Pathoma - Section 2 - Fundamentals Of Pathology

Front 1

When does injury to a cell/tissue/organ occur?

Back 1

Cellular injury occurs when a stress exceeds the cells' ability to adapt (basic principle). Rather than adapting it will become injured.

Front 2

The likelihood of injury depends on what? Elaborate a bit.

Back 2

• Type of stress
• Severity
(1) If you slowly cut the blood supply (renal artery atherosclerosis) results in atrophy, whereas embolus results in injury.
• Type of cell affected
(1) Neurons are highly susceptible to ischemic injury whereas skeletal muscle is relatively more resistant.

Front 3

Neurons have the ability to withstand hypoxia for ______ to _______ minutes.

Back 3

3 to 5 minutes

Front 4

What is hypoxia?

Back 4

Low/inadequate oxygen delivery to tissue.

Front 5

Hypoxia is a common cause of cellular injury. What are causes of hypoxia?

Back 5

(1) Ischemia
• Decreased blood flow through an organ.
• Can occur with block in arterial flow (e.g. atherosclerosis), or a block in a vein (blocking the flow of fresh blood across the vascular bed in the organ)
• Shock
(2) Hypoxemia
(3) Decreased O2-carrying capacity of blood.
• Anemia.
• CO-poisoning
• Methemoglobinemia

Front 6

Provide an example where a block in a vein would cause ischemia in an organ.

Back 6

Budd-Chiari syndrome. Thrombosis of hepatic vein. The most common cause is polycythemia vera. Another cause of BC syndrome would be a patient with lupus that has lupus-anticoagulant (which creates a hypercoagulable state in that patient).

Front 7

What is shock?

Back 7

Shock is a generalized reduced perfusion of tissue, which results in impaired oxygenation of tissue.

Front 8

What is hypoxemia? Provide examples.

Back 8

Low partial pressure of O2 in the blood (PaO2 < 60 mm Hg, which would translate roughly to a SaO2 < 90%).

FiO2 (% O2 in the atmosphere) → PAO2 (“squeezes” oxygen into capillaries) → PaO2 (“squeezes” oxygen across RBCs) → SaO2 (O2 “squeezed” into Hb)

Examples:
• High altitude: FiO2 is decreased. This decreases PaO2 which decreases PaO2 which result in hypoxemia.
• Anything that increases PACO2 would decrease PAO2. (1) Hypoventilation is an example. (2) COPD is another. (3) Interstitial fibrosis of the lung.

Front 9

You wanted to measure the saturation of oxygen in Hb in RBCs. How would you do this?

Back 9

Pulse oximetry. Identifiex oxy- and deoxyhemoglobin only. It does not idenfity dyshemoglobins.

Front 10

O2 content of blood is calculated how?

Back 10

O2 content = (Hb g/dL x 1.34) x SaO2 + PaO2 x 0.003

Front 11

Provide examples of hypoventilation.

Back 11

Depression of the respiratory center with barbiturates.

Front 12

An SaO2 of ________ produces cyanosis of skin and mucous membranes.

Back 12

< 80%

Front 13

In anemia the PaO2 is ____ (normal/abnormally low) and SaO2 would be (normal/abnormally low).

Back 13

normal; normal

None of these variables are affected:

FiO2 → PAO2 → PaO2 → SaO2

Front 14

Give causes of anemia with examples.

Back 14

(a) Decreased production of Mb (e.g.. iron deficiency)
(b) Increased destruction of RBCs (e.g.. hereditary spherocytosis)
(c) Decreased production of RBCs (e.g.. aplastic anemia)
(d) Increased sequestration of RBCs (e.g., splenomegaly)

Front 15

This is the leading cause of death due to poisoning.

Back 15

CO-poisoning

Front 16

How would the partial pressure of O2 and saturation of hemoglobin be in the case of carbon monoxide poisoning?

Back 16

CO competes with O2 for binding sites on Hb. Decreases SaO2 without affecting PaO2.

Front 17

CO and CN inhibits ___________ in the electron transport chain. Poisoning with these poisons are seen in ____.

Back 17

Cytochrome oxidase; house fires

Front 18

Causes of carbon monoxide poisoning include?

Back 18

(1) Automobile exhaust
(2) Smoke inhalation in house fires
(3) Wood stove (vedkomfyr/vedovn)
(4) Methylene chloride (paint thinner)
(5) Gas heaters

Front 19

From what is cyanide produced in house fires?

Back 19

Combustion of polyurethane products.

Front 20

What are clinical findings in a person with CO poisoning?

Back 20

(1) Cherry-red discoloration of the skin and blood (can be deceptive)
(2) Early sign of exposure is headache
(3) Dyspnea, dizziness (occurs at levels of 20-30%)
(4) Hypoxia causes lactic acidosis
(5) Seizures and coma ensue.

Front 21

A patient is brought in to the ER after having inhaled smoke from a house fire. You ask the patient if he/she has a headache and they reply "yes". What should you be thinking?

Back 21

Early sign of exposure to carbon monoxide.

Front 22

What is the main problem in methemoglobinemia?

Back 22

Iron in heme is oxidized to Fe3+.

Front 23

What happens to the partial pressure of oxygen and saturation of hemoglobin in methemoglobinemia?

Back 23

PaO2 would be normal, SaO2 would be decreased (same as in CO-poisoning)

Front 24

How is methemoglobin regenerated to normal Hb?

Back 24

NADH is used to transfer electrons to cytochrome B5 and cytochrome b5 reductase transfers (e-) to metHb producing normal Hb.

Front 25

Methemoglobinemia is classically seen with ______.

Back 25

Oxidant stresses, such as from sulfa and nitrate drugs.

Front 26

What special group of patients can get a methemoglobinemia?

Back 26

Newborns are particularly at risk for developing methemoglobinemia after oxidant stresses owing to decreased levels of cytochrome b5 reductase until at least 4 months of age.

Front 27

The classic clinical finding in methemoglobinemia is ______?

Back 27

Chocolate-colored blood (increased concentration of deoxyhemoglobin) and cyanosis.

Front 28

Clinically evident cyanosis occurs at metHb levels greater than ______.

Back 28

1.5 g/dL

Front 29

The treatment of methemoglobinemia is ______________.

Back 29

IV Methylene blue. Helps reduce Fe3+ back to Fe2+.

Front 30

How would CO and metHb poisoning occur on an oxygen binding curve?

Back 30

Front 31

Describe the consequences of hypoxic cell injury.

Back 31

1° consequence is decreased ATP, everything else is secondary to that.

• Na+-K+ ATPase is affected, causing cellular swelling.
• Ca++ pump is affected. Increased Ca++ in the cytosol is the "point of no return" for the cell, causing activation of many enzymes.
• Switch to anaerobic glycolysis. Lactic acid production. Denatures structural and enzymatic proteins.

Front 32

If you had to summarize cellular injury in two words, it would be _______________. What would be the consequence on histology for cells in the proximal renal tubule?

Back 32

cellular swelling

Microvilli would be effaced or lost.

Front 33

Cellular swelling would lead to what?

Back 33

(1) Loss of microvilli
(2) Membrane blebbing (membrane "pulls away" from cytoskeleton in certain spots)
(3) Swelling of RER. Would cause ribosomes to detach. Decreased protein synthesis.

Front 34

The hallmark of irreversible injury is __________.

Back 34

membrane damage

Front 35

What membranes are affected in irreversible injury to cells?

Back 35

(1) Plasma membrane
(2) Inner mitochondrial membrane
(3) Lysosomal membrane

Front 36

Agent such as ________ and ________ damage the inner mitochondrial membrane.

Back 36

alcohol; salicylates

Front 37

What is the action of uncouplers?

Back 37

Energy used for synthesizing ATP is used to generate heat. Protons bypass complex 5 in the ETC.

Front 38

Provide an example of a natural uncoupler.

Back 38

Thermogenin in the brown fat of newborns. Thermogenin is useful for stabilizing body temperature in newborns.

Front 39

What is a watershed area?

Back 39

An area between the terminal branches of major arterial blood supplies, and these areas do not have overlapping blood supply.

Front 40

Provide examples of watershed areas.

Back 40

• Area between the distribution of the anterior and middle cerebral arteries.
• Area between the distribution ofthe superior aiul inferior mesenteric arteries (i.e. splenic flexure)

Front 41

Provide some examples of tissues/cells that are susceptible to hypoxic injury.

Back 41

• Subendocardial tissue
• Neurons in cortex, layers 3, 5 and 6.
• Purkinje cells in the cerebellum.
• Hepatocytes around the central vein
• Renal cortex, the straight portion of proximal tubule (highly metabolically active)
• Renal medulla, the Na-K-2Cl cotransport in the thick ascending limb is susceptible to hypoxia.

Front 42

Low ATP causes ________ and _________ to accumulate in the cell, causing activation of the enzyme ___________.

Back 42

citrate; AMP; phosphofructokinase

Front 43

Without ATP, the Na/K-ATPases and sarcoplasmic reticulum __________ fail, leading to increased Na+ and _____ and increased intramitochondrial ________. Failure of sarcoplasmic reticulum to resequester ____ leads to cessation of contraction within ischemic zones of myocardium.

Back 43

Ca+-ATPase; Ca++; Ca++