Late in the process, the apoptotic cell begins (1) of the surface (numerous surface projections) and then the cell produces several (2) which either contain (3) or both.
1. blebbing 2. membrane-bound apoptotic bodies 3. nuclear fragments, cytoplasmic fragments with organelles
The JGA also has baroreceptors which directly release (1) if the (2) decreases
1. renin 2. blood pressure
Apoptotic bodies are then phagocytosed by (4)
(1) in essential hypertension preferentially affects the (2) arteriole unlike diabetes which affects (3).
1. Hyaline atherosclerosis 2. afferent 3. both the afferent and efferent arterioles
In extremely high blood pressure, the blood vessels can constrict and squeeze the (1), resulting in (2) and a fairly specific appearance of (1) on slides which are known as (3), which occur due to mechanical injury.
1. red blood cells 2. hemolysis 3. schistocytes
As the (1) cells proliferate due to PDGF release, they continue to obstruct the blood vessel lumen which further increases the blood pressure. (2) can then occur from the increased pressure.
1. myointimal 2. Fibrinoid necrosis
Pathologists can generally identify cells which are undergoing apoptosis by their appearance, particularly the so-called (1) which are the final cellular stages of dying apoptotic cells.
1. apoptotic bodies
Intracellularly, the major pathway for apoptosis involves a mechanism for (1) to basically destroy themselves by releasing key proteins which they need for the production of energy. Specifically, they leak out (2), which drastically reduces the cell’s capacity for aerobic metabolism.
1. mitochondria 2. Cytochrome C
Elevated blood pressure can either be primary (1) or secondary to a number of disorders (2).
1. essential hypertension 2. for example renovascular hypertension
Necrotic tissues can show a structural (1) known as (2) for 12-24 hours before the cells are completely digested
1. “ghosting” 2. coagulative necrosis
Growth and survival signals stimulate production of anti-apoptotic proteins such as (1).
1. Bcl-2 and Bcl-x
Atherosclerosis is influenced by Virchows triad which includes (1). As the renal function decreases, the blood pressure increases due to increases in (2) and sodium reabsorption, leading to further renal damage.
1. endothelial damage, changes in blood flow, and differences in blood coagulation 2. angiotensin II
The kidney has complex autoregulatory mechanisms which try to protect it from variations in renal blood flow due to circulatory changes. Unfortunately, this autoregulation doesn’t function effectively at blood pressures above about (1) mm Hg, so the increased blood pressure becomes transmitted directly to the renal vessels and glomeruli
nuclear shrinkage (EM changes in necrosis)
nuclear degradation (EM changes in necrosis)
Apoptotic cells cleave DNA in a specific pattern due to the presence of (1), so when the DNA is electrophoresed, it shows a regular pattern on a gel known as a (2) due to the specific spacing of (3).
1. chromatin conformations 2. “DNA ladder” 3. nucleosomes
As cells undergo apoptosis, they (1). This process is called (2), and is a key morphologic feature of apoptosis.
1. shrink, their cytoplasm becomes more dense, and the chromatin (nuclear material) aggregates at the periphery of the nuclear membrane 2. chromatin condensation
Alternatively, cellular stress or injury leads to production of pro-apoptotic signals such as (1) that activate (2) which are pro-apoptotic proteins, which insert into the (3) creating channels thru which mitochondrial inner membrane proteins such as cytochromes leak out of the mitochondria and into the cytoplasm.
1. Bid and Bad 2. Bax and Bak 3. mitochondrial membrane
Complications of malignant hypertension include damage to the (1).
1. eyes, brain, kidney, and red blood cells
The (1) pathway can be employed to apoptose groups of cells, so it is a highly regulated mechanism
In addition to DNA laddering, apoptosis can be detected by specialized assays such as (1) or identification of other apoptotic proteins or properties.
1. caspase-3 activity or endonuclease activity
Necrotic tissues are generally “pinker” than normal cells because of the loss of (1) which stains blue with the hematoxylin
1. cytoplasmic RNA
Fas ligand is expressed on (1) cells and binds to Fas producing activation of (2).
1. T 2. FADD (Fas-associated death domain)
Several other caspases, including (1) serve as executioner proteases which cleave proteins that lead to dissolution of cell membranes, nucleic acids, and organelles
1. caspase-3 and caspase-6,
In contrast, necrotic cell death usually forms a (1) if the DNA is degraded due to the more random destruction of nucleic acids by this process.
Malignant hypertension is due to these extremely high pressures which directly produce vascular damage leading to (1) damage and cell death by necrosis or apoptosis.
1. endothelial and medial
When necrosis is due to (2), the most common pattern is called (1): a pattern where the structure is maintained although the nuclei and cell borders increasingly disappear.
2. ischemia from poor blood flow 1. coagulative necrosis
Necrosis can lead to a number of ultrastructural (electron microscopic) findings such as : 1); 2); 3); 4); and 5)
1. hydropic change: vacuolated cytoplasm 2. myelin figures: phospholipid masses 3. karyolysis: nuclear degradation 4. pyknosis: nuclear shrinkage 5. karyorrhexis: nuclear fragmentation
Because cells are very complicated, there is also an inhibitor of apoptosis within cells known as (1), which can bind to (2) and block its cleavage.
1. FLIP 2. pro-caspase-8
There is both an intrinsic apoptosis pathway in which (1) may apoptosis and an extrinsic pathway in which (2) apoptosis because of either a response to a pro-apoptotic factor or the loss of survival factors such as growth factors.
1. individual cells 2. entire groups of cells
Apoptosis initiates with (1), and is completed by executioner caspases such as (2).
1. caspases-8 and 9 2. 3 and 6
The (1) senses reduced sodium concentration in the (2) and interprets this as reduced (3). There is then a corresponding dilation of the (4) arteriole in that nephron, and a release of (5) which induce nearby (6) cells to release (7).
1. macula densa 2. distal tubule 3. blood flow 4. afferent 5. prostaglandins 6. juxtaglomerular apparatus (JGA) 7. renin
Elevated blood pressure is associated with a (1) with (2) material within blood vessels which leads to obstruction of the lumen and increasing blood pressure as well as decreased blood flow. The kidney is highly susceptible to damage by high blood pressure because it is such a vascular organ.
1. hyaline arteriolosclerosis 2. eosinophilic
FADD then activates (3), which initiates the extrinsic autocatalytic cleavage process of caspases which interacts with the intrinsic pathway as well.
If the blood vessel restores blood flow after irreversible damage has occurred, then there can be some injury from this renewed blood pressure damaging the structurally damaged tissues. This is known as (1).
1. reperfusion injury
DNA ladder on electrophoresis
High blood pressure has serious chronic effects on the body and creates markedly increased risk for (1) disease.
1. renal and heart
(1) can occur within the fundus and hemorrhages can occur in the brain (particularly in the area of the (2).
1. Papilledema, hemorrhages, and exudates 2. basal ganglia and internal capsule
Hypertensive urgency is a systolic blood pressure of greater than (1) mm Hg or a diastolic blood pressure of greater than (2) mm Hg with no evidence of end organ damage. Hypertensive emergency is defined as BP above either of these levels plus (3)
1. 220 2. 120 3. end organ damage to eye, blood, kidney, heart, or brain.
After injury, apoptosis eliminates cells which are irreversibly damaged in certain settings. The advantage of this over the alternative death pattern (necrosis), is that it is controlled and does not introduce (1) from injured cells to the (2).
1. antigens 2. immune system (thereby eliciting undesired continued inflammation or autoimmune conditions)
During apoptosis, the (1) moves to the outer membrane which is the basis for binding by a protein named (2), which can also be used as a stain for apoptosis.
1. phospholipid phosphatidylserine 2. annexin V
Many believe that ischemia itself reduces enzymatic activity so proteolysis is inhibited and the (2) cells may persist for days or weeks.
2. pink anucleate
(1) presents histologically as (2) material found in the vessel wall replacing the viable cells which are now dead
1. Fibrinoid necrosis 2. pinkish fibrin-like
phospholipid masses (EM changes in necrosis)
Morphologically, necrotic cells do not show intermediate forms like apoptotic bodies but appear to be destroyed by their own (1) with loss of (2) and essentially a slow cell lysis.
1. lysosomal enzymes 2. membranes
DNA smear on electrophoresis
The specific overarching mechanism which regulates apoptosis is the use of (1), which are proteases which cleave proteins at specific residues, usually after (2) residues.
1. caspases 2. aspartic acid
Cytochrome C then binds to a protein called (1), which binds and activates (2) beginning the caspase cleavage process.
1. Apaf-1 2. caspase-9
(1) from necrotic cells leak into surrounding tissues and the blood which can be used to identify necrosis diagnostically.
1. Cell proteins and membranes
(1) ligand interact with the (2) receptor and the (3) receptor respectively, and are important extrinsic signals for induction of cell death.
1. TNF and Fas 2. TNF 3. Fas/FADD
The (1) damage from very high arterial blood pressures leads to (2) at sites where the (1) cell membrane is disrupted and (3) is exposed.
1. endothelial 2. platelet deposition 3. vonWillebrand factor (vWF)
Most pathology tissues are stained with hematoxylin which stains (1); and eosin which stains (2)
1. nucleic acids blue 2. proteins and carbohydrates pink
Release of the cytochromes and other mitochondrial proteins is controlled by a balance between the pro-and anti apoptotic members of the (1) family of proteins (there are more than 20 of these but we will only talk about the main ones).
(1) enzymes and other enzymes from (2) also contribute to the elimination of necrotic cellular material.
1. Lysosomal 2. neutrophils
nuclear fragmentation (EM changes in necrosis)
vWF exposure leads to release of (1) which leads to proliferation of the (2) cells.
1. platelet derived growth factor (PDGF) 2. myointimal
Apoptosis is controlled by the expression of a series of specific apoptosis genes which are highly conserved back to (1), where they were initially described.
Coagulative necrosis is also called (1) and a focal area is called (2). These are often wedge-shaped because the blood flow for many organs enters from the center or hilum of the organ.
1. infarction 2. an infarct
Initiator caspases include (1)
1. caspase-8 and caspase-9.
Some of the risk factors for primary hypertension include (1).
1. cigarette smoking, obesity, alcohol abuse, high sodium diet, low potassium diet, stress, family history, and age
One interesting aspect of this regulated process is that most caspases are created as (1), but contain internal sequences which allow them to be cleaved. Thus activated by other caspases, there can be a cascade of different caspases in the pathway.
1. inactive pro-enzymes