Chapter 2: Cell Injury

Question 1

Tetralogy of Fallot is a congenital disease of what organ, causing what symptom in the extremities?

Answer 1

Tetralogy of Fallot is a congenital heart disease associated with cyanosis. It involves shunting of venous blood into arterial blood which causes a drop in PaO2.

Question 2

Coronary atherosclerosis, decreased CO and thrombosis of the superior mesenteric vein are all examples of:

Answer 2

ischemia

Question 3

What is respiratory acidosis?

Answer 3

Retention of CO2 in the lungs. This always causes a corresponding decrease in alveolar PO2, which in turn, decreases SaO2 and arterial O2.

Question 4

Name 3 causes of respiratory acidosis.

Answer 4

1. Barbituates –> depression of the medullary respiratory center
2. ALS –> paralysis of the diaphragm
3. Chronic bronchitis

Question 5

Respiratory distress syndrome involves what kind of defect?

Answer 5

RDS involves a diffuse ventilation defect, where a lack of surfactant causes collapse of the airways (atelactasis) in both lungs.

A ventilation defect means the lung is perfused but not ventilated

Question 6

Why are newborns at greater risk for developing methemoglobinemia?

Answer 6

Newborns are at risk for developing methemoglobinemia (Hb with oxidized heme groups, Fe3+) after oxidant stresses until ~4 months, owing to decreased levels of cytochrome b5 reductase, which makes ferrous Fe.

Question 7

Nitrite and/or sulfur-containing drugs, nitrates such as fertilizing agents, and sepsis, can all cause what Hb abnormality?

Answer 7

Methemoglobinemia

Question 8

What are the clinical findings of methemoglobinemia?

Answer 8

Blood is a characteristic brown dolor bc of all the deoxyHb
Cyanosis
Headache, anxiety, tachycardia, dyspnea
Confusion, lethargy, lactic acidosis (anaerobic glycolysis)

Administration of O2 does not relieve cyanosis, as with CO poisoning. Tx is IV methylene blue.

Question 9

Cherry-red discoloration of skin and blood
Headache, dizziness, dyspnea
Seizures, coma
Lactic acidosis

All these are symptoms of:

Answer 9

CO poisoning

Left shift in O2 binding curve

Question 10

Why does high altitude cause a right shift of the O2 binding curve?

Answer 10

Atmospheric pressure is decreased –> hypoxemia stimulates peripheral chemoreceptors –> hyperventilation –> respiratory alkalosis –> increase in intracellular pH –> PFK activated (rate-limiting in glycolysis) –> production of 2,3-BPG –> BPG promotes O2 unloading in tissue.

Question 11

CO and CN specifically inhibit what in the ETC?

Answer 11

CO and CN inhibit the cytochrome oxidase of complex IV of the ETC.

Question 12

CN poisoning most affects the heart and CNS. What are the clinical findings?

Answer 12

Bitter almond smell of breath
Seizures
Coma
Arrhythmias
Cardiovascular collapse

Question 13

Ox phos uncouplers carry protons in the intermembranous space through the inner mito membrane into the matrix without damaging the membrane. The end result is decreased ATP synthesis. What are 2 examples of uncouplers?

Answer 13

1. Thermogenin, natural in newborns for heat production

2. Dinitrophenol, used in making TNT

Question 14

Agents such as alcohol and salicylates are mitochondrial toxins. They damage the inner mitochondrial membrane, causing protons to move into the mito matrix. This may result in what symptom?

Answer 14

Hyperthermia

Dinitrophenol also causes hyperthermia but it is an uncoupler.

Question 15

Coronary artery atherosclerosis and other factors decreasing coronary artery blood flow produce subendocardial ischemia, which manifests as angina and what EKG finding?

Answer 15

ST-segment depression

Question 16

A “watershed” infarction of the brain resulting in a hemorrhage would occur at the junction of what two cerebral arteries?

Answer 16

A watershed infarction in the brain would occur at the junction of the middle and anterior cerebral arteries.

Question 17

What are fibrous caps (or fibrous plaques)?

Answer 17

Fibrous caps are the pathognomonic lesion of atherosclerosis. Oxidized LDL (by free radicals) contributes to the formation of fatty streaks, which are the progenitors of fibrous caps.

Question 18

Why are high doses of acetaminophen toxic to the liver?

Answer 18

In toxic doses, acetaminophen causes diffuse chemical hepatitis due to its conversion by a cytochrome P450 isoenzyme into a toxic intermediate called NAPQ1, a free radical.

Question 19

What free radicals are associated with reperfusion injury?

Answer 19

Superoxide FRs (as well as cytosolic Ca2+ and neutrophils)

Question 20

What is Wilson’s disease?

Answer 20

Copper overload or the inability to excrete copper into the bile
Copper excess in hepatocytes increases the production of hydroxyl FRs

Question 21

What kind of disorders are hemochromatosis and hemosiderosis?

Answer 21

Iron overload disorders, which produce hydroxyl FRs, which lead to cirrhosis and pancreatic dysfunction.

Serum ferritin is increased.

Question 22

Hyperplasia of smooth ER can be seen in what disorder?

Answer 22

Alcoholism
Barbituate use
Phenytoin

Question 23

What is the defect in inclusion (I) cell disease?

Answer 23

I-cell disease is a rare inherited condition in which there is a defect in the modification of lysosomal enzymes in the Golgi. This results in the inability of proteins to be directed into the lysosomes, and large inclusions form in the cell. Symptoms include psychomotor retardation and early death results.

Question 24

When are Mallory bodies found?

Answer 24

Mallory bodies are ubiquinated cytokeratin IFs in hepatocytes, and develop in alcoholic liver disease.

Question 25

What is the defect in CHS, Chediak-Higashi syndrome?

Answer 25

CHS is an autosomal recessive disease with a defect in a lysosomal transport protein, similar but not the same as I-cell disease. These granules in the cell build up and fuse, CHS also involves MT disfunction on neutrophils and monocytes that prevents the fusion of lysosomes and phagosomes, so certain bacteria cannot be cleared from the body such as staph aureus.

Question 26

What is kernicterus?

Answer 26

Rh hemolytic disease in a newborn causes bilirubin (unconjugated) build-up in the basal ganglia, causing permanent damage

Question 27

Yellow plaque on the eyelid due to cholesterol deposited by macrophages is called:

Answer 27

Xanthelasma

Question 28

In diabetes mellitus, there is increased build up of what compound in the proximal renal tubules?

Answer 28

Glycogen

Question 29

What is Von Gierke glycogenosis?

Answer 29

Von Gierke glycogenosis is a deficiency in glucose-6-phosphatase, which causes an increase in G6P, which causes an increase in glycogen being made. Glycogen excess can be found in hepatocytes and renal tubular cells (hepatorenomegaly), both major sites of gluconeogenesis.

Question 30

What is anemia of chronic disease?

Answer 30

During inflammation, the liver releases a protein called hepcidin, which blocks the release of iron from bone marrow macrophages. This causes both an anemia and an increase in serum ferritin, and an increase in hemosiderin within bone marrow macrophages.

Question 31

What causes the hyperpigmentation seen in Addison disease?

Answer 31

Addison disease is an autoimmune attack of the adrenal cortex, leading to hypocortisolism. The hypocortisolism causes an increase in ACTH production, which has melanocyte-stimulating effects including hyperpigmentation (a tan).

Question 32

What is coal worker’s pneumoconiosis?

Answer 32

The phagocytosis of black anthracotic pigment (coal dust) by alveolar macrophages, makes the lung look black.

Question 33

Lead poisoning leads to deposits in what organ?

Answer 33

Kidney, proximal tubules, leading to kidney dysfunction.