to include genetic)
T/F Inflammation is a classification of the categories of disease
False, it is present in a lot of diseases but not a specific category
Describe what is included in infectious diseases
generally recognized as communicable or transmissible
includes any disease caused by a virus, a bacterium, a prion, a fungus, protozoon or a parasite
Describe the category of toxic diseases
a group of diseases due to a poison, toxin, or other noxious substance, commonly manifesting the symptoms of infection
includes alcohol, radiation injury, natural toxins and therapeutic drugs
Describe autoimmune diseases
those in which the body's immune system causes illness by attacking its own cells, tissues or organs.
- includes systematic lupus erythematosus and rheumatoid arthritis
What is an autonomous growth of cells uncontrolled by the normal controls on cell proliferation (a tumor)?
What is included in the neoplasm classification of disease?
includes benign neoplasms, malignant neoplasms and carcinoma in situ (malignant, but without visible invasion)
What is included in genetic diseases?
nclude autosomal dominant disorders such as polycystic kidney disease, recessive disorders such as cystic fibrosis, and cytogenetic disorders involving autosomes like trisomy 21 and sex chromosomes such as Turner syndrome.
Name the systematic study of disease wrt its divisions
4. Gross Pathology
5. Microscopic Pathology
Describe the 1 and 2 steps of knowing a disease
first step in knowing a disease is having a precise definition of it
next step is knowing the epidemiology of it. The first step in knowing the epidemiology is knowing how common it is
The next step in knowing the epidemiology of a disease is knowing its distribution in different age groups, genders and races.
T/F All diseases occur with different frequencies on the continuum of age and some are unique to a gender, race or ethnic group
Describe the differential Dx of a disease
Once you have settled on a diagnosis, the differential diagnosis refers to everything else that might be the right diagnosis if you are wrong
What are the medically important electrolytes? Name them in order of importance
What electrolyte is important due to abnormal levels impair the heart’s electrical signaling mechanism for the synchronized contraction essential to pumping blood?
What will a decrease in levels of potassium cause?
produce a disturbance in the heart’s signaling rhythm (an arrhythmia, a spelling challenge)
What is the cause to interfere with the contractility of skeletal muscle, causing weakness, myalgias (muscle aches) and fatigue, commonly first symptomatic in the leg muscles?
Hypokalemia also causes what?
hypocontractility of smooth muscle, causing loss of the normal peristalsis (squeezing motion) of the intestines
- resulting mechanical shutdown and dilatation, a condition referred to as ileus or adynamic ileus or paralytic ileus.
Describe a patient with hypokalemia typically presenting with
irritability and develops a rapid heart rate (tachycardia)
More severe hypokalemia may cause respiratory muscle weakness manifested as shallow respirations. Muscle weakness progresses to paralysis. What electrolyte has an imbalance?
What does high potassium or hyperkalemia interfere with? What does it cause?
interferes with muscle function and produces similar
Hyperkalemia causes mental malfunction typically manifested by confusion and nerve malfunction manifested by numbness, tingling and loss of deep tendon reflexes
A patient with hyperkalemia typically has what?
a slow heart rate (bradycardia), progressive muscle weakness, paralysis and then cardiac arrest.
Which is much more likely to cause a fatal cardiac arrhythmia, hypokalemia or hyperkalemia?
What electrolyte is crucial in maintaining the tonicity (osmolality) of the body fluids?
What causes water to enter cells in excess, with resultant cellular swelling?
Low levels of sodium in blood (hyponatremia)
Where is hyponatremia most dangerous?
The swollen brain cells begin malfunctioning.
What are the results of hyponatremia?
This results in confusion, followed by progressive lethargy, obtundation, stupor, coma, seizures and death.
What are the early stages of hyponatremia?
In the early stages of hyponatremia, a patient may experience headache, nausea and malaise
What does high sodium or hypernatremia interfere with?
brain function, leading to confusion, disorientation, progressive lethargy, obtundation and coma.
What does severe hypernatremia do?
depresses the respiratory center in the brain, which supplies the drive to breathe
T/F The lungs do not work w/o stimulus from the brain
What electrolyte is created in the body by renal metabolism?
What is the most important substance in the blood buffering this acid as it is carried to the kidney for excretion?
A deficiency of bicarbonate results in what?
a buildup of acid within the body, acidosis.
What is the most common cause of acidosis? What is the result?
diminishing the body’s ability to get rid of the acid continuously produced by normal metabolism
Other than a deficiency of bicarbonate, describe another cause of excess acid production wrt to anaerobic metabolism
excess acid production due to inadequate oxygen supply to large parts of the body, such as the legs, which makes them resort to anaerobic metabolism, generating lactic acid
Respiratory failure also produces acidosis because of what reason?
the carbon dioxide the lungs fail to excrete as a gas combines with water to form carbonic acid (H2CO3)
T/F Unlike hypokalemia and hyponatremia, acidosis does not have a single distinct clinical syndrome
Respiratory failure leads to what?
Hyperventilation leads to what?
What are the causes of alkalosis? Which one will also deplete potassium?
vomiting => will deplete potassium
Describe how vomiting causes alkalosis
The expulsion of the hydrochloric acid in gastric juice can leave behind an excess of bicarbonate
T/F alkalosis in general and bicarbonate excess in particular do not have distinct clinical syndromes
True - Acidosis does not have a single distinct clinical syndrome.
How is bicarb measured?
estimated on the basis of measurement of a related substance
sample of blood is treated with a strong acid, which breaks down the bicarbonate and liberates its components, including the gas carbon dioxide
This CO2 is measured and reported as a surrogate for bicarbonate.
What are the other sources of CO2? Which could change the reading of bicarbonate?
Other sources include carbonic acid, carbonates and carbamino compounds
carbonic acid is about 5% of this CO2 is normally from carbonic acid and with respiratory failure, this can double.
How would you improve the accuracy of the test for bicarb in the blood?
reduced any excess carbonic acid (due to respiratory failure) by exposing the blood sample to an atmosphere with 40 mm Hg of CO2, the average normal partial pressure of CO2 dissolved in the blood and then reported it as “CO2 combining power” or “alkaline reserve”.
To further improve the surrogacy of the CO2, some medical laboratories have also added oxygen to fully oxygenate the hemoglobin (also a buffer) and run the test at 37 degrees C.
the partial pressure of dissolved CO2 in the blood determined as part of the “blood gases”.
The pCO2 reflects the exhalation of CO2, respiratory function, whereas the bicarbonate reflects the acid-base balance from metabolism.
There are many causes of injury to a person, an organ or a cell. Perhaps the most common is an inadequacy of blood supply, which is termed what?
If the heart stops pumping blood, the person as a whole experiences ischemia, but not for long because why?
total body ischemia soon causes loss of consciousness
If the artery bringing blood to an organ or part of an organ (tissue) is blocked, the result is what?
If ischemia goes on too long, the result is beyond injury; What is the result?
it is the death of the tissue or the organ (termed infarction) or death of the person
Internal organs that are ischemic, but not yet infarcted tend to have what common characteristic?
congested with excess blood in the veins and swollen with fluid leaked from the blood vessels
What is often the earliest gross pathologic change?
a darkening of color
The intestines are normally tan and become brown or red during what disease state?
Describe an ischemic kidney
the medulla (inner portion) becomes congested
- cortex (outer portion) becomes pale
Injured cells release some of their contents into the bloodstream. It is common in muscle but cannot take place in the brain. Why?
The blood brain barrier prevents debris from cerebral ischemia from entering the blood. You will need to do a lumbar puncture.
Blood testing is often used for diagnosing injury what?
Blood testing cannot be done for what organ? Why?
heart, pancreas and liver
- renal cells do not have unique cellular contents like the pancreatic enzymes
- the kidneys are relatively small organs so that a small injury to a larger organ cannot be differentiated from a large injury to the kidneys
How is kidney damage monitored?
Renal injury is diagnosed by monitoring the output of its liquid product and the buildup of waste products in the bloodstream from the failure of renal function
(blood urea nitrogen and creatinine)
Other than the kidney, what other organ besides the kidney does not have a unique cellular contents? How is the damage diagnosed?
lung injury is diagnosed by functional assessment
T/F stomach has some unique cellular contents
What occurs when this happens?
generally pepsin, released into the lumen rather than the bloodstream
The diagnosis of gastric injury is done by what?
causes bleeding into the lumen, so passing a tube through the nose into the stomach (nasogastric intubation) and aspiration of the gastric luminal contents allows detection of gastric injury by assessing the nasogastric aspirate for blood
How can the colon be diagnosed?
colon usually causes bleeding into the lumen (or at least diarrhea) so examining the stool for blood can serve as a screening test for colonic injury
How do you diagnose the small intestine? Which part is usually damaged? Which can be viewed by endoscopy?
jejunum is usually damaged => the difficulty diagnosing injury to the jejunum, it is commonly fatal before it is diagnosed.
duodenum and terminal ileum can be viewed
endoscopy and capsule film,
Amylase is an enzyme that digests carbohydrates. What secrets it?
pancreas and salivary glands
Lipase is an enzyme that digests fats. What organ releases amylase and lipase upon damage?
Describe how alcohol damages the pancreas
alcohol causes inflammation of the pancreas because the release of enzymes designed to digest our hamburger begins digesting us instead.
causes necrosis that elicits an inflammatory response, acute pancreatitis
Even if no physical or radiological damage is seen in the pancreas, how can it be determined if the pancreas is damaged?
elevated amylase and lipase
T/F amylase is excreted in the urine.
small enough to pass through renal glomerulus but amylase can
renal failure causes an increased serum level of amylase
What can be the cause of elevated amylase?
salivary gland inflammation
tumors of lung and ovary
ruptured ectopic pregnancy
Most of the lipase in serum is produced by what? What are secondary secretors of lipase?
Where else is lipase present?
lingual salivary glands, gastric mucosa, intestinal mucosa, pulmonary mucosa
present in leukocytes and adipose tissue cells
Describe acute pancreatitis wrt lipase and amylase
serum lipase levels remain elevated longer than amylase levels, commonly for 8 to 14 days.
90% of patients with acute pancreatitis have elevated levels of amylase and lipase, so these tests have a 90% sensitivity for this diagnosis
40% of patients with elevated lipase do not have acute pancreatitis, so this test is only 60% specific for acute pancreatitis
Spontaneous non-traumatic gas gangrene is usually associated with underlying diseases. What is especially associated?
diabetes mellitus, hematological malignancy and colon cancer
Other than the heart, the organ that uses blood testing to diagnose is what?
What will help diagnose this organ?
leaked hepatocyte contents in the bloodstream for the diagnosis of hepatic injury
The enzymes used to diagnose tissue injury include what?
alanine aminotransferase (ALT),
aspartate aminotransferase (AST),
alkaline phosphatase (ALP or “alk phos”),
lactate dehydrogensase (LDH),
creatine phosphokinase [CPK],
Which enzymes atalyze the interconversion of amino acids? Describe their specificity to the AA
ALT => glutamate and alanine
AST => glutamate and aspartate
T/F Most cells need these transaminases to convert amino acids as needed for making different proteins
false, ALL cells
but different cell types have different amounts of each
T/F Although there is more AST than ALT in hepatocytes, the relative amount of AST is much lower than in other organs
T/F Liver injury is more likely to elevate the ALT out of proportion to the AST than injury to any other organ.
Elevation of the amount of ALT in the blood is more specific for what?
liver injury than elevation of AST
What is the de Ritis ratio and what is normal ratio? Why is it important?
ratio of AST over ALT => ratio of 1.15
sometimes helpful in differentiating among the causes of hepatic injury
Acute hepatic injury will result in what to the de Ritis ratio? Chronic hepatic injury?
acute=> decrease to less than 1
chronic => ratio greater than 1
Many liver diseases cause an elevated level of a key excretory product of the liver. What is this product?
When elevations of AST and ALT are associated with hyperbilirubinemia due to biliary ductal obstruction outside the liver, the de Ritis ratio is generally?
less than 1.5
With intrahepatic biliary obstruction, the ratio is generally?
greater than 1.5
Alcoholic liver disease is associated with a high de Ritis ratio is generally?
range of 2-9
T/F high de Ritis ratio of AST/ALT is adequate to distinguish alcoholic liver disease from the other causes of hepatic injury
false, it is nowhere near
What enzyme is located on the outer cell membranes of nearly all our cell types and functions to transport amino acids into cells?
Why is GGT present more in hepatocytes than any other organ?
hepatocytes have the job of taking in amino acids from the blood carried to them from the intestines (the portal circulation) and making new proteins out of these amino acids
Acute hepatic injury due to viral infection or acetaminophen (Tylenol) overdose causes an elevation in what?
elevation in GGT
much higher elevation in ALT and AST
Diseases causing the backup of bile in the liver (cholestasis) have an elevation of what enzymes? What is a disease that is most present in?
higher levels of GGT than ALT or AST
extrahepatic biliary obstruction
Alcoholic liver disease also causes elevation of what? Why?
elevation of GGT out of proportion to ALT and AST
- alcohol=>potent inducer of GGT synthesis by the hepatocytes
- too much overlap between the levels seen in alcoholic liver disease and other liver diseases for GGT to reliably distinguish them
What is an enzyme made of multiple phosphatases that transfer inorganic phosphate from donor to receptor molecules at an alkaline pH?
Alkaline phosphatase (ALP)
In normal adults, most of the ALP in serum is from what?
liver or bone
Cholestatic liver diseases cause elevated in what?
elevated ALP out of proportion to ALT and AST
T/F Alcoholic liver disease causes less elevation of ALP than GGT
T/F Malignant tumors in the liver cause more elevation of ALP than GGT
What else will show an increase in ALP?
Paget's disease of bone
malignant tumors produce ALP of placental type that gets into the blood to elevate ALP levels
What enzyme catalyzes the conversion of lactate to pyruvate by removing two hydrogens?
lactate dehydrogenase (LDH)
What disease states generally force cells to generate lactic acid?
all sorts of cells generate lactate especially when ischemia or hypoxia forces them to resort to anaerobic energy metabolism
The buildup of lactate is thought to mediate what?
the muscle pain caused by exercise
What causes an increase in LDH?
pulmonary infarction and some pneumonia
Malignant tumors (higher in metastasizing)
hemolysis (breakdown of RBCs)
To diagnose hemolysis, what can LDH be combined with?
LDH combined with tests for haptoglobin (hemoglobin transport protein)
bilirubin (Hg breakdown product)
plasma free hemoglobin
What is ischemic necrosis of an organ or tissue?
What is the appearance a dead organ or tissue takes on in a person who remains alive?
T/F When a person dies, all of the organs and tissues take on a morphology is similar to necrosis
false, it is different from necrosis and referred to as autolysis
What is the difference between necrosis and autolysis?
necrosis elicits an acute inflammatory response under most circumstances, while autolysis does not
What s characterized by a gradual fading of the components of every cell, all at the same rate?
What are infarcts usually due to?
due to occlusion of an artery by a blood clot that formed at the site of occlusion (thrombosis) or traveled there (thromboembolism)
- 99% caused by a clot occluding an artery
Why does an occlusion in a vein rarely cause an infart?
What are the exceptions?
Occlusion of a vein rarely causes infarction because the body has alternative (collateral) pathways for venous outflow from most organs.
- The testes and ovaries are exceptions.
How can the testis and ovary cause an infarction?
Torsion (twisting) of either a testis or an ovary on its pedicle collapses and occludes the thin-walled veins and this creates impedance to arterial inflow
results in infarction if unrelieved
What four factors have an influence on whether reversible ischemia becomes irreversible infarction?
vulnerability of the tissue,
rate of development,
alternative blood supply
What is the most vulnerable organ to ischemia?
Why would a physician prescribe exercise that could cause claudication?
This ischemia is not life-threatening and it causes the growth of collateral arteries, which alleviates the disease.
What are the red hemorrhagic infarcts mechanisms? (3)
dual or anastomosing blood supply
When an ovary twists on its meso-ovarian pedicle (torsion) cutting off the venous outflow, but not the arterial inflow, the result is what?
a red hemorrhagic infarct associated with the sudden onset of extreme abdominal pain
The brain is unique in the way its infarcts evolve. If a cerebral artery is occluded, leading to ischemic necrosis, how does cerebral infarction develop? Why?
ends to develop liquefactive necrosis, that is, the solid tissue turns to liquid and drains away
- a barrier between the inside of the cerebral blood vessels and the cerebral parenchyma, the blood-brain barrier
- Behind the blood-brain barrier, the brain has glial cells that perform the roles of white blood cells.
What cells can transform into debris-eating macrophages within a cerebral infarction and the cells that make collagen and convert infarcts in other organs into scars tend to be excluded by the blood-brain barrier?
What enzyme is released during a myocardial infarction?
Creatine phosphokinase (CPK) or creatine kinase (CK)
What is an enzyme that catalyzes the transfer of phosphate from creatine phosphate to ADP, creating ATP?
What enzyme is generated in muscle and brain? What is it composed of? Describe the difference
CK generated in muscle and brain
composed of M and B dimers
The MB fraction is released into blood with myocardial necrosis (CK-MB) and released after about 3 hours
When is AST released into blood with myocardial necrosis?
starting after 24 hours and peaking 48 hours then normalizing after 4 days
What enzyme is released into the bloodstream with myocardial necrosis after about 24 hours then peaking at 72 hours and normalizing around 7 days?
What are proteins that regulate calcium-mediated contraction of cardiac and skeletal muscle?
Cardiac-specific troponins are released with myocardial necrosis, starting after and peaking when?
Which enzyme is it the same as during a myocardial infarction?
after about 3 hours
peaking around 24 hours
Same as CK-MB
The sensitivity of the troponin level for the diagnosis of acute myocardial infarction improves to something more like 90% if it is assayed when?
10 hours after the onset of chest pain
Why is it recommended to repeat troponin determination at least once, 3-6 hours after the initial level?
to rule in or rule out the diagnosis of acute myocardial infarction
For the diagnosis of acute myocardial infarction, an elevated troponin needs to be combined with at least one of the following?
symptoms of ischemia
electrocardiographic evidence of ischemia
imaging evidence of ischemia
identification of an intracoronary thrombus by angiography or autopsy
What is a distinctive form of ischemic necrosis with blackening and shrinkage, typically of distal extremity, but also sometimes of gallbladder or other internal organs?
What is the treatment of gangrene?
surgery, amputation of the necrotic portion of an extremity or excision of the gangrenous internal organ
What is a distinctive form of necrosis grossly resembling cheese, associated with tuberculosis, histoplasmosis and similar diseases?
T/F Caseating necrosis is not a form of ischemic necrosis
What usually causes caseating necrosis?
fungal infections or infections caused by bacteria resembling fungi (mycobacteria, principal among them Mycobacterium tuberculosis)
What is tissue death with conversion of solid tissue to liquid due to severe acute necrotizing infection, toxicity or (in brain only) ischemia?
What is a localized area of liquefative necrosis. Necrotizing infections are the most common cause of abscesses?
Why aren't antibiotics brought into abscesses by blood vessels?
the blood vessels are destroyed within an abscess
What are the most common cause of abscesses?
What is the usual treatment for an abscess? Why?
Because an abscess is liquid, however, it can be drained away with an aspirating needle and syringe
What is the form of tissue death when fat digested by pancreatic lipase, releases fatty acids, which bind calcium, creating chalky white soap-like material (saponification)?
The type of necrosis determines treatment. What is the Tx for gangrene? caseous necrosis? abscesses?
gangrene => surgery
caseous necrosis => antifungal, antituberculous
abscess => drainage
What is the condensation, shrinkage and hyperbasophilia of a dead cell nucleus? When is this seen?
seen in apoptosis and sometimes necrosis
What is the fragmentation of pyknotic dead nucleus?
What is the fading away of a dead nucleus?
What is a term for the microscopic pathology of the most common form of necrosis because it makes the dead cell look like a tiny condensed fibrin blood clot?
T/F Cells that had died of ischemia do not show it immediately
When do they show it?
Coagulative necrosis of cardiac myocytes=> 4-12 hrs
ischemic necrosis of neurons => 12-24 hrs
a pathway of cell death induced by a tightly regulated intracellular program of activating enzymes
degrade the cell’s own DNA and proteins
programmed cell death
T/F Apoptosis can be either physiologic or pathologic
Describe physiologic apoptosis
occurs in embryogenesis, involution, ending inflammation, and deleting self-reactive lymphocytes
Describe the pathologic apoptosis
occurs in injury due to hypoxia, heat, radiation or chemotherapy, in certain viral diseases, in duct obstruction, transplant rejection and in tumors
Both intrinsic and extrinsic pathways in pathogenesis of apoptosis activate what?
T/F apoptosis is the death of a single cell or clusters of cells. They are retained in an intact cell membrane
What prevents cells undergoing apoptosis to create an inflammatory response?
Apoptosis causes the cell to be targeted for phagocytosis
single mac comes and eats the shrunken apoptotic cell
There is no acute inflammatory (neutrophilic) response
What is the standard blood test for acute myocardial infarction?
troponin blood test