Cellular Reaction to Injury

What is the cause of metastaic calcification?

(1) Hyperparathyroidism (2) Osteolytic tumors with resultant mobilization of calcium and phosphorus (3) Hypervitaminosis D (4) Excess calcium intake, such as in the milk-alkali syndrome (nephrocalcinosis and renal stones caused by milk and antacid self-therapy)

What are the myocardial enzymes in serum useful to diagnose an MI?

(a) Lactate dehydrogenase (LDH) (b) Creatine kinase (CK, also known as CPK) (c) Aspartate aminotransferase (AST, previously known as serum glutamic oxaloacetic transaminase) has been used in the past but has fallen out of favor due to poor sensitivity for myocardial infarction. The foregoing enzymes are beginning to be replaced by other myocardial proteins in serum as indicators of myocardial necrosis. Important examples include the troponins (troponin I and troponin T) and myoglobin.

What is myeloid metaplasia?

(extramedullary hematopoiesis) is proliferation of hematopoietic tissue at sites other than the bone marrow, such as the liver and spleen.

What does the decreased ATP cause in cells?

1) Failure of cell membrane pump 2) Swelling of ER 3) Swelling of the mitochondria

What are the intracellular mechanisms that degrade free radicals?

1) Glutathione 2) Peroxidase 3) Suproxide Dismutase

What are reversible signs of damage?

1) Myelin figures, whorl-like structures, probably originating from damaged membranes 2) Cell blebs, a cell surface deformity, most likely caused by disorderly function of the cellular cytoskeleton

What are exogenous and endogenous antioxidants?

1) Vitamin A 2) Vitamin C 3) Vitamin E 3) Cystein, Gluthione, Selenium, Ceruloplasmin, and transferrin

What causes fatty change?

1) increase Tg or FA transport 2) Decreased mobilization of fat 3) Decreased use of fat cells 4) Overproduction of fat in cells

What are the mechanisms that generate free radicals?

1) normal metabolism 2) oxygen toxicity (respiratory distress syndrome, ocular disorders) 3) ionizing radiation 4) UV light 5) Drugs and chemicals, look for proliferation and hypertrophy of smooth ER in liver 6) Reperfusion injury

What squamous metaplasia?

1)exemplified by the replacement of columnar epithelium at the squamocolumnar junction of the cervix by squamous epithelium. 2) It can also occur in the respiratory epithelium of the bronchus, in the endometrium, and in the pancreatic ducts.

What are free radicals?

1. These molecules have a single unpaired electron in the outer orbital. 2. Examples include the activated products of oxygen reduction, such as the superoxide and hydroxide

What is hyaline change?

1. This term denotes a characteristic (homogeneous, glassy, and eosinophilic) appearance in hematoxylin and eosin sections. 2. It is caused most often by nonspecific accumulations of proteinaceous material.

5. A 29-year-old man hospitalized for acquired immunodeficiency syndrome (AIDS) is found to have pulmonary tuberculosis. Which type of necrosis is found in the granulomatous lesions (clusters of modified macrophages) characteristic of this increasingly frequent complication of AIDS? (A) Caseous (B) Coagulative (C) Enzymatic (D) Fibrinoid (E) Liquefactive

A Caseous necrosis occurs as part of granulomatous inflammation, typified by the lesions of tuberculosis

2. A 16-year-old girl undergoes radiologic imaging of her abdomen and is found to have only one kidney. She had been entirely unaware of this problem. Which of the following terms is most descriptive of this finding? (A) Agenesis (B) Atrophy (C) Hyperplasia (D) Hypoplasia (E) Metaplasia

A The patient has renal agenesis, absence of the kidney due to failure of organ development. The congenital lack of one kidney differs from atrophy, in which a decrease in the size of an organ results from a decrease in the mass of preexisting cells. Unilateral renal agenesis is usually a harmless malformation, and the opposite kidney is often enlarged due to compensatory hypertrophy. Bilateral renal agenesis is incompatible with life and is of special interest since it can lead to the Potter progression (see Chapter 17).

9. A 20-year-old man presents with yellowing of the sclerae, skin, and oral mucosa. Which of the following accumulations underlies these findings? (A) Bilirubin (B) Hemosiderin (C) Lead (D) Melanin (E) Silver

A Yellowing of the sclerae, skin, and oral mucosa are all characteristic of jaundice, the accumulation of bilirubin, the catabolic product of the heme moiety of hemoglobin. Jaundice can occur by diverse mechanisms: hemolytic (see Chapter 11), hepatocellular (see Chapter 16), or obstructive (see Chapter 16).

What are the characterisitics of hypertrophy?

A cellular adaptation to increased workload results in hypertrophy, as exemplified by the increase in skeletal muscle mass associated with exercise and the enlargement of the left ventricle in hypertensive heart disease. Other characteristics include an increase in protein synthesis and an increase in the size or number of intracellular organelles.

11. The illustration is from a liver biopsy of a 34-year-old woman with a long history of alcoholism. Which of the following is the best explanation for the changes shown here (A) Accumulation of triglycerides within hepatocytes (B) Apoptosis with replacement of damaged cells by lipid-laden macrophages (C) Bilirubin accumulation with mobilization of fat by bile salts (D) Enzymatic fat necrosis with digestion of liver parenchyma by released enzymes (E) Irreversible damage to mitochondria

AThe figure illustrates fatty change of the liver, which is characterized by the accumulation of intracellular parenchymal triglycerides. It is seen most frequently in the liver, heart, and kidney and is commonly secondary to alcoholism. Fatty change results from an imbalance between the uptake, utilization, and mobilization of fat from liver cells. Alcoholic fatty liver may be reversible with complete abstinence from alcohol.

What is aplasia?

Aplasia is a failure of cell production.

What is squamous metaplasia associated with?

Associated conditions include chronic irritation (e.g., squamous metaplasia of the bronchi with long-term use of tobacco) and vitamin A deficiency.

What is atrophy?

Atrophy is a decrease in the size of an organ or tissue and results from a decrease in the mass of preexisting cells

12. A 45-year-old man is referred because of a recent diagnosis of hereditary hemochromatosis. Which of the following is a correct statement about this disorder? (A) Damage to organs results from abnormal deposition of lead (B) It can progress to liver cirrhosis, diabetes mellitus, and skin pigmentation (C) Most cases are due to spontaneous mutations (D) Skin hyperpigmentation is due to bilirubin accumulation (E) The TIBC is characteristically increased

B 12. The answer is B. In advanced form, primary (hereditary) hemochromatosis is characterized by the triad of cirrhosis, diabetes, and hyperpigmentation, or so-called bronze diabetes. The disease is most often caused by a mutation in the Hfe gene on chromosome 6 and is characteristically familial rather than sporadic. The manifestations of the disorder are the result of iron overload and deposition of hemosiderin in tissues such as the liver, pancreas, skin, joints, and pituitary. Laboratory abnormalities of note include increased serum iron and decreased TIBC. The skin hyperpigmentation is due largely to increases in melanin and to lesser accumulations of hemosiderin

6. A 45-year-old woman is investigated for hypertension and is found to have enlargement of the left kidney. The right kidney is smaller than normal. Contrast studies reveal stenosis of the right renal artery. The size change in the right kidney is an example of which of the following adaptive changes? (A) Aplasia (B) Atrophy (C) Hyperplasia (D) Hypertrophy (E) Metaplasia

B The decreased size is due to restriction of the blood supply, one of the causes of atrophy. The increase in size of the opposite kidney is referred to as compensatory hypertrophy. Unilateral renal artery stenosis is a well-known cause of secondary hypertension. In this setting, increased renin excretion and stimulation of the renin- angiotensin system results in a form of hypertension that is potentially curable by surgical correction of the underlying vascular abnormality.

10. This figure illustrates the microscopic appearance of the heart of a 56-year-old man who died after a 24-hour hospitalization for severe "crushing" chest pain complicated by hypotension and pulmonary edema. The type of necrosis shown is best described as (A) caseous. (B) coagulative. (C) fibrinoid. (D) gangrenous. (E) liquefactive

B The figure illustrates general preservation of myocardial architecture with some fragmentation, more intense cytoplasmic staining corresponding to increased cellular eosinophilia, and loss of nuclei, all of which are characteristics of coagulative necrosis.

4. A 45-year-old man with a long history of alcoholism presents with severe epigastric pain, nausea, vomiting, fever, and an increase in serum amylase. During a previous hospitalization for a similar episode, computed tomography scanning demonstrated calcifications in the pancreas. A diagnosis of acute pancreatitis superimposed on chronic pancreatitis was made. In this condition, which of the following types of necrosis is most characteristic? (A) Caseous (B) Coagulative (C) Enzymatic (D) Fibrinoid (E) Liquefactive

C Pancreatic enzymatic fat necrosis represents autodigestion by proteolytic and lipolytic enzymes released from damaged parenchymal cells of the pancreas. Fatty acids liberated by the digestion of fat form calcium soaps, a process referred to as saponification. The precipitated calcium in the soaps can be visualized by radiologic imaging.

What two types of necrosis does caseous necrosis combine?

Caseous necrosis combines features of both coagulative necrosis and liquefactive necrosis. On gross examination, caseous necrosis has a cheese-like (caseous) consistency

What causes coagulative necrosis?

Coagulative necrosis results most often from a sudden cutoff of blood supply to an organ (ischemia), particularly the heart and kidney. HEART and KIDNEY

13. A 60-year-old woman with breast cancer and widespread bony metastases is found to have calcification of multiple organs. The calcifications are best described as (A) dystrophic with decreased serum calcium. (B) dystrophic with increased serum calcium. (C) metastatic with decreased serum calcium. (D) metastatic with increased serum

D 13. The answer is D. Metastatic calcification, or deposition of calcium in previously normal tissue, is caused by hypercalcemia. In this patient, tumor metastases to the bone with increased osteolytic activity caused mobilization of calcium and phosphate, resulting in hypercalcemia. Metastatic calcification should be contrasted with dystrophic calcification, in which the serum calcium concentration is normal and previously damaged tissues are the sites of deposition.

1. The illustration shows a section of the heart from a 45-year-old African-American man with long-standing hypertension who died of a "stroke." Which of the following adaptive changes is exemplified in the (A) Aplasia (B) Atrophy (C) Hyperplasia (D) Hypertrophy (E) Hypoplasia

D The illustration shows marked hypertrophy of the left ventricle. Hypertrophy of this extent, often seen in hypertensive heart disease, is caused by increased workload from increased ventricular pressure. This organ enlargement is the result of an increase in size of the individual muscle cells.

7. A 56-year-old man recovered from a myocardial infarction after his myocardium was entirely "saved" by immediate thrombolytic therapy. If it had been possible to examine microscopic sections of his heart during his ischemic episode, which of the following would be the most likely cellular change to be found? (A) Karyolysis (B) Karyorrhexis (C) Pyknosis (D) Swelling of the endoplasmic reticulum

D If infarction is averted by immediate thrombolytic therapy, indicators of necrosis, such as karyorrhexis, pyknosis, and karyolysis, which represent irreversible changes, would not be expected. Swelling of the endoplasmic reticulum from increased cell water, one of the earliest ultrastructural changes observed in injured cells, is reversible and would be expected.

What is an example of aplasia?

During fetal development, aplasia results in agenesis, or absence of an organ due to failure of production. Later in life, it can be caused by permanent loss of precursor cells in proliferative tissues, such as the bone marrow.

What is dystrophic calcification?

Dystrophic calcification is defined as calcification in previously damaged tissue, such as areas of old trauma, tuberculosis lesions, scarred heart valves, and atherosclerotic lesions (Figure 1-5).

14. A 56-year-old man dies 24 hours after the onset of substernal chest pain radiating down his left arm to the ulnar aspect of his fingertips. Which of the following morphologic myocardial findings is an indicator of irreversible injury? (A) Cell blebs (B) Depletion of glycogen (C) Mitochondrial swelling (D) Myelin figures (E) Pyknotic nuclei

E 14. The answer is E. Myelin figures, cell blebs, mitochondrial swelling, and glycogen depletion are all signs of reversible injury. Nuclear changes such as pyknosis, karyorrhexis, and karyolysis are signs of cell death and are, of course, irreversible.

8. A 64-year-old woman presents with fever, chills, headache, neck stiffness, vomiting, and confusion. The Kernig sign (passive knee extension eliciting neck pain) and Brudzinski sign (passive neck flexion eliciting bilateral hip flexion) are both positive. Examination of the cerebrospinal fluid reveals changes consistent with bacterial meningitis, and brain imaging demonstrates a localized abscess. Which of the following types of necrosis is most characteristic of abscess formation? (A) Caseous (B) Coagulative (C) Enzymatic (D) Fibrinoid (E) Liquefactive

E Liquefactive necrosis is characteristic of ischemic injury in the CNS and suppurative infections that cause abscess formation (see Chapter 2). The changes in the cerebrospinal spinal fluid characteristic of bacterial meningitis are detailed in Chapter 3.

3. An impending myocardial infarction was successfully averted by thrombolytic (clot-dissolving) therapy in a 55-year-old man. Which of the following biochemical events most likely occurred during the period of hypoxia? (A) Decreased hydrogen ion concentration (B) Increase in oxidative phosphorylation (C) Loss of intracellular Na+ and water (D) Stimulation of ATP synthesis (E) Stimulation of anaerobic glycolysis and glycogenolysis

E The sequence of events in hypoxic cell damage is as follows: Hypoxia results in failure of oxidative phosphorylation, with resultant depletion of ATP and increase in adenosine monophosphate and adenosine diphosphate. Anaerobic glycolysis and glycogenolysis are stimulated (not inhibited) through increased phosphofructokinase and phosphorylase activities, respectively. This results in an accumulation of cell lactate, with a decrease in intracellular pH and depletion of cellular glycogen stores. Decreased availability of ATP also results in failure of the Na+K+-ATPase pump, which then leads to increased cell Na+ and water and decreased cell K+

What is enzymatic at necrosis?

Enzymatic fat necrosis, which is a complication of acute hemorrhagic pancreatitis, a severe inflammatory disorder of the pancreas (1) Proteolytic and lipolytic pancreatic enzymes diffuse into inflamed tissue and literally digest the parenchyma. (2) Fatty acids liberated by the digestion of fat form calcium salts (saponification, or soap formation). (3) Vessels are eroded, with resultant hemorrhage.

What are the pathologic chanes in coagulativ necrosis?

General preservation of tissue architecture is characteristic in the early stages. Increased cytoplasmic eosinophilia occurs because of protein denaturation and loss of cytoplasmic RNA.

In what diseases do we see jaundice?

Hemolyic jaundice destruction of red cells causing yellow bilirubin pigments hepatocellular jaundice parenchymal liver damage and obstructive jaundice

What is hyperplasia?

Hyperplasia is an increase in the size of an organ or tissue caused by an increase in the number of cells.

What is hypertrophy?

Hypertrophy is an increase in the size of an organ or tissue due to an increase in the size of cells.

What is hypoplasia?

Hypoplasia is a decrease in cell production that is less extreme than in aplasia.

What are late stage signs of hypoxic damage?

Hypoxic cell injury eventually results in membrane damage to plasma and to lysosomal and other organelle membranes, with loss of membrane phospholipids.

What area of the cell does hypoxic injury first affect?

Hypoxic cell injury first affects the mitochondria, with resultant decreased oxidative phosphorylation and adenosine triphosphate (ATP) synthesis.

What is the most common cause of hypoxia?

ISCHEMIA (obstruction of arterial blood flow), which is the most common cause

What is released from dead cells?

Intracellular enzymes and various other proteins are released from

What is liquefactive necrosis?

Ischemic injury to the central nervous system (CNS) characteristically results in liquefactive necrosis. After the death of CNS cells, liquefaction is caused by autolysis. Suppurative infections characterized by the formation of pus (liquefied tissue debris and neutrophils) by heterolytic mechanisms involve liquefactive necrosis.

What is an example of hyperplasia?

It is exemplified by glandular proliferation in the breast during pregnancy. In some cases, hyperplasia occurs together with hypertrophy. During pregnancy, uterine enlargement is caused by both hypertrophy and hyperplasia of the smooth muscle cells in the uterus.

When does hypoplasia occur?

It is seen in the partial lack of growth and maturation of gonadal structures in Turner syndrome and Klinefelter syndrome.

How long does irreversible hypoxic injury take in muscle?

Many hours for skeletal muscle cell

When does atrophy work?

Most often, causal factors are disuse, nutritional or oxygen deprivation, diminished endocrine stimulation, aging, and denervation (lack of nerve stimulation in peripheral muscles caused by injury to motor nerves). Characteristic features often include the presence of autophagic granules, which are intracytoplasmic vacuoles containing debris from degraded organelles. In some instances, atrophy is thought to be mediated in part by the ubiquitin- proteasome pathway of protein degradation. In this pathway, ubiquitin-linked proteins are degraded within the proteasome, a large cytoplasmic protein complex.

What does caseous necrosis look like?

On histologic examination, caseous necrosis has an amorphous eosinophilic appearance

How long does hypoxic injury take t become irreversible in the heart?

One to 2 hours for myocardial cells and hepatocytes

Is the cause of dystrophic calcification hypercalcemia?

The cause is not hypercalcemia; typically, the serum calcium concentration is normal

What is the cause of metastatic calcification?

The cause of metastatic calcification is hypercalcemia.

What is fibrinoid necrosis?

This deposition of fibrin-like proteinaceous material in the arterial walls appears smudgy and acidophilic. Fibrinoid necrosis is often associated with immune-mediated vascular damage.

What is hemosiderin?

This iron-containing pigment consists of aggregates of ferritin. It appears in tissues as golden brown amorphous aggregates and can be positively identified by its staining reaction (blue color) with Prussian blue dye. It exists normally in small amounts as physiologic iron stores within tissue macrophages of the bone marrow, liver, and spleen

What is bilirubin?

This pigment is a catabolic product of the heme moiety of hemoglobin and, to a minor extent, myoglobin.

What enzyme forms melanin?

This pigment is formed from tyrosine by the action of tyrosinase, synthesized in melanosomes of melanocytes within the epidermis, and transferred by melanocytes to adjacent clusters of keratinocytes and also to macrophages (melanophores) in the subjacent dermis.

What is gangrenous necrosis?

This type of necrosis most often affects the lower extremities or bowel and is secondary to vascular occlusion.

What is casseous necrosis?

This type of necrosis occurs as part of granulomatous inflammation and is a manifestation of partial immunity caused by the interaction of T lymphocytes (CD4+, CD8+, and CD4−CD8−), macrophages, and probably cytokines, such as interferon-γ, derived from these cells.

What is lipofuscin?

This yellowish, fat-soluble pigment is an end product of membrane lipid peroxidation. It is sometimes referred to as "wear-and-tear" pigment. It commonly accumulates in elderly patients, in whom the pigment is found most often within hepatocytes and at the poles of nuclei of myocardial cells. The combination of lipofuscin accumulation and atrophy of organs is referred to as brown atrophy.

How long does it take for hypoxic injury in the brain, and what neurons are most susceptible?

Three to 5 minutes for neurons. Purkinje cells of the cerebellum and neurons of the hippocampus are more susceptible to hypoxic injury than are other neurons.

What is traumatic fat necrosis?

Traumatic fat necrosis, which occurs after a severe injury to tissue with high fat content, such as the breast

What is dry gangrenen?

When characterized primarily by coagulative necrosis without liquefaction, gangrenous necrosis is called

What is wet gangrene?

When complicated by infective heterolysis and consequent liquefactive necrosis, gangrenous necrosis is called wet gangrene.

Is squamous metaplasia reversible?

YES

What is osseous metaplasia?

a. Osseous metaplasia is the formation of new bone at sites of tissue injury. b. Cartilaginous metaplasia may also occur.

What is fatty change?

accumulation of intracellular parenchymal triglycerides and is observed most frequently in the liver, heart, and kidney. For example, in the liver, fatty change may be secondary to alcoholism, diabetes mellitus, malnutrition, obesity, or poisonings.

What diseases have decreased melanin?

albinism and vitiligo.

What is a TUNEL assay (Terminal Transferase dUTP Nick End Labeling?

are ways to quantitate cleaving of nucleosomes and, thus, apoptosis. Similarly, caspase assays are coming into use as apoptotic markers. Surely more will follow.

What is pyknosis?

chromatin clumping and shrinking with increased basophilia

What is karyolysis?

fading of chromatin material

What is kryorrhexis?

fragmentation of chromatin

What is the intrinsic pathway of apoptosis?

initiated by the loss of stimulation by growth factors and other adverse stimuli, results in the inactivation and loss of bcl-2 and other antiapoptotic proteins from the inner mitochondrial membrane. This loss results in increased mitochondrial permeability, the release of cytochrome c, and the stimulation of proapoptotic proteins such as bax and bak. Cytochrome c interacts with Apaf-1 causing self-cleavage and activation of caspase-9. Downstream caspases are activated by upstream proteases and act themselves to cleave cellular targets.

What are signs of irreversible cell damage?

irreversible damage to cell membranes, leading to massive calcium influx, extensive calcification of the mitochondria, and cell death.

What increases melanin pigmentation?

is associated with sun tanning and with a wide variety of disease conditions.

What is hemosiderosis?

is defined by accumulation of hemosiderin, primarily within tissue macrophages, without associated tissue or organ damage.

What are the three regulators of apoptosis?

is mediated by a number of genes and their products. Important genes include 1) bcl-2 (gene product inhibits apoptosis), 2) bax (gene product facilitates apoptosis), 3) p53 (gene product decreases transcription of bcl-2 and increases transcription of bax, thus facilitating apoptosis).

What is hemochromatosis?

is more extensive accumulation of hemosiderin, often within parenchymal cells, with accompanying tissue damage, scarring, and organ dysfunction. This condition occurs in both hereditary (primary) and secondary forms.

What is metaplasia?

is the replacement of one differentiated tissue by another

What is necrosis?

is the sum of the degradative and inflammatory reactions occurring after tissue death caused by injury (e.g., hypoxia and exposure to toxic chemicals); it occurs within living organisms. In pathologic specimens, fixed cells with well-preserved morphology are dead but not necrotic.

What is plumbism?

lead poisoning

What is the extrinsic pathway of initiation for apoptosis?

mediated by cell surface receptors exemplified by FAS, a member of the tumor necrosis factor receptor family of proteins. This pathway is initiated by the signaling of molecules such as the FAS ligand, which in turn signals a series of events that involve activation of caspases. Caspases are aspartate-specific cysteine proteases that have been referred to as "major executioners" or "molecular guillotines." The death signals are conveyed in a proteolytic cascade, through activation of a chain of caspases and other targets. The initial activating caspases are caspase-8 and caspase-9, and the terminal caspases (executioners) include caspase-3 and caspase-6 (among other proteases).

What are the 3 signs of hereditary hemochromatosis?

micronodular cirrhosis, diabetes mellitus, and skin pigmentation. bronze diabetes increased srum iron and decreased TIBC

What causes hereditary hemochromatosis?

most often caused by a mutation in the Hfe gene on chromosome 6. Over 20 distinct mutations have been identified, the most common of which is the C282Y mutation, followed by the H63D mutation

hat is secondar hemochromatosis?

most often caused by multiple blood transfusions administered to subjects with hereditary hemolytic anemias such as β-thalassemia major.

What are the two morphologic patterns of tissue deah?

necrosis and apoptosis

What is heterolysis?

refers to cellular degradation by enzymes derived from sources extrinsic to the cell (e.g., bacteria and leukocytes).

What is autolysis?

refers to degradative reactions in cells caused by intracellular enzymes indigenous to the cell. Postmortem autolysis occurs after the death of the entire organism and is not necrosis

What are signs of early phosphofructokinase activity in cell hypoxic injury?

results in increased glycolysis, accumulation of lactate, and decreased intracellular pH. Acidification causes reversible clumping of nuclear chromatin.

How is apoptosis activated by cytotoxic T cell activation?

s characterized by direct activation of caspases by granzyme B, a cytotoxic T-cell protease that perhaps directly activates the caspase cascade. The entry of granzyme B into target cells is mediated by perforin, a cytotoxic T-cell protein.

What organ does CCl4 cause damage to?

the liver, P450 system of mixed function oxidases within the SER and produces highly reactive CCl3- CCl3- causes lipid peroxidation of intracellular membranes causing diaggregation of ribosomes and results in decreased protin synthesis, failure to synthesize apoprotein moiety of and FATTY CHANGE Plasma membrane damage caused by lipid peroxidation in the SER, resulting in cell swelling nd calcium influx

What is the role of transglutaminases in apoptosis?

they cross link apoptotic cytoplasmic proteins

What are the two forms of fat necrosis?

traumatic fat necrosis enzymatic fat necrosis

What is the leading cause of caseous necrosis?

tuberculosis

What is anemia?

which is a reduction in the number of oxygen-carrying red blood cells

What are diseases of abnormal protein aggregation?

which is characteristic of amyloidosis; a number of neurodegenerative diseases, such as Alzheimer disease, Huntington disease, and Parkinson

What are disease of transport and secretion?

which is characteristic of cystic fibrosis and α1-antitrypsin deficiency

How does CO poisoning occur?

which results in diminution in the oxygen-carrying capacity of red blood cells by chemical alteration of hemoglobin