Usmle part 1
part 15
DANIL HAMMOUDI.MD
DIHYDROXYACETONE PHOSPHATE IS THE INTERMEDIATE PRODUCTS OF GLYCOLYSIS FOR FAT STORAGE.
Storage in the adipose tissue is catalysed by lipoprotein lipase, the activity of which is stimulated by insulin(the same hormone which stimulates storage of glucose as glycogen).
ß-oxidation of fatty acids
This is a cyclic series of reactions (occurring within the mitochondria) with the end result of two carbon units being hydrolysed from the fatty acid chain with each cycle. These two carbon units are molecules of acetyl CoA.
With each oxidation cycle, a molecule of NAD is reduced to NADH and one FAD is reduced to FADH. These are re-oxidised by the electron transport chainwith the energy released coupled to ATP synthesis.
The acetyl CoA molecules formed in each cycle are oxidised to CO2in the citric acid cycle, with the oxidation/reduction reactions coupled to the electron transport chain and further ATP synthesis.
These events occur in liver and muscle. During sustained exercise the cells of slow twitch muscle fibres (which possess mitochondria) utilise ß-oxidation as the major source of ATP.
Ketone bodies
An alternative method of utilising the acetyl CoA formed by ß-oxidation is via the synthesis and subsequent oxidation of four-carbon units known collectively as ketone bodies.
Acetyl CoA is converted in the liver into acetoacetate (essentially two acetyl groups covalently linked). Acetoacetate can be further reduced to form ß-hydroxybutyrate. These two compounds are referred to as ketone bodies. Their synthesis occurs in the liver.
They diffuse from the liver into the circulation and are used as fuels by several tissues. Heart muscle and renal cortex, in particular, use acetoacetate in preference to glucose. In contrast, glucose is the major fuel for the brain and erythrocytes in a human on a balanced diet. The brain has the capacity to adapt to the use of acetoacetate during starvation (and in the metabolic disease diabetes mellitus). In starvation of long standing, acetoacetate meets more than 70% of the energy needs of the brain.
This ability of the brain to adapt to the use of acetoacetate is important because fatty acids cannot enter neural tissue. Acetoacetate is regarded as a water soluble and readily transported form of acetyl CoA.
The efficiency (amount of ATP produced) of oxidation of fatty acids directly or via formation of ketone bodies is approximately the same - there is no penalty to the body in converting acetyl CoA to this water soluble form.
It is important to be aware thatthere is no mechanism in animals for the conversion of fatty acids to glucose.
Fatty acid synthesis
This occurs in the cytoplasm of cells (compared to ß-oxidation which occurs inside the mitochondria).
The process begins with acetyl CoA and cyclic reactions join two-carbon units to the growing fatty acid chain. The completion of the synthesis and the formation of unsaturated fatty acids is complex.
The role of fatty acid synthesis is to :
supply the body's needs for particular fatty acids not supplied in the diet AND
to convert excess dietary glucose to fatty acids for storage
Glucose is converted to pyruvate (glycolysis), then to acetyl CoA which, when ATP is required, is oxidised by the citric acid cycle. If the glucose intake exceeds the body's energy needs (and after saturation of glycogen stores) the acetyl CoA can be used for fatty acid synthesis (in the liver) and storage as triglyceride in adipose tissue.
A newborn presents with severe
acidosis, vomiting, hypotonia, and neurologic deficits. Serum analysis reveals
elevated levels of lactate and alanine. These observations suggest a deficiency
in which of the following enzymes?
A. Alanine aminotransferase
B. Glutamate dehydrogenase
C. Lactate dehydrogenase
D. Pyruvate carboxylase
E. Pyruvate dehydrogenase
A group of patients with lung
cancer is matched to a group of patients without lung cancer. Their smoking
habits over the course of their lives is compared.
Based on this information, researchers compute the rate of lung cancer in
patients who smoke versus those who never smoked. This is an example of
A. case-control
study
B. cohort study
C. cross-sectional study
D. longitudinal study
E. randomized control study
A pharmacologist is examining a
new drug with potential sedative properties. He begins by analyzing the
pharmacokinetic properties of the drug. Studies of the drug's rate of
elimination yield the above data. Which of the following drugs has similar
kinetics to the drug being studied?
A. Carbamazepine
B. Cimetidine
C. Ethanol
D.
Ketoconazole
E.
Phenobarbital
A 46-year-old woman presents to
her doctor complaining of weakness and fatigue. On physical examination, her
physician notices a 10-pound weight gain since her last visit 6 months ago. Her
blood pressure is 160/100 mmHg. Blood tests reveal serum Na+ 155 mEq/L, K+ 2.8
mEq/L, and a decreased serum renin. Which of the following is the most likely
diagnosis?
A. Cushing's
syndrome
B. Diabetes
mellitus
C.
Pheochromocytoma
D. Primary
aldosteronism
E. Secondary
aldosteronism
A 38-year-old woman complains
of cold, painful fingertips, as well as difficulty swallowing and indigestion.
Physical examination is remarkable for a thickened, shiny epidermis over the
entire body, with restriction of movement of the extremities, particularly the
fingers, which appear claw-like. Which of the following autoantibodies is likely
to be found in this patient's serum?
A. Anti-DNA topoisomerase I (anti-Scl-70)
B.
Anti-double-stranded DNA (ds DNA)
C. Anti-IgG
D. Anti-Sm
E.
Anti-SS-A
A 26-year-old woman and her
29-year-old husband have been trying to have a child for the last 3 years.
During this time the woman has had 5 spontaneous abortions. The karyotypes of
the mother, father, and the most recently aborted fetus all contained 46
chromosomes, and all pairs were normal except for the pairs shown below.
The
event that led to the child's abnormal karyotype was:
A.
adjacent I segregation
B.
adjacent II segregation
C.
alternate segregation
D. a
recombination event within a paracentric inversion
E. a recombination event within a pericentric
inversion
A 70-year-old woman undergoes a
gastrectomy for Zollinger-Ellison syndrome. Her doctor informs her that she will
need to take intramuscular vitamin B12 shots for the rest of her life. Absence
of which of the following cell types is responsible for
this vitamin replacement requirement?
A. Chief cells
B. G cells
C. Goblet cells
D. Mucous neck cells
E. Parietal cells
A patient presents with right
lower quadrant pain, fever, and diarrhea. Physical examination reveals diffuse
abdominal tenderness; laboratory examination reveals a moderate leukocytosis,
leading to a presumptive diagnosis of acute appendicitis. Surgical exploration
of the abdomen reveals mesenteric adenitis, but the appendix is normal. Which of
the following organisms is most likely responsible for these signs and
symptoms?
A. Clostridium
difficile
B.
Enterohemorrhagic E. coli
C. Enteroinvasive E. coli
D. Enteropathogenic E. coli
E. Yersinia enterocolitica
Mean
arterial blood pressure (MAP) and heart rate (HR) measurements were recorded
during the intravenous administration of two different drugs. Select the most
likely drugs given at the indicated points.
A. X, Acetylcholine Y,phentolamine
B. X, epinephrine Y,hexamethonium
C. X, isoproterenol Y, propranolol
D. X, metaproterenol Y,
propranolol
E. X, norepinephrine
Y, hexamethonium
A 21-year-old man is competing
in a weight-lifting competition. He lifts 325 lbs over his head and holds it
there for 5 seconds. Suddenly, his arms give way and he drops the weights to the
floor. Which of the following receptors is responsible for this sudden muscle
relaxation?
A. Free nerve
ending
B. Golgi tendon
organ
C. Merkel's disk
D. Muscle spindle
A normal volunteer consents to
an intravenous infusion of p-aminohippuric acid (PAH). After a short time, the
plasma PAH is 0.02 mg/ml, the concentration of PAH in urine is 13 mg/ml and the
urine flow is 1.0 ml/min. What is the effective renal plasma flow?
A. 0.26 ml/min
B. 26 ml/min
C. 65 ml/min
D. 260 ml/min
E. 650 ml/min
A 4-day-old male is brought to
the pediatric clinic because of breathing difficulties and poor feeding. He
coughs, chokes, and spits up milk very soon after beginning to suckle. Physical
exam and radiographs reveal the presence of the most common type of
tracheoesophageal fistula. The baby's defect likely resulted from:
A.
failure of the buccopharyngeal membrane to rupture
B. failure of the tracheoesophageal ridges to fuse
C. incomplete formation of the septum
secundum
D. incomplete
recanalization of the larynx
E.
patent thyroglossal duct
A 4-month-old blue-eyed,
fair-skinned child who appeared normal at birth is brought to the pediatrician
because of the development of scaly skin lesions and seizures. On physical
examination, the infant appears to be mentally retarded, and a musty odor is
noted. Which of the following defects is responsible for this child's
illness?
A. Deficiency of
alpha-ketoacid decarboxylase
B.
Deficiency of hexosaminidase A
C. Deficiency of homogentisate oxidase
D. Deficiency of hypoxanthine-guanine
phosphoribosyltransferase
E.
Deficiency of phenylalanine hydroxylase
A 31-year-old stockbroker
drives to a high-altitude mountain resort to do some rock-climbing. Later that
day, he experiences headache, fatigue, dizziness, and nausea. Which point on the
graph above best corresponds to the relationship between plasma bicarbonate, pH,
and PCO2 in this patient?
A.
Point A
B. Point B
C. Point C
D. Point D
E.
Point E
A 13-year-old male presents to
the emergency room with a deep skin abrasion on his knee. He states that it has
not stopped bleeding since it happened during recess approximately 20-30 minutes
ago. Physical examination reveals a well-developed, well-nourished adolescent.
There are multiple purpura over his legs and arms, and
a few scattered petechiae on his chest and gums. His bleeding time is 22
minutes, platelets = 300,000/mm3, hemoglobin = 11g/dL. A trial of
cryoprecipitate transfusion does not improve his bleeding time. A normal
platelet transfusion does improve bleeding time. Which of the following is the
correct diagnosis?
A.
Bernard-Soulier syndrome
B.
Henoch-Schönlein purpura
C.
Idiopathic thrombocytopenic purpura
D. Thrombotic thrombocytopenic purpura
E. Von Willebrand's disease
An 88-year-old male complaining
of abdominal pain enters the emergency room with his wife. A mini-mental status
exam reveals pronounced forgetfulness and confusion. The patient is discovered
to have acute appendicitis requiring immediate surgery. He is unable to
understand the situation and cannot provide informed consent. Which of the
following further actions must the physician take?
A. Do not perform surgery
B. Have another doctor confirm the necessity of
surgery
C. Obtain a court order
to perform surgery
D. Obtain
consent from his wife to perform surgery
E. Try to persuade the patient to consent to
surgery
A 42-year-old obese woman
experiences episodic abdominal pain. She notes that the pain increases after the
ingestion of a fatty meal. The action of which of the following hormones is
responsible for the postprandial intensification of her symptoms?
A. Cholecystokinin
B. Gastrin
C. Pepsin
D.
Secretin
E.
Somatostatin
Which of the pharyngeal pouches
develops into the palatine tonsil?
A. First
B.
Second
C. Third
D. Fourth
E. Fifth
A worried mother complains to
her pediatrician that both she and her 6-year-old son's teacher have noticed
that the child has become inattentive. She states that her son frequently stops
what he is doing and "stares blankly into space" before resuming his activities.
Electroencephalography reveals a 3/second spike and slow wave pattern of
discharges. Which of the following agents would most effectively treat this
child's disorder?
A.
Carbamazepine
B.
Diazepam
C.
Ethosuximide
D.
Methylphenidate
E.
Phenytoin
In the family shown above,
individuals affected with profound deafness are represented by a shaded symbol.
The phenotypes of individuals in the fourth generation can best be explained by:
A. autosomal dominant
inheritance
B. locus
heterogeneity
C. mitochondrial
inheritance
D. multifactorial
inheritance
E. X-linked dominant
inheritance
At which point on the diagram
above would the length of the myocardial sarcomere be approximately 2 mm with
maximal actin-myosin cross bridging?
A. A
B.
B
C. C
D. D
E. E
Absence of which of the
following enzymes would impair the rate-limiting step of
glycogenolysis?
A.
alpha-1,4-glucan transferase
B. Glycogen phosphorylase
C. Glycogen synthase
D. Phosphoglucomutase
E. UDP-glucose pyrophosphorylase
A 34-year-old female is brought
to her family physician by her brother. He states that the patient's husband had
run away with another woman the previous day. After discovering this, the
patient arrived at her brother's home in a "dazed state," was unable to function
appropriately the remainder of the evening, and slept fitfully all night. Early
in the morning she began to talk to people who were not present, and debated
whether or not to kill her children and herself. He denies anything like this
ever happening before. Which of the following is the most likely
diagnosis?
A. Bipolar
disorder
B. Brief psychotic
disorder
C. Schizoaffective
disorder
D. Schizophrenic
disorder
E. Schizophreniform
disorder
A 34-year-old woman presents
with abdominal pain and reports changes in her bowel habits. On pelvic
examination a mass is palpated on her right ovary. Laparoscopic surgery is
performed and the mass is removed. The gross appearance of the tumor is shown
below. What type of tumor is it?
A. Choriocarcinoma
B. Dysgerminoma
C. Fibroma
D.
Granulosa-theca cell
E.
Teratoma
A 55-year-old woman is
receiving chemotherapy for non-Hodgkin's lymphoma. Several days after a
treatment, she notes that she has blood in her urine. Which of the following
antineoplastic drugs is most likely responsible for this side
effect?
A.
Bleomycin
B. Cisplatin
C. Cyclophosphamide
D. Doxorubicin
ANSWERS
Question 1:
BIO GP
A newborn presents
with severe acidosis, vomiting, hypotonia, and neurologic deficits. Serum
analysis reveals elevated levels of lactate and alanine. These observations
suggest a deficiency in which of the following enzymes?
A.
Alanine aminotransferase
B. Glutamate dehydrogenase
C.
Lactate dehydrogenase
D. Pyruvate carboxylase
E. Pyruvate
dehydrogenase
The correct
answer is: E.
Description: |
Question
2: BESCI GP
A group of
patients with lung cancer is matched to a group of patients without lung
cancer. Their smoking habits over the course of their lives is compared. Based on
this information, researchers compute the rate of lung cancer in patients who
smoke versus those who never smoked. This is an example of
A. case-control study
B. cohort
study
C. cross-sectional study
D. longitudinal
study
E. randomized control study
The correct answer is:
A.
Description: |
Question 3:
PHARM GP
A
pharmacologist is examining a new drug with potential sedative properties. He
begins by analyzing the pharmacokinetic properties of the drug. Studies of the
drug's rate of elimination yield the above data. Which of the following drugs
has similar kinetics to the drug being studied?
A.
Carbamazepine
B. Cimetidine
C. Ethanol
D.
Ketoconazole
E. Phenobarbital
. The correct answer is:
C.
Description: |
Question 4:
PATH ENDO
A 46-year-old
woman presents to her doctor complaining of weakness and fatigue. On physical
examination, her physician notices a 10-pound weight gain since her last visit 6
months ago. Her blood pressure is 160/100 mmHg. Blood tests reveal serum Na+ 155
mEq/L, K+ 2.8 mEq/L, and a decreased serum renin. Which of the following is the
most likely diagnosis?
A. Cushing's syndrome
B.
Diabetes mellitus
C. Pheochromocytoma
D. Primary
aldosteronism
E. Secondary aldosteronism
Correct, you answered
D.
Description: |
Question 5:
IMMU GP
A 38-year-old woman complains of cold, painful fingertips, as
well as difficulty swallowing and indigestion. Physical examination is
remarkable for a thickened, shiny epidermis over the entire body, with
restriction of movement of the extremities, particularly the fingers, which
appear claw-like. Which of the following autoantibodies is likely to be found in
this patient's serum?
A. Anti-DNA topoisomerase I
(anti-Scl-70)
B. Anti-double-stranded DNA (ds
DNA)
C. Anti-IgG
D. Anti-Sm
E.
Anti-SS-A
The correct answer is:
A.
Description:
|
Question 6:
BIO GP
A 26-year-old woman
and her 29-year-old husband have been trying to have a child for the last 3
years. During this time the woman has had 5 spontaneous abortions. The
karyotypes of the mother, father, and the most recently aborted fetus all
contained 46 chromosomes, and all pairs were normal except for the pairs shown
below.
The
event that led to the child's abnormal karyotype was:
A. adjacent
I segregation
B. adjacent II segregation
C. alternate
segregation
D. a recombination event within a paracentric
inversion
E. a recombination event within a pericentric
inversion
You answered D. The correct answer is:
B.
Description: |
Segregation from a quadrivalent ring results in three
different patterns of 2 x 2
segregation.
Translocations in man:
1.
Down’s syndrome is caused by trisomy #21, and usually stems
from primary or secondary non-disjunction. Thus,
2n = 46N vs 2n = 47D
2.
About 5% of Down’s individuals are 2n = 46D, and all 2n = 46D
individuals have one parent that is 2n = 45N, i.e.,
2n = 46N vs
2n = 46D vs 2n = 45N
3.
Chromosome studies indicated involvement of chromosomes #15
and #21, and based on observations of “standard” (normal) karyotypes, a
non-reciprocal translocation between chromosomes #15 and #21 was hypothesized to
be responsible for the 2N = 46D individuals.
a)
One product of the translocation (the 15/21 chromosome)
contained most or all of the euchromatin of both chromosomes; whereas the
reciprocal product (the 21/15 chromosome) contained mostly heterochromatin and a
chromosomal NOR. Loss of the 21/15 chromosome thus was not expected to
have phenotypic consequence.
b)
Matings between a 2n = 45N (translocation heterozygote) and a
2n = 46N normal individual would thus yield…
2/3
aneuploid gametes: zygotic lethality except for the 2n =
46D
1/3
euploid gametes: normal zygotes, one of which is a translocation
heterozygote
i)
Note that the tendency to have Down’s children can be inherited.
ii)
Note also that translocations between D group (#13-#15)
and G group (#21, #22) chromosomes in humans occur much more frequently than
translocations between all other chromosomes in the human
complement.
(a) Because both D and G group
chromosomes in the human complement carry NORs, exchanges may arise between
“homologous regions” of “non-homologous” chromosomes, and may represent a
“price” for the existence of multiple NOR-bearing
chromosomes.
Question 7:
ANAT GI
A 70-year-old woman
undergoes a gastrectomy for Zollinger-Ellison syndrome. Her doctor informs her
that she will need to take intramuscular vitamin B12 shots for the rest of her
life. Absence of which of the following cell types is
responsible for this vitamin replacement requirement?
A. Chief
cells
B. G cells
C. Goblet cells
D. Mucous neck
cells
E. Parietal cells
Correct, you answered
E.
Description: Cholecystokinine =I cell of duodenum and
jejunum Secretin = s cell
duodenum Somatostatin = d cells in pancreatic islets, gi
mucosa |
Introduction
to Glandular Tissue
Glands are organized arrangements of secretory cells. All exocrine glands (and also most endocrine glands), are composed of epithelial tissue.
Although most glands give the appearance of being "solid" tissue, their epithelial nature is expressed by the organization of their cells, with each cell attached laterally to its neighbors. Every exocrine secretory cell has some portion of its plasma membrane exposed to an external surface, communicating with the outside of the body by a system of ducts.
In most glands, the secretory cells are organized into secretory units, which are described according to their shape as tubules, acini, or cords.
Click here to see an example of a very simple gland, from frog skin.
BASIC TERMINOLOGY
Histologically, glands are described using some standard vocabulary, with which you should be familiar.
Simple / Compound
The simple / compound distinction is based on on duct shape.
A simple gland has an unbranched duct (or no duct at all). There is only a single secretory unit (acinus or tubule). Examples include sweat glands, gastric glands, intestinal crypts, and uterine glands.
A compound gland has a branching duct. Salivary glands and pancreas are familiar examples. Compound glands are typically fairly bulky and contain very many individual secretory units (acini or tubules).
Random tissue sections seldom show ducts branching. Nevertheless, the appearance of multiple duct profiles, in various sizes, provides evidence of a branching duct system.
Each secretory unit of a gland consists of cells arranged into an acinus, a tubule, or a cord. Each of of these arrangements has a different and characteristic appearance when viewed in section.
An acinus (from Latin, grape) is a small ball of secretory epithelial cells containing a tiny central lumen. Acini are usually formed by serous cells. [Acini are sometimes called alveoli, from L., small cavity.]
A typical acinar cell is shaped like a pyramid. Its basal surface, located at periphery of the acinus, rests on the basement membrane separating the acinus from the underlying stroma. Its lateral surfaces (the sides of the pyramid) are attached to adjacent secretory cells. Its apical surface is free and faces the acinar lumen, which communicates by duct with the outside. The acinar cell's cytoplasm is also visibly polarized, usually with basophilic basal cytoplasm and variously-staining secretory granules concentrated in apical cytoplasm. For more, see serous cells.
A compound acinar gland can be quite accurately modelled as a bunch of grapes embedded in Jello™. The grapes are the acini, the branching stems are the ducts, and the Jello™ represents the rest of the stroma. Major and minor branches of the bunch represent lobes and lobules, respectively, separated by greater amounts of connective tissue.
In routine tissue sections, most acini are cut in random planes and look like solid lumps, made of cells having various sizes and shapes. The lumen of an acinus is typically tiny (i.e., much smaller than a cell) and so is visible only when an acinus is sliced neatly across the middle. In such a slice, the cells look like slices of pie, with the lumen in the center.
Secretory cells may also arrange themselves into secretory tubules (in contrast to the small balls of cells which comprise secretory acini). Sweat glands are probably the most familiar tubular glands. Other tubular glands include gastric glands (in the lining of the stomach), uterine glands, and various mucous glands of the GI system.
Because tubules are elongated, random sections commonly include the lumen as well as the secretory cells themselves (in contrast to the situation with acini). But interpretation of the sectioned appearance of tubular glands will depend on whether the tubules are simple or branched, on whether they are straight or twisted, and on whether or not adjacent tubules lie parallel to one another.
Cords are arrangements of cells attached to one another to form sheets. In section, the predominant pattern appears linear, even though the lines may twist and branch.
Cords are a common arrangement for epithelial cells that are specialized for endocrine secretion. The cells retain an epithelial character, attached to neighboring cells, even though they may no longer comprise a surface barrier between interstitial space and a secretory lumen that leads to the outside. Examples of endocrine cells arranged into cords include the epithelial cells of pancreatic islets, parathyroid, adrenal cortex, and liver.
The liver (in the thumbnail above) is notable for having cells arranged into cords in spite of its major exocrine function. In order to maintain communication with ducts, the liver cords contain a network of intercellular channels called bile canaliculi.
Endocrine / Exocrine
The suffix -crine refers to secretion; the prefix endo- or exo- tells where the secretory product goes.
The product of exocrine glands leaves the body proper, either by direct secretion onto the body's surface (e.g., sweat) or into the lumen of an organ (e.g., gastric juice) or else by flowing through a system of ducts (e.g., saliva, pancreatic enzymes, bile). The cells of exocrine glands are generally arranged into secretory units in the form of acini or tubules (although the liver has a remarkable arrangement of cords).
The product of endocrine glands is secreted into interstitial fluid and hence into capillaries and general circulation. The cells of endocrine glands are often arranged into cords adjacent to capillaries or sinusoids.
Serous / Mucous / Mixed
The serous / mucous distinction is based on the secretory cell's product -- whether it is a clear, watery solution of enzymes (serous, like serum) or else a glycoprotein mixture (mucous, like mucin). These two categories of secretory products come from two distinct categories of cells, each with a characteristic appearance.
Mixed glands (e.g., most salivary glands) contain both types of cells. Glands which contain only one of these two cell types may be described either as serous glands (e.g., parotid gland or pancreas) or as mucous glands (e.g., Brunner's glands).
Serous cells are specialized to secrete an enzyme solution. Examples include serous cells of the salivary glands, exocrine cells of the pancreas, gastric chief cells, and Paneth cells of intestinal crypts. Serous cells of the pancreas and the salivary glands are typically organized into secretory units called acini.
In routine light microscopy, serous cells are distinguished by basophilic basal cytoplasm, a centrally-located nucleus, and variously-staining secretory vesicles (zymogen granules) in apical cytoplasm. These features are all associated with organized mass production of protein for export. More.
Cells which are specialized to secrete mucus are called mucous cells. Examples include secretory cells of the salivary glands, esophageal glands, stomach surface, pyloric glands, and Brunner's glands of the duodenum. These cells are typically organized into tubular secretory units.
Goblet cells are mucous cells which stand alone within the intestinal epithelium. Goblet cells take their name from their characteristic shape, with a broad opening at the apical end and a narrow, "pinched" base. Cells with this goblet shape are also characteristic of the respiratory tract and the female reproductive tract.
In routine light microscopy, mucous cells are most conspicuously distinguished by "empty"-appearing (i.e., poorly stained) apical cytoplasm and by densely-stained, basal nuclei. More.
Ducts
Ducts are relatively simple tubular structures which are (usually) easily distinguished from blood vessels by their conspicuous cuboidal to columnar epithelial lining. Blood vessels, in contrast, are lined by simple squamous endothelium.
The glandular cells which comprise ducts generally receive much less attention than those which actually secrete the gland's product. However, the complete understanding of a gland requires some awareness of and attention to the duct system through which it drains. Ducts are not just passive "plumbing". Some duct segments actively modify the secretory product passing through, concentrating it by removing water).
For the purpose of describing duct structure and function, especially in compound glands which include branching ducts of various sizes and appearances, some special terminology can be useful. (By and large, the distinctions that these terms allow represent minor details rather than essential knowledge.)
Intercalated / Striated
Intercalated ducts are small ducts which drain individual secretory units. These are usually inconspicuous, lined by a simple epithelium consisting of low cuboidal cells.
In some glands, intercalated ducts lead to striated ducts lined by a simple epithelium consisting of conspicuous cuboidal to columnar cells. In the basal cytoplasm of these cells, fine striations are visible at high magnification.
The cells of the striated ducts are specialized for concentrating the secretory product that is flowing duct. They do this by pumping water and ions across the duct epithelium, from the duct lumen and into interstitial fluid. This striated duct function is carried to extremes in the proximal and distal tubules of the kidney.
Ultrastructurally, striated duct cells display extensive infoldings of the basal membrane. These folds are closely associated with mitochondria that provide ATP for the membrane pumps. In light microscopy, the basal folds and mitochondria are sometimes visible as basal striations, hence the name striated duct.
Secretory / Excretory
Both intercalated and striated ducts are sometimes called secretory ducts. They are located within lobules (intralobular). More distal ducts (interlobular), sometimes called excretory ducts, are generally passive conducting tubes. Their size varies, depending on how many branches have converged proximally. Larger excretory ducts may be lined by stratified cuboidal epithelium.
It is sometimes convenient to refer to ducts by location within the gland. The following terms are all directly descriptive. Intra- means within. Inter- means between. Lobes and lobules are clusters of secretory units served, respectively, by major and minor branches of the duct tree. Within a lobule, individual secretory units are separated from one another by little more than basement membranes and capillaries. In contrast, the stroma which separates lobules and lobes consists of thicker septa of connective tissue. (The distinction between lobes and lobules is arbitrary; lobes are evident upon gross inspection while lobules are evident to low power microscopy.)
Intralobular -- Located within lobules, with no more connective tissue intervening between ducts and secretory units (i.e., acini or tubules) than between adjacent secretory units. Intercalated and striated ducts are intralobular.
Interlobular -- Located between lobules, within the thin connective tissue septa that separate lobules. All interlobular ducts are excretory.
Interlobar -- Located between lobes, within conspicuous, thick connective tissue septa that separate lobes. All interlobar ducts are excretory.
Parenchyma / Stroma
The parenchyma of an organ consists of those cells which carry out the specific function of the organ and which usually comprise the bulk of the organ. Stroma is everything else -- connective tissue, blood vessels, nerves, and ducts.
In most glands, the parenchyma consists of secretory epithelial cells. However, the parenchyma / stroma distinction can be convenient for describing not only glands but also other organs and even tumors. Examples:
· Cardiac muscle cells comprise the parenchyma of the heart. Everything else is stroma.
· Nephrons comprise the parenchyma of the kidney. Everything else is stroma.
· Hepatocytes comprise the parenchyma of the liver. Everything else is stroma.
· Neurons comprise the parenchyma of the brain. Everything else is stroma.
· Cancer cells comprise the parenchyma of malignant neoplasms. Everything else is stroma.
Because parenchyma often seems more interesting, stroma is commonly ignored as just boring background tissue. But no organ can function without the mechanical and nutritional support provided by the stroma. In any gland, connective tissue and capillaries of the stroma envelope every acinus, tubule, or cord, although they are often inconspicuous.
Pay attention to the stroma. If an organ is inflamed, the signs of inflammation appear first in the stroma.
Specialized Cells of the GI System
The GI system includes a number of highly specialized cell types, each differentiated to perform a specific function.
Most of the listed cells are epithelial, since variously specialized epithelia carry out most of the functions which are specific to the GI system. Other tissues are also vitally important to GI function, but are basically similar in all organ systems and are not individually listed here. See separate pages for smooth muscle, for cells of connective tissue (including immune system), and for nerve cells.
Listing of Cells by Region
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| ||||||||||||||||
|
|
Listing of Cells by Function
|
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Listing of Cells by Name
Intestinal Absorptive Cells
Absorptive cells, or enterocytes, are the predominant cell type in the epithelium of the small intestine and colon. These cells are specialized for absorption of nutrients across the apical plasma membrane and export of these same nutrients across the basal plasma membrane. Upon release at the basal end of the cell, nutrient molecules diffuse into connective tissue space and eventually into capillaries or lacteals of the lamina propria.
The apical surface area of each absorptive cell is greatly increased by evagination into a dense array of microvilli, visible microscopically as the brush border.
In the small intestine, brush border enzymes contribute to digestive breakdown (these enzymes are lacking from absorptive cells of the colon).
The microvilli are supported by an underlying meshwork of microfilaments which comprise the terminal web. At the lateral edges of each cell, the the terminal web reinforces the junctional complex that attaches adjoining cells. (This site is sometimes visible microscopically as a terminal bar at the apical corners of each cell.).
A pale (poorly stained) region above the nucleus indicates the location of the Golgi apparatus, where some absorbed nutrients are processed for transport.
Associated cell types: Interspersed among the many absorptive cells of the intestinal epithelium are scattered goblet cells, occasional enteroendocrine cells (which are difficult to distinguish in routine preparations), and occasional wandering cells of the immune system (e.g., lymphocytes, eosinophils).
The life-span of absorptive cells is short, only a few days. During this time, the cells migrate from deep in crypts, where they are formed by dividing stem cells, to the surface epithelium where they eventually undergo apoptosis. Along villi, this migration is sometimes called "the epithelial escalatory". Look for apoptosis at the tips of villi.
Consult your histology textbook and/or atlas for additional detail and electron micrographs of these cells.
Goblet cells
Goblet cells are scattered among the absorptive cells in the epithelium of the small intestine and colon. These cells are specialized for secretion of mucus, which facilitates passage of material through the bowel. The name "goblet" refers to the cell's shape, narrow at the base and bulging apically.
(Similar cells may also be found in the respiratory and reproductive tracts.)
The apical end of each goblet cell is occupied by a large mass of mucus, which compresses adjacent cells (thus conferring the characteristic "goblet" shape) and displaces the nucleus toward the basal end of the cell. As in other mucous cells, the nucleus is compact and intensely-stained.
Goblet cells comprise an integral part of the epithelium, attached by junctional complexes (evidenced in light microscopy as the "terminal bar") to adjacent absorptive cells.
The proportion of goblet cells to absorptive cells increases along the entire length of the bowel, with relatively few in the duodenum and very many in the colon. The colonic epithelium gives the superficial impression of being almost entirely goblet cells, but there are still several times as many absorptive cells. The goblets are just more conspicuous, with their bulging mucus droplets.
Consult your histology textbook and/or atlas for additional detail and electron micrographs of these cells.
Mucous cells
Cells which are specialized to secrete mucus are called mucous cells. In routine light microscopy, mucous cells are most conspicuously distinguished by their "empty" appearance (i.e., poorly stained cytoplasm) and densely-stained, basal nuclei.
The nucleus in a typical mucous cell gives the impression of having been displaced and compressed by the mass of mucus accumulated in the apical end of the cell.
Mucus does not stain well with standard acidic or basic dyes, but is demonstrated with the Periodic Acid Shiff procedure (PAS stain).
Examples of mucous cells from the GI may be found in salivary glands, esophageal glands, stomach surface, and Brunner's glands of the duodenum. Goblet cells, which stand alone within a surface epithelium, are a characteristic feature of the intestine (as well as the respiratory tract and the female reproductive tract).
Consult your histology textbook and/or atlas for additional detail and electron micrographs of these cells.
Serous Cells
Serous cells, exemplified by pancreatic acinar cells, are specialized for exocrine enzyme secretion.
A serous cell's cytoplasm is visibly polarized, with basophilic basal cytoplasm and variously-staining secretory vesicles (zymogen granules) concentrated in apical cytoplasm. The basal basophilia is due to a concentration of protein synthetic organelles (ribosomes on rough endoplasmic reticulum). The Golgi apparatus is usually located midway along the cell, typically in a supranuclear position.
Examples of serous cells include acinar cells of pancreas and salivary glands, gastric chief cells, and intestinal Paneth cells.
Consult your histology textbook and/or atlas for additional detail and electron micrographs of these cells.
Paneth cells
Paneth cells are secretory cells located at the ends of intestinal crypts. The function for these cells is secretion of anti-bacterial proteins into the crypt lumen, thereby providing protection for the stem cells which line the crypt walls.
Paneth cells have typical serous-secretory appearance, with basophilic basal cytoplasm (containing protein-synthetic rough endoplasmic reticulum) and apical secretory vesicles (zymogen granules).
The secretory vacuoles of Paneth cells contain lysosomal enzymes, with anti-bacterial function.
Consult your histology textbook and/or atlas for additional detail and electron micrographs of these cells.
Myoepithelial cells
Myoepithelial cells are contractile epithelial cells which forcibly express the contents of a gland. Although myoepithelial cells function like smooth muscle, they are typically located within a glandular epithelium, between the secretory cells and the basement membrane. Each myoepithelial cell has long cytoplasmic processes which wrap around a secretory unit. Hence, contraction of the myoepithelial processes can squeeze secretory product from the secretory unit into its duct.
Myoepithelial cells contribute significantly to the secretory activity of sweat glands, salivary glands, and mammary glands.
In routine histological preparations, myoepithelial cells are inconspicuous. The cell body can sometimes be noticed as an "extra" nucleus beneath some secretory cells. The contractile process are thin eosinophilic strands. In routine H&E stained sections of sweat glands, these can often be seen as small pink triangles underlying the secretory cells. In sweat glands and mammary glands, myoepithelial processes are normally difficult to observe without special stains.
· For a nice image of myoepithelial cells (in breast) stained with immunoperoxidase, see WebPath.
Consult your histology textbook and/or atlas for additional detail and micrographs of these cells
The sensation of taste is mediated by elongated sensory cells which occur in clusters called taste buds on fungiform and circumvallate papillae of the tongue. Taste buds interrupt and extend across the tongue's stratified squamous epithelium.
These sensory cells are normally replaced every 10-14 days by division and differentiation of stem cells, which is handy since they are exposed and easily damaged (e.g., by a bite of too-hot pizza).
Associated cell types: In addition to sensory cells, the elongated cells of the taste bud include support cells, which are sometimes (rather pretentiously) called sustentacular cells (from the same root as "sustain"). Stem cells are normally visible in taste buds as shorter cells with round nuclei which appear at the basal end of the tastebud.
Consult your histology textbook and/or atlas for additional detail and electron micrographs of these cells
Hepatocytes
Although all cells are general-purpose metabolic factories, most mature cell types are functionally specialized to play one particular role in the economy of the larger body. In contrast, hepatocytes of the liver are remarkable for the breadth of their "specialization". Among other functions, hepatocytes:
· form and secrete bile
· store glycogen and buffer blood glucose
· synthesize urea
· metabolize cholesterol and fat
· synthesize plasma proteins
· detoxify many drugs and other poisons
· process several steroid hormones and vitamin D
The cellular structure of hepatocytes is correspondingly rich. Instead of displaying a concentration of one particular organelle, hepatocytes have lots of everything -- lots of mitochondria, lots of ribosomes, lots of Golgi bodies, lots of endoplasmic reticulum (both rough and smooth), lots of stored glycogen, lots of lysosomes, lots of plasma membrane (with microvilli on the free surface). They even have lots of nucleus (yes, hepatocytes may be polyploid and commonly have two full-size nuclei).
When an introductory biology book illustrates "the cell", the representative example is often a hepatocyte -- because hepatocytes offer splendid and numerous examples of most cellular organelles.
In appearance, hepatocytes are boxy (cuboidal) cells with one or two large euchromatic nuclei and with abundant, grainy cytoplasm that stains well with both acid and basic dyes (reflecting the abundance of various cellular constituents). Because individual liver cells have an indefinite lifespan, they may accumulate abundant lipofuscin (yellow-brown "wear-and-tear" pigment), especially with advancing age.
Hepatocytes are arranged into cords, in which each hepatocyte is attached to its neighbors in a two-dimensional sheet. On either side of the cord, each hepatocyte faces the space of Disse, across which it communicates freely with adjacent sinusoids.
Hepatocytes are epithelial, but their epithelial nature is expressed in a rather peculiar way.
An ordinary epithelial cell sits on its basal surface, has an apical surface exposed to the external space, and is attached to its neighbors along its lateral surface. In principle, hepatocytes follow this same plan -- but they have a unique topology.
A typical hepatocyte has two basal surfaces, on opposite ends of the cell where it faces the sinusoids on either side of the cord in which it resides.
The apical surface of a hepatocyte occurs along a band around the cell's middle, half-way between the opposing basal surfaces. It is across this surface that bile is secreted. The edges of this apical surface are attached by junctional complexes to those of adjacent hepatocytes, thereby forming the bile canaliculi. These bile canaliculi form a network encircling each hepatocyte and sealed within the hepatic cord. Along this network (which is shaped like chicken-wire), bile can seep toward the periphery of the lobule and hence into the proper bile ducts which are found only portal areas.
(Bile canaliculi are barely visible in routine microscopic preparations, at sites where the boundary between adjacent hepatocytes has been cut neatly and perpendicularly. They can be clearly demonstrated with special stains.)
The lateral surfaces of a hepatocyte take the form of two broad bands which wrap around the cell between the two basal surfaces, separated by the narrow band of apical surface. These lateral surfaces attach the cell to its neighbors within the cord, with junctional complexes sealing off and separating the bile canaliculi (at the apical surface) from the plasma-containing space of Disse (at the basal surfaces).
Consult your histology textbook and/or atlas for additional detail and electron micrographs of these cells.
Endothelial Cells
Endothelial cells are simple squamous cells which line the entire vascular system (including lymphatic channels). Endothelial cytoplasm is inconspicuous in routine light microscopy. Typically only the nuclei are visible, at the boundary between the lumen and the wall of a vessel.
Endothelial nuclei typically appear thin and dark, in cross section. However, occasionally endothelium lies parallel to the plane of section. In this case the nuclei may appear very large, round, and pale.
Although endothelial cells appear rather uninteresting under the microscope, these are important cells. They are situated at a critical location, between the blood and all other body cells. They secrete substances which control local blood flow and blood coagulation, and they are active participants in white blood cell emigration during inflammation.
Continuous endothelium. Throughout much of the body, the capillary endothelial lining is continuous, with neither large gaps between cells nor holes through cells. Materials pass through the endothelium either by diffusion or via rapid vesicular transcytosis. (In most of the brain, a lack of transcytotic vesicles accounts for the blood brain barrier -- the only substances which cross such a barrier are those which can diffuse through plasma membranes or those for which specific membrane channels exist.)
Fenestrated endothelium. In a few special locations -- notably in the sinusoids of the liver, in the glomeruli of the kidney, and in most endocrine glands -- the endothelium is fenestrated (i.e., full of holes -- from fenestra, window). In the liver, where there is also no basement membrane, the fenestrations permit blood plasma to wash freely over the exposed surfaces of the hepatocytes through the space of Disse.
Consult your histology textbook and/or atlas for additional detail and electron micrographs of these cells.
Kupffer Cells (Liver Macrophages)
Kupffer cells are macrophages found in the sinusoids of the liver. These cells have standard macrophage / monocyte specialization (i.e, receptor-mediated phagocytosis, lysosomal digestion). This particular population of macrophages are especially significant, with responsibility not only for cleaning bacteria out of the portal blood stream (the "dirty" blood" from the intestine), but also for removing worn-out red blood cells and recycling hemoglobin (a job shared with macrophages of the spleen).
Kupffer cells are closely associated with the endothelial lining of the liver. Lying along side or draped across the liver sinusoids, the Kupffer cells are not easily distinguished from the endothelial cells.
Historical note: The term reticuloendothelial system refers to the macrophages of the liver, spleen and lymph nodes, i.e., those organs with elaborate endothelially-lined channels supported by reticular connective tissue. The name reflects former confusion about the distinction between endothelial cells and the scattered population of macrophages (monocytes, histiocytes). Macrophages can be readily labelled experimentally through their phagocytosis of injected carbon particles. However, endothelial cells are also labelled by the same procedure. Although endothelial cells are not dramatically phagocytotic, they do shuttle some materials across the endothelial lining via small endocytotic and exocytotic vesicles.
Consult your histology textbook and/or atlas for additional detail and electron micrographs of these cells.
Gastric Surface Mucous Cells
The protective cells which line the surface of the stomach (including gastric pits) are called surface mucous cells. These cells are critical for resisting attack by digestive acid and enzymes.
Any disruption of these cells' function can lead to an ulcer. See WebPath (low mag), WebPath (high mag), or Milikowski & Berman's Color Atlas of Basic Histopathology, pp. 240-241.
The appearance of surface mucous cells is rather different from that other mucous cells
Individual surface mucous cells also differ in shape from intestinal goblet cells. Since the mucosal surface of the stomach consists of these cells and no others, individual surface mucous cells cannot bulge apically like the goblet cells.
Parietal cells
(oxyntic
cells) of the stomach secrete acid,
by pumping hydrogen ions across the cell membrane. These are among the
most dramatically differentiated epithelial cells in the body, with functional
specialization
reflected in their microscopic appearance. Chief cells of the stomach secrete the
digestive enzymes (pepsins) of the stomach and have typical serous-secretory
appearance. Mucous neck
cells of
the stomach are
inconspicuous cells with a typical mucous-secretory
appearance. These cells are most common in the upper ("neck") region of
the fundic glands (i.e., near to the glands' openings into the bottoms of gastric pits).
Their specific function remains unclear. Mucous neck
cells are difficult to identify in routine sections of stomach mucosa. When the
cells are neatly cut from top to bottom, they can be recognized by the basally
compressed (often wedge-shaped) nucleus and the stored mucus that fills the
apical cytoplasm. But in other random planes of section, the
poorly-stained mucus is inconspicuous and the nucleus can resemble any of the
small dense nuclei found in lamina
propria. Endocrine
Cells Many of
the body's cells secrete substances which influence other cells, either locally
or at some distance. Cells generally regarded as endocrine cells are those
which are conspicuously specialized for this function. The gastrointestinal system
has two classes of such cells, the islets of Langerhans in
the pancreas
and the enteroendocrine cells in the mucosal epithelium of the stomach and intestine. Pancreatic islets are covered elsewhere. Microscopically,
stem cells lack distinguishing characteristics. However, their activity
can be detected by the presence of mitotic figures, the intensely basophilic
masses of condensed chromation which characterizes cells undergoing mitosis.
Stem cells of the intestinal mucosa line
the walls of the crypts and
continually replenish the intestinal epithelium, completely replacing all the absorptive
cells and goblet
cells approximate once every four days. These cells are inconspicuous
when resting, but mitotic figures (intensely basophilic condensed chromatin) are
common and easily noticed in the crypts of the small intestine. Consult
your histology or cell biology textbook for additional information about stem
cells.
Link to the endocrine
system.
What
causes the bleeding problem?
low
glycoprotein Ib, IX, and V levels
platelets
unresponsive to ristocetin in vitro
giant bizarre
platelets (mean diameter = 5-6 microns)
Loading
dose: 100-200 mg/kg PO/IV | |
C -
Safety for use during pregnancy has not been established.
| |
Documented
hypersensitivity; platelet-type von Willebrand disease
| |
Not
established, limited data exist; administer as in adults
| |
C -
Safety for use during pregnancy has not been established.
| |
BRANCHIAL
(PHARYNGEAL) CYSTS AND FISTULAS
DEVELOPMENT
OF THE THYROID AND THYROGLOSSAL DUCT CYSTS
muscles of
facial |
(Reichert's
Cart.) | ||
Description:
Seizuresmay
occur very frequently and then go unnoticed for months or
years. causes
diag
trt
Similart
condition Complex
partial Seizures Febrile
Seizures Ethosuximide is indicated for this
type (but no other type) of seizure. Other drugs used in the treatment
of absence seizures are valproic acid, clonazepam, and a new agent,
lamotrigine. |
Anticonvulsant
The control of absence (petit mal) epilepsy.
Contraindications
Ethosuximide
should not be used in patients with a history of hypersensitivity to
succinimides.
Precautions
Blood
dyscrasias, including some with fatal outcome, have been reported to be
associated with the use of ethosuximide; therefore, periodic blood counts should
be performed. Ethosuximide is capable of producing morphological and functional
changes in the animal liver. In humans, abnormal liver and renal function
studies have been reported. Administer ethosuximide with extreme caution to
patients with known liver or renal disease. Periodic urinalysis and liver
function studies are advised for all patients receiving the drug. Cases of
systemic lupus erythematosus have been reported with the use of ethosuximide.
The physician should be alert to this possibility.
Ethosuximide may
impair the mental and/or physical abilities required for the performance of
potentially hazardous tasks, such as driving a motor vehicle or other such
activity requiring alertness; therefore, caution the patient accordingly.
Ethosuximide, when used alone in mixed types of epilepsy, may increase the
frequency of generalized tonic-clonic attacks in some patients.
Proceed
slowly when increasing or decreasing dosage, as well as when adding or
eliminating other medication. Abrupt withdrawal of anticonvulsant medication may
precipitate petit mal status.
Gastrointestinal:
Gastrointestinal symptoms occur frequently and include
anorexia, vague gastric upset, nausea and vomiting, cramps, epigastric and
abdominal pain, weight loss, and diarrhea.
Hemopoietic:
Leukopenia, agranulocytosis, pancytopenia, aplastic
anemia, eosinophilia.
Nervous system:
Neurologic and sensory reactions reported during therapy
with ethosuximide have included drowsiness, headache, dizziness, euphoria,
hiccups, irritability, hyperactivity, lethargy, fatigue, and ataxia. Psychiatric
or psychological aberrations associated with ethosuximide administration have
included disturbances of sleep, night terrors, inability to concentrate, and
aggressiveness. These effects may be noted particularly in patients who have
previously exhibited psychological abnormalities. There have been rare reports
of paranoid psychosis, increased libido, and increased state of depression with
overt suicidal intentions.
Integumentary:
Dermatologic manifestations which have occurred with the
administration of ethosuximide have included urticaria, Stevens-Johnson
syndrome, systemic lupus erythematosus, and pruritic erythematous rashes.
Genitourinary:
Microscopic hematuria.
Miscellaneous:
Myopia, vaginal bleeding, swelling of the tongue, gum
hypertrophy, hirsutism.
Question
20: BIO GP
In
the family shown above, individuals affected with profound deafness are
represented by a shaded symbol. The
phenotypes of individuals in the fourth generation can best be explained by:
A. autosomal dominant inheritance
B. locus
heterogeneity
C. mitochondrial inheritance
D. multifactorial
inheritance
E. X-linked dominant inheritance
The correct answer is:
B.
Description: |
Question
21: PHYSIO CV
At which point on the diagram above would the length of the
myocardial sarcomere be approximately 2 mm with maximal actin-myosin cross
bridging?
A. A
B. B
C. C
D.
D
E. E
. The correct answer is: B.
Description: |
Law of
A.As
ventricular volume increases, ventricular circumference increases and lengths of
individual cells increase B.At constant volume,
increased intraventricular pressure causes increased tension in the individual
cells of the ventricular muscle
C. As
ventricular volume increases, a larger force from each muscle cell is required
to produce any given intraventricular pressure
D. Pressure
(P) = 2 x tension (T) x Wall thickness (H)/intraventricular radius
(r)
1. Filling
Phase (Fig.1, A-B):radius increases at constant filling
pressure causing increased wall tension (stretch)
2.
Isovolumetric Contraction (Fig.1, B-C):Tension
increases at constant radius causing increased pressure
3. Ejection
Phase (Fig.1, C-D):Radius decreases at constant tension
causing further increase in pressure
4.
Isovolumetric Relaxation Phase (Fig.1, D-A):Tension
decreases at constant radius causing decreased pressure.
Excitation - Contraction Coupling:
A.
Activation:1.Calcium couples electrical events to the
subsequent mechanical events. 2.Contraction of cardiac
muscle is absolutely dependent on the presence of extracellular as well as
intracellular Ca2+ stores.
3.Transporters mediating
movement of calcium into the cytosol.
a. The Ca
channel and the SR-Ca release channel:i.)The Ca channel in heart is related to
the DHP receptor in skeletal muscle (SKM). ii.)The
cardiac Ca channel is not physically connected to the Ca-release channel in the
SR.
iii.) Ca
entering through the Ca channel induces opening of the SR Ca-release channel.
This process is referred to as Ca-induced Ca-release.
b. The Na-Ca
exchanger:
i.)Exchanges 1 Ca2+ for 3 Na+. ii.)The
magnitude of the Na+ and Ca2+ gradients and the membrane potential (m.p.)
determine the direction of net Ca flux, as mediated by the
exchanger.
iii.)[Na+]o, [Na+]i, [Ca2+]o are constant on a beat-to-beat
basis.
iv.)[Ca2+]i varies between 0.1 and 10 mM; membrane potential varies
between -85 and +20mV.
v.)Exchanger
mediates Ca2+ efflux at rest.
vi.)Exchanger
mediates Ca2+ influx during early part of the action potential but net efflux as
[Ca2+]i and m.p. change.
B.
Relaxation:
1. SR
Ca-ATPase sequesters Ca into the SR 2. Na-Ca exchanger mediates Ca2+
efflux
3.
Sarcolemmal Ca-ATPase mediates Ca efflux
4.An amount of
calcium equal to that which entered must exit the cell on a beat-to-beat basis
if steady state is to be maintained.
II.
Determinants of Cardiac Contractile Force:
A.
Contractility:
Contractility
(force of contraction) is enhanced when the sensitivity of the filaments for
calcium and/or calcium availability are enhanced. 1. Contractility and the
Autonomic Nervous system:a. Sympathetic: Norepinephrine
and epinephrine enhance Ca2+ entry through Ca-channels and Ca-ATPase activity
causing enhanced calcium cycling. These neurotransmitters also alter heart rate
(see below). b. Parasympathetic: ACh decreases Ca entry through Ca channels by
counteracting the processes underlying sympathetic effects. These
neurotransmitters also alter heart rate (see below).
2. Heart
rate:
a.An increase
in heart rate leads to an increase in calcium content of the SR. This enhances
Ca-induced Ca-release, calcium availability, and contractile force (positive
staircase, Bowditch effect). b.A decrease in heart rate
leads to a decrease in calcium content of the SR, which decreases Ca-induced
Ca-release, calcium availability, and contractile force.
3. Cardiac
Glycosides(digoxin, digitoxin, ouabain, digitalis)
inhibit the Na,K ATPase. This causes the transmembrane Na gradient to decrease,
which diminishes the ability of the Na-Ca exchanger to pump calcium out of the
cell. The net effect is an increase in calcium content of the SR and an increase
in contractile force.
B.
Length-tension relationships - isometric relationships:
1. The
basics of actin-myosin interaction in heart are comparable to SKM &endash;
i.e. sarcomere length determines thick-thin filament
interactions and therefore force production. 2. The "length" of cardiac
muscle cells is determined by the volume of blood in the chambers of the heart,
which in turn is determined by filling pressure (preload).
3.Since the force
of contraction of the heart is typically measured as pressure, the
length-tension relationship in heart is usually measured as a pressure-volume
relationship.
4.The
relationship between pressure and volume was first described by Frank and
Starling and is now referred to as the Frank-Starling relationship or Starling's
law of the heart.
III.
Pressure Volume Loops:
A. During
the cardiac cycle, volume is not constant therefore length is not constant B.
The volume in the ventricle at the onset of ventricular contraction is the End
Diastolic Volume (EDV). The pressure required to establish this volume is the
preload. The relationship between preload and EDV corresponds to the
"rest-tension curve".
C.The
ventricle must develop sufficient pressure to exceed that in the aorta before
ventricular volume can decrease during the cardiac cycle. Aortic pressure during
ejection is the afterload. If no volume can be ejected because the heart cannot
develop sufficient pressure to exceed the aortic pressure, then the heart
contracts isometrically.
D. Left
ventricular function throughout the cardiac cycle can be visualized as a
pressure volume loop, which relates the two pressure volume
relationships.
1.The volume in
the ventricle at the end of diastole is the end diastolic volume (EDV). Shortly
after ventricular contraction begins, the mitral valve closes and the ventricle
contracts isovolumetrically until intraventricular pressure exceeds aortic
pressure. 2.Ejection begins as pressure in the
ventricle exceeds that of the aorta and the aortic valve opens. Pressure
continues to rise early during ejection but then falls late in ejection (see Law
of La Place).
3. When
ventricular pressure falls below aortic pressure, the aortic valve closes and
isovolumetric relaxation ensues.
4. When
ventricular pressure falls below atrial pressure the mitral valve opens and the
filling phase begins. Shortly after filling begins, the ventricular
pressure-volume relationship intersects and travels along the "rest-tension"
curve.
5.The heart
operates on the ascending limb of the active tension relationship, which insures
heterometric reserve (ability to contract harder if volume increases suddenly)
and the capacity to match input and output on a beat to beat basis.
Question
22: BIO GP
Absence
of which of the following enzymes would impair the rate-limiting step of
glycogenolysis?
A. alpha-1,4-glucan
transferase
B. Glycogen phosphorylase
C. Glycogen
synthase
D. Phosphoglucomutase
E. UDP-glucose
pyrophosphorylase
. The correct answer is: B.
Description: Table
1. Glucose Estimation by GOD/POD
Table
2. Table of Enzymes
|
Reactions
of Glycolysis
First step
of glycolysis is glucose transport (facilitated diffusion) across the sarcolemma
that is accomplished by a specific protein on the plasma membrane–requires
insulin during resting states.
1.
phosphoryl transfer (phosphate group
attached to the sixth carbon)
|
ATP-Mg2+
––> ADP |
|
glucose |
—————————> |
glucose
6-phosphate |
|
hexokinase |
|
2.
isomerization
glucose-6-phosphate |
—————————> |
fructose
6-phosphate |
3.
phosphoryl transfer (phosphate group
attached to the first carbon)
|
ATP-
Mg2+ ––>
ADP |
|
fructose
6-phosphate |
—————————> |
fructose
1,6-diphosphate |
|
phosphofructokinase |
|
4.
splitting of six-carbon compound into two
three-carbon compounds (phosphate group is attached to third carbon of each
compound)
fructose
1,6-diphosphate |
—————————> |
2
glyceraldehyde 3-phosphate |
5.
reduction of NAD+
|
Pi
+ NAD+ ––> NADH
+ H+ |
|
glyceraldehyde
3-phosphate |
—————————> |
1,3-diphosphoglycerate |
6.
formation of ATP
|
ADP
+ Pi ––> ATP |
|
1,3-diphosphoglycerate |
—————————> |
3-phosphoglycerate |
7.
phosphoryl shift
3-phosphoglycerate |
—————————> |
2-phosphoglycerate |
8.
dehydration (release of H2O)
2-phosphoglycerate |
—————————> |
phosphoenolpyruvate
+ H2O |
9.
formation of ATP
|
ADP
+ Pi ––> ATP |
|
phosphoenolpyruvate |
—————————> |
pyruvate |
|
pyruvate
kinase |
|
10. reduction of pyruvate (two
possibilities)
|
NADH
+ H+ ––>
NAD+ |
|
a)
pyruvate |
—————————> |
lactate |
|
lactate
dehydrogenase |
|
|
NAD+
––> NADH + H+ |
|
b)
pyruvate + Coenzyme A |
—————————> |
acetyl
Coenzyme A + CO2 |
|
pyruvate
dehydrogenase |
|
Glycogenolysis
|
phosphorylase |
|
[glucose]n
+ Pi |
<—————————> |
glucose
1-P + [glucose]n-1 |
glucose
1-P |
—————————> |
glucose
6-P |
Regulation of
glycogenolysis
|
+
cAMP, Ca2+, ADP, AMP, IMP, Pi |
|
phosphorylase
b (inactive) |
<—————————————> |
phosphorylase
a (active) |
|
--
ATP,G
6-P, H+ |
|
Glycogenesis
glucose
6-P |
<—————————> |
glucose
1-P |
glucose
1-P |
—————————> |
UDP-glucose |
|
glycogen
synthase (active) |
|
UDP-glucose
+ [glucose]n |
<—————————> |
UDP +
[glucose]n+1 |
Regulation of
glycogenesis
|
+
cAMP, Ca2+ |
|
glycogen
synthase (active) |
<—————————> |
glycogen
synthase (inactive) |
|
--
insulin |
|
Regulation
of Glycolysis
Adenine
nucleotide energy charge
= |
[ADP] + 2 [ATP] |
X
0.5 |
|
[AMP]
+ [ADP] + [ATP] |
|
·
if all
adenine is in the form of ATP, the energy charge is 1.0; if all adenine is in
the form of AMP, the energy charge is 0.0; energy charge is usually
~0.8
Phosphofructokinase
(PFK)
Stimulators |
Inhibitors |
ADP |
ATP |
Pi |
CP |
AMP |
H+ |
NH4+ |
citrate |
increased
temperature |
|
Lactate
dehydrogenase (LDH)
Hexokinase
Question
23: BESCI GP
A
34-year-old female is brought to her family physician by her
brother. He states
that the patient's husband had run away with another woman the previous day.
After discovering this, the patient arrived at her brother's home in a "dazed
state," was unable to function appropriately the remainder of the evening, and
slept fitfully all night. Early in the morning she began to talk to people who
were not present, and debated whether or not to kill her children and herself.
He denies anything like this ever happening before. Which of the following is
the most likely diagnosis?
A. Bipolar disorder
B. Brief
psychotic disorder
C. Schizoaffective disorder
D.
Schizophrenic disorder
E. Schizophreniform disorder
The correct
answer is: B.
Description: Brief
Psychotic Disorder Brief
Psychotic Disorder is a psychosis that has a rapid onset, generally
following a major stressor. Its hallmark is emotional turmoil, mood
lability, and confusion. The sufferer must have one of the following
symptoms: delusions, hallucinations, grossly disorganized or catatonic
behavior, or disorganized speech. A brief psychotic episode is time
limited, lasting at least a day, but less than a month. As a rule, the
quicker the onset, the faster the recovery.
acute psychotic episode lasting longer than one
day but less than one month
SYMPTOMS
Presence
of one (or more) of the following symptoms: (a)
delusions Note: Do not
include a symptom if it is a culturally sanctioned response pattern.
Duration of
an episode of the disturbance is at least 1 day but less than 1 month,
with eventual full return to premorbid level of functioning.
The
disturbance is not better accounted for by a Mood Disorder With Psychotic
Features, Schizoaffective Disorder, or Schizophrenia and is not due to the
direct physiological effects of a substance (e.g., a drug of abuse, a
medication) or a general medical condition.
|
Old
term: Brief Reactive Psychosis
Associated
Features
Diagnostic
Criteria
·
With
Marked Stressor(s) (brief
reactive psychosis): if symptoms occur shortly after and apparently in response
to events that, singly or together, would be markedly stressful to almost anyone
in similar circumstances in the person's culture
·
Without
Marked Stressor(s): if
psychotic symptoms do not occur shortly after, or are not apparently in response
to events that, singly or together, would be markedly stressful to almost anyone
in similar circumstances in the person's culture
·
With
Postpartum Onset: if
onset within 4 weeks postpartum
Differential
Diagnosis
Some
disorders have similar or even the same symptom. The clinician, therefore, in
his diagnostic attempt has to differentiate against the following disorders
which he needs to rule out to establish a precise
diagnosis.
·
Psychotic
Disorder Due to a General Medical Condition or a Delirium;
·
·
Substance-Induced
Psychotic Disorder;
·
Substance-Induced
Delirium and Substance Intoxication;
·
Mood
Episode;
·
Schizophreniform
Disorder;
·
Delusional
Disorder;
·
Mood
DisorderWithPsychotic Features;
·
Psychotic
Disorder Not Otherwise Specified;
·
Factitious
Disorder, With Predominantly Psychological Signs and Symptoms;
·
Malingering;
·
Personality
Disorders.
Antipsychotics
|
Dose
|
Anti- |
EPS² |
Sedation |
Hypotension |
Chlorpromazine |
100-2000 |
++++ |
++ |
+++++ |
+++++ |
Thioridazine
|
100-600 |
+++++ |
+ |
++++ |
+++++ |
Trifluoperazine |
5-60 |
++ |
++++ |
+ |
++ |
Thiothixene
|
5-60 |
++ |
++++ |
++ |
++ |
Fluphenazine
|
5-30 |
++ |
+++++ |
++ |
++ |
Haloperidol
|
2-200 |
+ |
+++++ |
++ |
+ |
Antipsychotics
|
Dose
|
Anti- |
EPS² |
Sedation |
Hypotension |
Risperidone
|
1-6 |
+ |
+ |
+ |
++ |
Olanzapine
|
5-20 |
+ |
+ |
++ |
+ |
Clozapine³
|
5-60 |
+++++ |
+ |
+++++ |
+++++ |
¹ Dry
mouth, constipation, blurred vision, urinary retention.
²
Extrapyramidal side effects (dystonia, parkinsonism,
akathisia, tardive dyskinesia).
³
Requires weekly White Blood Cell (WBC) count because of risk of agranulocytosis.
Adapted
from Bernstein JG: Handbook of drug therapy in psychiatry, ed 3,
Special
Antipsychotic Adverse Reactions
Schizophreniform
Disorder
For a
material part of at least one month (or less, if effectively treated) the
patient has had 2 or more of:
Delusions
(only one symptom is required if a delusion is bizarre, such as being abducted
in a space ship from
the sun).
Hallucinations
(only one symptom is required if hallucinations are of at least two voices
talking to one another or of a voice that keeps up a running commentary on the
patient's thoughts or actions)
Speech
that shows incoherence, derailment or other disorganization
Severely disorganized or catatonic behavior.
Any negative symptom such as flat affect, muteness, lack of
volition.
Including
prodromal, active and residual phases, an episode of the illness has lasted at
least one month but not longer than 6 months.
Mood and
schizoaffective disorders have been ruled out, because the duration of any
depressive or manic episodes that have occurred during the psychotic phase has
been brief.
This
disorder is not the direct physiological result of a general medical condition
or the use of substances, including prescription medications.
A
statement of prognosis should be added to the diagnosis:
With Good
Prognostic Features (2 or more of the following):
Actual
psychotic features begin within 4 weeks of the first noticeable change in the
patient's functioning or behavior.
The
patient is confused or perplexed when most
psychotic.
Premorbid
social and job functioning are good.
Affect
is neither blunt nor flattened.
Associated
Features:
Learning
Problem
Hypoactivity
Psychosis
Euphoric Mood
Depressed Mood
Somatic or Sexual Dysfunction
Hyperactivity
Guilt or Obsession
Sexually Deviant Behavior
Odd/Eccentric or Suspicious Personality
Anxious or Fearful or Dependent Personality
Dramatic or Erratic or
Antisocial Personality
Differential
Diagnosis:
Some
disorders have similar or even the same symptom. The clinician, therefore, in
his diagnostic attempt has to differentiate against the following disorders
which he needs to rule out to establish a precise diagnosis.
Schizophrenia;
Brief Psychotic Disorder.
Cause:
This
diagnosis is used when the initial signs of schizophrenia are present. Psychotic
symptoms can dissipate after a short period and never return for some people
And because significant stressors and substance use can
bring about psychotic symptoms, this diagnosis is used for the first six months.
If symptoms persist after six months, then a diagnosis of Schizophrenia is
given.
Schizophreniform
disorder appears to be related to abnormalities in the structure and chemistry
of the brain, and appears to have strong genetic links; but its course and
severity can be altered by social factors such as stress or a lack of support
within the family. The cause of schizoaffective disorder is less clear cut, but
biological factors are also suspected
Treatment:
Medication
is the most important part of treatment as it can reduce and sometimes eliminate
the psychotic symptoms. Case management is often needed to assist with daily
living skills, financial matters, and housing, and
therapy can help the individual learn better coping skills and improve social
and occupational skills
Question
24: PATH REPRO
A 34-year-old woman presents with abdominal pain and reports
changes in her bowel habits. On pelvic examination a mass is palpated on her
right ovary. Laparoscopic surgery is performed and the mass is removed. The
gross appearance of the tumor is shown below. What type of tumor is it?
these are the
type of picture seen during the usmle where nothing is certain and too
dark
A.
Choriocarcinoma
B. Dysgerminoma
C. Fibroma
D.
Granulosa-theca cell
E. Teratoma
The correct answer is:
E.
Description: |
OVARIAN
TERATOMA |
| |
Germ
cell tumors represent 15-20% of ovarian tumors. Germ cell tumors consist
of teratomas, dysgerminoma, endodermal sinus tumor, choriocarcinoma,
embryonal carcinoma, polyembryoma and mixed germ cell tumors.
Hitogenesis of the
ovarian germ cell tumors DISTINCTIVE FEATURES
Appear
in three forms. Mature (benign) teratomas (dermoid cyst), Immature
(malignant) teratomas, and monodermal or specialized teratomas.
MATURE
(BENIGN) TERATOMA: Benign
teratomas are bilateral in 10-15% of cases.
IMMATURE
(MALIGNANT) TERATOMA: Rare
tumors. MONODERMAL
(SPECIALIZED) TERATOMA: The
cells in these tumors grow along a single germ cell layer. Examples
include struma ovarii which consists of mature thyroid tissue and ovarian
carcinoid. | ||
Question
25: PHARM GP
A
55-year-old woman is receiving chemotherapy for non-Hodgkin's
lymphoma. Several
days after a treatment, she notes that she has blood in her urine. Which of the
following antineoplastic drugs is most likely responsible for this side effect?
A. Bleomycin
B. Cisplatin
C.
Cyclophosphamide
D. Doxorubicin
The correct answer is:
C.
Description: |
Plicamycin(Mithramycin)
Mechanism
of action:binds to DNA -- interrupts DNA-directed RNA
synthesis
Also
decreases plasma calcium (independent tumor cell action;acts on osteoclasts)
Clinical
Uses:
some
efficacy in testicular cancer that is unresponsive to standard
treatment:
especially
useful in managing severe hypercalcemia associated with
cancer
Adverse
Effects:
nausea
vomiting
thrombocytopenia
leukopenia
hypocalcemia
liver
toxicity
bleeding
disorders