UNIT-1 Genetic disorders

presented by jayad khan & shah sawar

4TH Semester
INS-KMU Peshawar
objectives:
 discuss trisomy, monosomy, polysomy and other related terminologies to genetic disorders.
 defferentiate between genetic and congenital disorders.
 Explain the chromosomal defect with special emphasis on aneuploidy .
 discuss the pathophysiology and clinical manifestation of Down’s syndrome.
Genetics:

• Genetics is a branch of biology concerned with the study of genes,genetic variations and heridity in
organism.
• Genes:
• Segment of DNA responsible for a particular trait.
• Trait:
• A physical charicteristics or attributes.
• What both alleles eventually code for , so trait can be height of the person ,color of the eyes ,
color of the skin or color of the hair etc.
– Gene locus = where it’s located on the chromosome.
– Alleles: Genes that have the same locus (location) on homologus chromosome and doing
the similer function these are called alleles .
History of genetics:

• The scientific history of genetics began with the works of Gregor Mendel in the mid-19th century.
• the word gene was first used by Wilhelm Johannsen in 1909, based on the concept developed by
Gregor Mendel in 1866 (Mendel 1866).
• Gregor Mendel, through his work on pea plants, discovered the fundamental laws of inheritance. He
deduced that genes come in pairs and are inherited as distinct units, one from each parent. Mendel
tracked the segregation of parental genes and their appearance in the offspring as dominant or
recessive traits.
Conti...

• DNA:
• linear chain unbranched polymer of nucleotides containing the total life formate .
• made up of nitrogeniuos bases, pentose suger and phosphoric acid .
• breaks by endonucleasis and exonucleasis
• chromosome:
• made up of DNA and histone protein .
• Chromosomes components
– Chromatid

– Centromere

– Short arm and long arm

conti...

• chromatids:
• each of the two thread like strands into which a chromosome devide longitudinaly during cell devision .
• Centromere:
• The point on a chromosome by which it is attached to a spindle fiber during cell division.
• The human genome has just over 3 billion DNA base pairs encoding 750 MB of information and
containing 20,000-25,000 protein- coding genes.
• Homologus chromosome :
• corresponding chromosome from mother and father having same genetic materials are homolugus to
each other .
• X and Y are not homololugus to each other because they having no same genetic materials.

• Diploid : When one’s chromosomes are in matched pairs (2n)

– One chromosome in the matched pair ---- from the father
– One chromosome in the matched pair from the mother
 What are dominant and recessive alleles?

• Since human cells carry two copies of each chromosome? they have
two versions of each gene?. These different versions of a gene
are called alleles
• Alleles can be either dominant? or recessive
• Dominant alleles show their effect even if the individual
only has one copy of the allele (also known as being
heterozygous?). For example, the allele for brown eyes is
dominant, therefore you only need one copy of the 'brown
eye' allele to have brown eyes (although, with two copies
you will still have brown eyes).
• Recessive alleles only show their effect if the individual has
two copies of the allele (also known as being homozygous?).
For example, the allele for blue eyes is recessive, therefore to
have blue eyes you need to have two copies of the 'blue
eye' allele.
conti...
Defference betweeen genetic and congenital disorder

• Genetic disease: Resulting from a chromosome abnormality or a defective gene.

• A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially
a condition that is present from before birth. Most genetic disorders are quite rare and affect
one person in every several thousands or millions.
• Congenital disease:
• Abnormality present at birth, even though it may not be detected until some time after birth.
• it occures during intra -uterine OR in fatal life , due to some toxic substances and environmental factors
Classification of Genetic Disorders:

 Autosomal dominant
 Autosomal recessive
 X-linked dominant
 X-linked recessive
 Y-linked
 Mitochondrial
Dominant Diseases:

• These genetic diseases only require a single copy of the gene to be damaged. This error need only
be inherited from one parent in order to get the disease. The bad gene from one parent
dominates the other parent's good gene. There is no such thing as a "carrier" of a dominant disease
because everyone who has the genetic error gets the disease.

• Recessive diseases:
• These are diseases where both copies of a gene must be damaged or mutated. In other words,
the genetic error usually needs to be inherited from both parents to get the disease. Inheriting this
gene error from only one parent usually causes the person to be a "carrier" of the disease, still
having the genetic error, but without any diseases or symptoms.
Autosomal Dominant:

• Dominant conditions are expressed in individuals who have just one copy of the mutant allele.
The transmission of an autosomal dominant trait. Affected males and females have an
equal probability of passing on the trait to offspring.

• Examples:
• Huntington Disease:
– Huntington's disease, chorea, or disorder (HD), is a progressive
neurodegenerative genetic disorder, which affects muscle coordination
• Acondroplasia (short-limbed dwarfism)
• Polycystic kidney disease:
– Kidney disease characterized by enlarged kidneys containing many
cysts; often leads to kidney failure.
Autosomal recessive :

• To understand what autosomal recessive inheritance means you

• first need to break down the words:

• Autosomal – This means the disease affects both males and females equally.

• Recessive – This means both parents must be a carrier for a child to be at risk although
the parents themselves (the carriers) are not affected by the disease.

• Inheritance – This means the process of genetic transmission of characteristics.

conti...

• Recessive conditions are clinically manifest only when an individual has two copies of the
mutant allele. When just one copy of the mutant allele is present, an individual is a carrier of
the mutation, but does not develop the condition.

• Females and males are affected equally by traits transmitted by autosomal recessive
inheritance. When two carriers mate, each child has a 25% chance of being
homozygous wild-type (unaffected); a 25% chance of being homozygous mutant
(affected); or a 50% chance of being heterozygous (unaffected carrier).
• Examples of Autosomal Recessive
• Cystic fibrosis: Is an inherited disease of the secretary glands. Secretary
• glands include glands that make mucus and sweat.
• Hemochromatosis: Hereditary hemochromatosis is an inherited
• (genetic) disorder in which there is excessive accumulation of iron in the body (iron overload). It is a
common genetic disorder
conti...

• Phenylketonuria (PKU):
• PKU is caused by a mutation in a gene on chromosome 12. The gene codes for a protein
called PAH (phenylalanine hydroxylase), an enzyme in the liver. This enzyme breaks down
the amino acid phenylalanine into other products the body needs.

• X-Linked Disorders:

• One normal copy (green x) of a gene on the X chromosome is generally

sufficient for normal function. Women who have a defective gene (red x) on
one of their two
• X chromosomes are protected by the normal copy of the same gene on the
second chromosome. But men lack this protection, since they have one X and
one Y chromosome.
conti...

• Each male child of a mother who carries the defect has a 50 percent risk of inheriting the faulty
gene and the disorder. Each female child has a 50 percent chance of being a carrier like her mother.
Y – Link disorder:

• Y-linked disorders are caused by mutations on the Y chromosome. Because males

inherit a Y chromosome from their fathers, every son of an affected father will be affected. Because
females only inherit an X chromosome from their fathers, and never a Y chromosome, female
offspring of affected fathers are never affected.

• Since the Y chromosome is relatively small and contains very few genes, relatively few Y-linked
disorders occur. Often, the symptoms include infertility. Examples are male infertility.
Mitochondrial Disorder:

• This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial
DNA. Because only egg cells contribute mitochondria to the developing embryo, only mothers can
pass on mitochondrial conditions to their children. An example of this type of disorder is
hereditary optic neuropathy , diabetes mellitus and deafness.

• The primary function of mitochondria is conversion of molecule into usable energy. Thus many
diseases transmitted by mitochondrial inheritance affect organs with high-energy use such as
the heart, skeletal muscle, liver, and kidneys.
Trisomy, Monosomy, Polysomy

• Trisomy:
• Trisomy refers to the presence of three copies, instead of the normal two, of a particular
chromosome. The presence of an extra chromosome 21, which is found in Down syndrome, is
called trisomy 21. Trisomy 18 and Trisomy 13, known as Edwards Syndrome and Patau
Syndrome, respectively, are the two other autosomal trisomies recognized in live-born
humans. Trisomy of the sex chromosomes is possible, such as in (47,XXX), (47,XXY), and (47,XYY)

• Monosomy:
• The condition of having a diploid chromosome complement in which one chromosome lacks its
homologous partner.

•
conti..

• Polysomy:

• Is a condition in which an organism has at least one more chromosome than normal, i.e., there may be
three or more copies of the chromosome rather than the expected two copies.

• Aneuploidy?

• the presence of abnormal number of chromosome in a cell ,which can result from the loss or gain of
one chromosome or more chromosome
• There may be fewer chromosomes, as in Turner's syndrome (one X chromosome in females), or more
chromosomes, as in Down syndrome (three copies of chromosome 21).
conti...

• Such individuals have various abnormal physiologic and morphologic traits.

• Aneuploidy is a cellular condition in which instead of two chromosomes, you have either a missing or
extra chromosome for one of the autosomes (1 – 22) or sex chromosomes. A variety of genetic
abnormalities that cause problems can be traced to Aneuploidy?
• Examples:
• Trisomy 13 (Patau syndrome)
• Trisomy 21(Down syndrome
• Trisomy 18 (Edward syndrome)
Conti...

• Can occur with sex chromosomes too; if a person is missing all or part of the X chromosome
(XO, instead of XX chromosome) they will be female but suffer from turner syndrome and
may have many health conditions, including infertility. Klinefelter’s is a condition in male where they
have an extra X chromosome (XXY).
 Down syndrome

• Down syndrome is a chromosomal disorder caused by an error in cell division that results in an extra
21st chromosome. The condition leads to impairments in both cognitive ability and physical growth that
range from mild to moderate developmental disabilities.

• Through a series of screenings and tests, Down syndrome can be detected before and after a baby is
born.
• It is named after John Langdon Down, the British doctor
• who described the syndrome in 1866.
• The disorder was identified as a chromosome 21 trisomy by Jérôme Lejeune in 1959.
Down Syndrome
Pathophysiology

• Trisomy 21 (Non-disjunction):
• The most common cause of Down syndrome (about 95% of cases) is trisomy 21, which
results from a non-disjunction event during cell division. Normally, during the formation of
reproductive cells (sperm and egg), the chromosomes separate into equal groups. In the
case of trisomy 21, an error occurs during cell division, and a pair of chromosome 21 fails to
separate properly. As a result, one of the reproductive cells ends up with an extra copy of
chromosome 21, leading to a total of three copies instead of the usual two.

• Translocation: In about 3-4% of cases, Down syndrome is caused by a

translocation, where part of chromosome 21 breaks off and attaches itself to another
chromosome. In this scenario, individuals still have the usual two copies of
chromosome 21, but the extra genetic material is present on another chromosome.
If one of the parents carries this translocation, there is an increased risk of having a
child with Down syndrome.
Clinical manifestation

• Small stature and short neck

• Flat nasal bridge
• Single, deep creases across the center of the palm
• Large tongue small mouth
• Large space between large and second toe
• Congenital heart defects
• Spacing abnormality of the teeth
• High arch palate
Conti...

• Mental retardation
• Muscle weakness and hypotonia
• Growth retardation
• Small nose

• (Transverse (simian) palmar crease

Prepared and presented by
Abdul Hafeez,
Bsn 4th semeser,
INS KMU Peshawar.
Objectives:
 Alterations in chromosome structure.
 Patterns of chromosomes breakage and
rearrangements.
INTRUDUCTION
• Any type of change in structure of a normal chromosome, is
referred to Structural Chromosomal aberration. These changes are
also known as chromosomal mutations or structural chromosomal
changes.
 It may take place in both somatic as well as in germ cells.
 It occurs during interphase or early prophase.
 It occurs due to breakage and reunion of the chromosome
segments caused by radiations or chemicals.
 Structural changes causes changes in phenotype, fertility, viability
and karyotype of an individual.
 • Type of Structural Changes

• 1. Deletion or Deficiency:- It refers to loss of portion of

segment from a chromosome.
• Based on the locations of loss of genes, deletion are divided
into two types.
i. Terminal Deletion
ii. Interstitial Deletion
• (A). Terminal Deletion:- Loss of a portion from terminal end of
chromosome, known as Terminal deletion. It may be two
types, (a). Heterozygous (deficiency occurs in only one
chromosome of pair. (b). Homozygous (Deficiency occurs in
both chromosomes of a pair).
• (B).Interstitial Deletion:- Loss of intermediate portion of a
chromosome, or between telomere or centromere, is known as
Intercalary or interstitial deletion. The deleted portion comes
out and remaining segments reunited.
 • Effects of Deletion:-

 Small deletion (Heterozygous) is viable while large deletion

(homozygous) is lethal for individual.
 Crossing over is also suppressed in presence of deletion due to loss
of corresponding portion in homologous chrmosomes.
 Deletion also affect phenotype due to deletion in short arm of
chromosome which causes cri du chat (cry like cat) syndrome in
Man.
 Significance:- Deletion are important for creating variability by
chromosomal mutations and used as a cytological tool for gene
mapping.
• 2. Duplication:- It refers to the presence of a segment twice in
the same chrmosome. It is also known as repeat.
• It is four type:-
i. Tandem
ii. Reverse Tandem
iii. Displaced
iv. Reverse Displaced
i. Tandem:- In this type of duplication, duplicated segment is
present in the same sequence of genes by the original
segment of a chromosome.

ii. Reverse Tandem:- In this type of duplication, duplicated

segment is present in the reverse sequence of the genes by
the original segment of a chromosome
iii. Displaced:- In this type of duplication, duplicated segment is
present away from the original segment but on the same arm
of the chromosome.

iv. Reverse displaced:- In this type of duplication, duplicated

segment is present away from the original segment but on the
other arm of the chromosome.
 • Effects of Duplication

 Duplication increases the number of genes in the chromosome.

 Crossing over also suppressed due to duplication of the
corresponding segment of the chromosome.
 Charcot marie tooth disease.
 Significance:- Duplication do not reduce viability and are less
harmful than deletions. Duplication leads to addition of some
genes, which may have an important role in evolution.
3. Translocation:- It refers to the one way or reciprocal transfer
of the segement between non-homologous chromosomes.

• Translocation differs from the crossing over because it

involves non-homologous chromosomes while crossing over
involves non-sister chromatids of homologous chromosomes.
• Translocations are three types:-
i. Simple Translocation:- In this type of translocation, a
segment of a chromosome is transferred and attached to
the terminal end of a non-homologous chromosome
• Shifts:- In this type of translocation, a intermediate or
intercalary segment from one chromosome transfer to the
intercalary position of non-homologous chromosome, is
known as shift.
iii. Reciprocal Translocation:- In this type of translocation,
one break occurs in each chromosome and occurs
mutual exchange of segments between non-homologous
chromosomes, is known as Reciprocal Translocation.
These translocations are very common and have great
evolutionary significance.

• Sometimes more than two non-homologous

chromosomes are involve in translocation, which is
known as Multiple Translocation
• Robertsonian Translocation: Clinically more
important type of translocation is Robertsonian translocation. In this
disorder, the long arms of two nonhomologous chromosomes fuse at
the centromere, forming a single chromosome. Robertsonian
translocations are confined to chromosomes 13, 14, 15, 21, and 22
because the short arms of these chromosomes are very small and
contain no essential genetic material.
The short arms are usually lost during subsequent cell divisions. Because
the carriers of Robertsonian translocations lose no important genetic material, they
are unaffected although they have only 45 chromosomes in each cell. Their
offspring, however, may have serious monosomies or trisomies. For example, a
common Robertsonian translocation involves the fusion of the long arms of
chromosomes 21 and 14. An offspring who inherits a gamete carrying the fused
chromosome can receive an extra copy of the long arm of chromosome 21 and
develop Down syndrome. Robertsonian translocations are responsible for
approximately 3% to 5% of Down syndrome cases. Parents who carry a
Robertsonian translocation involving chromosome 21 have an increased risk for
producing multiple offspring with Down syndrom
 • Effects of Translocation:-
 Translocations lead to duplication and deletion of genes. Because,
gametes with duplication or deficiency are inviable.
 Crossing over is also suppressed in translocated chromosomes.
 Translocation change the size of chromosome and position of
centromere also.
 Translocation also affect phenotype e.g. Progeny of individual
heterozygote with a translocation involving chromosome number 21,
can arise as Downy Syndrome in Human.
 Significance:- Translocations alter the chromosome size,
chromosome number and karyotype and thus plays an important
role in formation of species.
4. Inversion:- It refers to the structural change in a chromosome
in which a segment is oriented in a reverse sequence.
Based on whether centromere is involved or not involved in
inversions, It is classified into two types:-
i. Paracentric Inversion
ii. Pericentric Inversion
i. Paracentric Inversion:- When the centromere isn’t involved in
inversion, is known Paracentric Inversion. In this type of
inversion breaks occurs only in one arm of chromosome.
ii. Pericentric Inversion:- When the centromere is involved in
the Inversion, is known Pericentric Inversion. In type of
inversion, breaks occurs both in each of the two arms of a
chromosome
 • Effects of Inversion
 The crossing over in the inversion leads to formation of
chromosomes with duplications and deficiency, which causes
individual inviable and leads to 50% sterility.
 Gene order is changed in the inverted segment of a
chromosome.
 Pericentric inversions changes the karyotype by shifting the
position of centromere.
 Significance:- Inversion also play an important role in the
evolution of new species by changing the karyotype of an
individual.
 Turner
Syndrome
Presented By maham jan
4TH Semester
INS-KMU Peshawar
 Outlines:

1. Introduction
2. Risk Factors
3. Pathophysiology
4. Clinical Manifestation
5. Diagnosis
6. Treatment
INTRODUCTION:
• Turner syndrome, also known as 45,X or monosomy X, is a genetic
disorder that affects females.
• It occurs when one of the X chromosomes is completely or partially
missing.
• Instead of the usual XX sex chromosome configuration, affected
individuals have only one X chromosome (45,X), or they may have a
mosaic pattern (45,X/46,XX), where some cells have the typical XX
configuration while others have the 45,X configuration.
Types Of Turner Syndrome
There are different types of Turner syndrome (TS) based on howone of the Xchromosomes is affected:

• Monosomy X: This type means each cell has only one X chromosome instead of two.
About 45% of people with TS have monosomy X. The chromosomal abnormality
happens randomly during the formation of reproductive cells (eggs or sperm) in
the affected person’s biological parent. If one of these atypical reproductive cells
contributes to the genetic makeup of a fetus during conception, the baby will have a
single X chromosome in each cell at birth.
• Mosaic Turner syndrome: This type makes up about 30% of TS cases. Some of your
child’s cells have a pair of X chromosomes, while other cells only have one. It
happens randomly during cell division early in pregnancy.
• Inherited Turner syndrome: In rare cases, babies may have inherited TS, meaning
their biological parent was born with it and passed it on. This type usually happens
because of a missing part of the X chromosome.
 RISKFACTORS:

Turner Syndrome is not typically inherited, and most cases occur sporadically.
However, there are a few risk factors and associations:
• Advanced Maternal Age: The risk of having a child with Turner Syndrome
appears to increase with maternal age, especially in women over 35.
• Previous Affected Child: If a woman has had a previous child with Turner
Syndrome, there may be a slightly increased risk in subsequent pregnancies.
• Non-Disjunction during Gametogenesis: Errors in the separation of
chromosomes during the formation of eggs or sperm can lead to
chromosomal abnormalities in the offspring.
Pathophysiology & Alterations of chromosomes:

1) Non-disjunction:
a. Non-disjunction is a common mechanism leading to Turner syndrome. It
occurs during cell division, either in the formation of eggs (oogenesis) or
sperm (spermatogenesis), resulting in an unequal distribution of
chromosomes.

b. If non-disjunction occurs during oogenesis, and the egg lacks an X

chromosome, it will combine with a normal X-carrying sperm during
fertilization, leading to monosomy X.
2. X Chromosome Deletion:
• In some cases, part of the X chromosome may be missing or
deleted. This can occur randomly during the formation of egg or
sperm cells.

• The specific genes located on the missing portion of the X

chromosome can influence the severity of clinical features.
3. Ring Chromosomes:
• In some cases, a broken piece of the X chromosome may form
a ring structure. This is known as a ring X chromosome.

• The formation of a ring chromosome can result in gene

disruption and functional consequences. The specific genes
affected by the ring chromosome can influence the severity of
clinical manifestations.
4. Mosaicism:
• Mosaicism in Turner syndrome refers to the presence of two or
more cell lines with different chromosomal compositions within the
same individual.

• Chromosomal breakage and rearrangements during early cell

divisions can lead to the formation of mosaic patterns. For example,
an individual may have a mixture of cells with a 45,X configuration
and cells with a normal 46,XX configuration.
 Clinical Manifestations:
• Gonadal Dysgenesis:
• Individuals with Turner syndrome typically have streak gonads,
which are underdeveloped ovaries that lack functioning ovarian
tissue.
• This results in decreased production of sex hormones, particularly
estrogen. As a consequence, there is an absence of pubertal
development or incomplete pubertal development.
 4. Physical Features: Some physical features commonly
seen in Turner syndrome include a webbed neck, low
hairline at the back of the neck, low-set ears, and a broad
chest with widely spaced nipples. Swelling of the hands
. and feet due to lymphedema may also be present in
infancy.
5. Cardiovascular Anomalies: Individuals with Turner
syndrome have an increased risk of congenital heart
defects, particularly coarctation of the aorta and bicuspid
aortic valve. These conditions can lead to hypertension
and are important causes of morbidity and mortality in
affected individuals.
7. Renal Abnormalities: Kidney malformations,
such as horseshoe kidney or renal agenesis,
may be present in some individuals with Turner
syndrome. These anomalies can sometimes lead
to urinary tract infections or other renal
complications.

8. Other Features: Additional features may

include hearing loss, thyroid dysfunction,
diabetes mellitus, and autoimmune disorders
such as hypothyroidism and celiac disease.
 Diagnosis:
Diagnosing Turner Syndrome involves a combination of
clinical evaluation, genetic testing, and imaging studies. The
diagnosis may occur prenatally, in infancy, or during
childhood.

• Prenatal Diagnosis:
– Turner Syndrome may be suspected based on abnormal
findings in routine prenatal ultrasound, such as fetal hydrops or
cardiac anomalies.
– Chromosomal analysis through chorionic villus sampling (CVS)
or amniocentesis can confirm the diagnosis.
 Diagnosis:
• Postnatal Diagnosis:
– Clinical signs and symptoms, such as short stature, webbed neck, and lack of
secondary sexual characteristics, may prompt further investigation.
– Karyotype analysis, which involves examining the number and structure of
chromosomes, is the gold standard for confirming Turner Syndrome. Blood is
drawn, and cells are cultured for chromosomal analysis.

• Imaging Studies:
– Echocardiography is often performed to assess cardiac structure and
function, given the increased risk of cardiovascular anomalies.
– Renal ultrasound may be done to evaluate the kidneys for structural
abnormalities.
Diagnosis:
• Genetic Testing:
– Fluorescence in situ hybridization (FISH) or chromosomal
microarray analysis (CMA) may be used to detect specific
chromosomal abnormalities in addition to standard karyotyping.

• Hormonal Testing:
– Hormonal assessments, including measuring levels of
gonadotropins and sex hormones, can provide information about
ovarian function and guide hormone replacement therapy.
References:
1. National Liberary of Medicine
2.Nation Center of Biotechnology
3.Understanding Pathophysiology
4.Fundamental Pathology
Thank you!
Klinefelter’s
Syndrome
Presented by
Munir Khan &
Ishrat Perveen
4TH Semester
INS-KMU Peshawar
 Objectives
What is Kleinfelter’s Syndrome.
The Pathophysiology and the clinical
manifestation of Kleinfelter’s Syndrome.
Structural Abnormalities during Kleinfelter’s
Syndrome.
Factors causing chromosomal breakage.
Diagnoses test for Klinefelter Syndrome.
Treatments of Klinefelter’s Syndrome.
 What is Klinefelter’s Syndrome?
 Klinefelter 's syndrome is a genetic disorder that
only affects males.
It occurs when a boy is born with one or more
extra X chromosomes (XXY) instead of usual
(XY) , which causes a boy to produce less
testosterone than a normal boy.

 Due to having an extra X chromosome, the male

may possibly have some physical traits
unusual for males.
 What is Klinefelter’s Syndrome?
Instead of an XY sex chromosome
pattern that most males have, these males
have an XXY pattern.
Some people with Kleinfelter’s consider
themselves to be transgender,
intersexed, or transsexual, due to
having a more feminine appearance and/or
feminine emotions.
 History of Klinefelter’s Syndrome:
 In 1942, Klinefelter’s was discovered by Dr. Harry
Klinefelter's, along with other doctors at General
Hospital in Boston.

 Doctors reported a group of males with “enlarged

breasts, sparse facial and body hair, small testes,
and inability to produce sperm.”

 By the late 1950’s, researches discovered that these

men had an extra sex chromosome thus having
the pattern XXY.
 Other Names for Klinefelter’s:
47, XXY
XXY Syndrome
XXY Trisomy
Or 3+X Chromosomes with Y

 Approximately 1 in 500 to 1,000.

 Causes:
Mechanism for retaining the extra X
chromosome is through a nondisjunction
event during meiosis II in the female.

Nondisjunction will occur when sister

chromatides on the sex chromosome, in
this case an X and an X, fail to separate.
(meiosis) an XX egg is produced which ,
when fertilized with a Y sperm, yields XXY
offspring.
Sister Chromatide
 Pathophysiology:
The normal male has one X and one Y
chromosome (XY). In KS, there is an extra X
chromosome (XXY).
The presence of the extra X chromosome leads
to disruptions in the development of the testes
during fetal development.
This affects the production of testosterone, the
male sex hormone.
 Clinical Manifestations:
• Infertility:
 Most individuals with KS are infertile due to
underdeveloped testes, leading to reduced
sperm production.
• Hormonal Imbalances:
 Low testosterone levels can lead to
delayed or incomplete puberty.
 This may result in less facial and body
hair, reduced muscle mass, and a higher
voice pitch.
 Clinical Manifestations:
• Physical Characteristics:
 Taller stature than average.
 Longer limbs.
 Gynecomastia (enlarged breast tissue).
• Language Symptoms:
 Learn to talk late.
 Problems reading.
 Trouble processing what they hear.
 Structural Abnormalities:
• Underdeveloped Testes:
Testes are smaller and function less
effectively.
• Penis Size:
Slightly smaller than average due to
hormonal imbalances.
• Gynecomastia:
Enlarged breast tissue caused by hormonal
imbalances.
 Structural Abnormalities:
• Body Composition:
Higher body fat and reduced muscle mass.
• Taller Stature:
Individuals with KS are generally taller with
longer limbs.
• Facial and Body Hair:
Less development of facial and body hair.
Factors Causing Chromosomal Breakage:
• Random Occurrence:
The extra X chromosome (XXY) in Klinefelter
Syndrome is often a random event during cell
division. Can Not predict the exact Cause.
• Cell Division Glitch:
Sometimes, when cells are dividing, a mistake
happens, leading to the presence of an extra X
chromosome.
• Advanced Maternal Age:
There is a slight increase in the risk of Klinefelter
Syndrome when mothers are of advanced age
during pregnancy.
Diagnoses test for Klinefelter syndrome:
 Hormone testing: Blood or urine samples can
reveal abnormal hormone levels that are a
sign of Klinefelter syndrome.
 Chromosome analysis: Also called
karyotype analysis, this test is used to
confirm a diagnosis of Klinefelter syndrome. A
blood sample is sent to the lab to check the
shape and number of chromosomes.
 Treatments of Klinefelter’s
Syndrome:
 Males with Klinefelter’s Syndrome can be
given testosterone therapy.

 If given around the age of puberty, it can

help a boy have normal body development.

 A infertility specialist may be able to help a

male with Klinefelter’s syndrome to get
a woman pregnant.
 Treatment of Klinefelter’s
Syndrome:
In males with enlarged breasts, a plastic
surgeon can remove excess breast tissue to
create a more typical-looking chest.

Some boys with Klinefelter syndrome may

face challenges in learning and socializing.
Discuss potential support with your child's
teacher, school counselor, or nurse for
assistance.
 Disorders of Adrenal Gland

Hammad
Nursing lecturer
KMU-INS

3/24/2024
 Adrenal Gland

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Anatomy
 Adrenal glands are composed of two sections. The
interior (medulla) produces adrenaline-like hormones.
The outer layer (cortex) produces a group of hormones
called corticosteroids. Corticosteroids include:
 Glucocorticoids. These hormones, which include
cortisol, influence body's ability to convert food into
energy, play a role in your immune system's
inflammatory response and help your body respond to
stress.

3/24/2024
CONTI..
 Mineralocorticoids. These hormones, which include
aldosterone, maintain your body's balance of sodium
and potassium to keep your blood pressure normal.
 Androgens. These male sex hormones are produced
in small amounts by the adrenal glands in both men
and women. They cause sexual development in men,
and influence muscle mass, sex drive (libido) and a
sense of well-being in both men and women.

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 Slide 3 of 26

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 Glucocorticoids
 Cortisol ( Hydrocortisone)----essential for life
 10-20 mg/day
 Controlled primarily by ACTH adrenocorticotropic hormone
 Marked circadian rhythm in non-stressful condition.
 Highest levels b/w 4 a.m. & 8 a.m.
lowest b/w midnight & 3 a.m.
If sleeping pattern changes it takes several days for
adjustment of the ACTH / cortisol secretion to take place e.g.
day to night shift

3/24/2024
Cortisol
 Is a lipid soluble hormone called glucocorticoid it is not soluble in
water that why it needs protein carrier (globulin).
 All cortisol are bound except 5 %. This free cortisol is biologically
active.
 Its function is maintain circadian rhythm

 Cortisol can help control blood sugar level,regulate metabolism, help

reduce inflammation and controlling effect on salt and water balance
and help to control blood pressure.

 During stress the body needs energy, so cortisol increases

gluconeogenesis ( synthesis of new glucose molecules) means increase
proteolysis and lipolysis.

3/24/2024
 conti..
 Cortisol also maintain blood pressure by increase
sensitivity peripheral blood vessels to
chetacholamines such as adrenaline and nor
adrenaline which narrow blood vessel lumen.
 Cortisol decreases immune response by decreasing
prostaglandin and interleukin as well as it also
inhibit proliferation of T lymphocytes.
 Its receptors in the brain which influence in mood
and memory.

3/24/2024
Cushing’s Syndrome:
 “According to National Institute of health (1999),
Cushing’s syndrome, also called hypercortisolism, is
rare endocrine disorder, characterized by a variety of
symptoms and physical abnormalities.
 It may be caused by either, prolonged exposure of the
body’s tissue to high levels of Cortisol or by the over
production of cortisol in the body.

3/24/2024
International Data:
 10 people per million population, annually
 Affects women 5 times more than men
 1 in 5000 hospital admission
 70% reported cases are diagnosed as pituitary adenomas
 Occurs most frequently during the age twenties and fifties
 15-30% cases are of endogenous Cushing’s Syndrome
 Adenomas and Carcinomas are about equally common in
adults and children
 Carcinomas are predominant

3/24/2024
3/24/2024
 The most common symptom of Cushing's syndrome is sudden
weight gain, usually manifested by central obesity.

3/24/2024
Pathophysiology
 Loss of normal circadian rhythmicity of ACTH and
cortisol secretion.
 Absence of normal regulatory negative feedback of
corticosteroids on the pituitary gland and
hypothalamus.
 Negative feedback does exist, but the set point for
ACTH suppression is much higher than normal.

3/24/2024
 Conti..
 High level of cortisol leads to elevate blood glucose
level resulting in increase insulin level which targets
adipocytes in the center of the body especially around
the buttocks. Through this mechanism an enzyme
lipoprotein lipase is activated which helps in
accumulation of fat molecule in adipose cells.
 High cortisol level may also cause hypertension for two
reasons, one by amplifying with chetocilamines and
other by cross reacting with mineralocorticoid
receptors. Which increases blood pressure by
retaining fluid.

3/24/2024
Conti..
 High cortisol level also inhibit gonadotropin hormone
from the hypothalamus, this leads to missing up
ovarian and testicular function.
 It also impairs brain function

3/24/2024
 Manifestation
 Truncal obesity, round or  irritability and anxiety
moon face & buffalo hump,  excessive hair growth in
weight gain
females
 Stretch marks, or striae
 Bruising (easy)
 Skin deeply pigmented
 Thin, vulnerable skin
 Hypernateremia,hypokalemia,
metabolic alkalosis  Muscular weakness

 Raised blood pressure  Fatigue

 Blurred vision

3/24/2024
Conti..
 Irregular or stopped  Slow healing of cuts,
menstrual cycles in insect bites and
females infections
 Reduced sex drive and  Type 2 DM
fertility in males  Psychological changes
 Facial flushing  Impaired wound
healing
 Osteoporosis, bone
fracture
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3/24/2024
 Typical abdominal Striae

3/24/2024
Hypocortical Functioning

 Some times partial dysfunction of the adrenal

cortex.
 Glucocorticoid secretion
 Mineralocorticoid secretion
 Primary adrenal insufficiency is termed Addison’s
disease

3/24/2024
Addison's disease
 an underactive adrenal gland
 An underactive adrenal gland produces insufficient
amounts of cortisol.
( Hypocortisolism).

 Adrenal insufficiency was first identified by Dr.

Thomas Addison in 1849.

3/24/2024
Incidence of Addison’s Disease
 Reported incidence of Addison disease in US is 5 or 6
cases per 1,000,000 population per year, with a
prevalence of 60-110 cases per 1, 000,000 population.

 Sex: The male to female ratio is 1:1.5-3.5.

 Age: Addison disease can occur in persons of any age;

most common in people aged 30-50 years.

3/24/2024
Addison’s Disease.

 “Addison’s disease is characterized by elevated

serum ACTH level with inadequate corticosteroids
synthesis and secretion.”

 Adrenal insufficiency occurs when at least 90

percent of the adrenal cortex has been destroyed.

 Hypo function of the adrenal cortex may affect

glucocorticoid or mineralocorticoid secretion or a
combination of both.

3/24/2024
 Causes

 Idiopathic

 Primary & Secondary Adrenal Insufficiency.

 Auto-immune disease.

 Primary adrenal insufficiency or Addison's disease may

be due to the destruction of the adrenal gland cortex.

3/24/2024
 Causes conti..
 Hypocortisolism develops because of:

Inadequate stimulation of the adrenal glands by

ACTH
Use of corticosteroids as a treatment (such as
prednisone) may cause a slow down in production
of natural corticosteroids by the adrenal glands.
 Familial adrenal insufficiency
 Cancer, adrenal hemorrhage and other infections.
(T.B.)

3/24/2024
 AD with Pituitary ACTH insufficiency
Cortisol producing endocrine tumor
surgical removal of benign, or noncancerous, ACTH-
producing tumors of the pituitary gland
Exogenous administration of corticoids

Suppress ACTH production through normal feedback

mechanism

Low to absent ACTH levels

Inadequate adrenal stimulation

Adrenal cortex atrophy

Decreased corticosteroidgenesis
3/24/2024
 Pathophysiology

 Elevated serum ACTH levels

 Inadequate corticosteroid synthesis and output.
 More than 90 % of total adrenocortical tissue must be
destroyed.

3/24/2024
Conti..
 Insufficiency of all hormone, produced by renal
cortex.
 Chorticotropic releasing hormone from hypothalamus
stimulates cells in anterioprpitutary to secrete ACTH
hormone which further stimulates renal cortex as
result three hormones will be released
 Minrochorticoid (aldosterone)
 Glucocorticoids (cortisol)
 Androgen (male and female)

3/24/2024
Symptoms of Addison's Disease
 weakness  weight loss
 fatigue  dehydration
 dizziness  loss of appetite
 rapid pulse  intense salt craving
 dark skin (first noted  muscle aches
on hands and face)  nausea
Hyperpigmentation  vomiting
seen in 98% of people
 diarrhea
black freckles
 intolerance to cold
3/24/2024
 Aldosterone Deficiency
 Hyponatremia/hypercalemia
 Hypotension
 Tachycardia & decrease C.O
 High renin levels with low aldosterone.
 Dehydration, irritability and depression
 If loss of Na & water is severe, CVS collapse
Androgen Deficiency
 In women, causes loss of axillary's and pubic hair and
decrease hair over the extremities.

3/24/2024
3/24/2024
 THANK YOU

3/24/2024
Disorders of Growth Hormone
Objectives
 At the end of this presentation the students will be
able to:
 Define growth hormone.
 Discuss functions of growth hormone.
 Describes disorders of growth hormone:
o Gigantism
o Acromegaly

o Dwarfism
Growth hormone
 Growth hormone (GH) is a peptide hormone that
stimulates growth, cell reproduction and regeneration
in humans and other animals.
 Growth hormone is a 191-amino acid, single-chain
polypeptide that is synthesized, stored, and secreted
by somatotropic cells within the lateral wings of the
anterior pituitary gland.
 Somatotropin (STH) refers to the growth hormone
produced naturally in animals, whereas the term
somatropin refers to growth hormone produced by
recombinant DNA technology.
Function of growth hormone
 Effects of growth hormone on the tissues of the body
can generally be described as anabolic (building up).
Like most other protein hormones, GH acts by
interacting with a specific receptor on the surface of
cells.
 Increased height during childhood is the most widely
known effect of GH.
o In addition to increasing height in children and
adolescents, growth hormone has many other effects
on the body:
 Increases calcium retention, and strengthens and
increases the mineralization of bone.
Cont….
 Increases muscle mass through sarcomere hyperplasia
 Promotes lipolysis
 Increases protein synthesis
 Stimulates the growth of all internal organs excluding
the brain.
 Plays a role in homeostasis
 Reduces liver uptake of glucose
 Promotes gluconeogenesis in the liver
 Contributes to the maintenance and function of
pancreatic islets.
 Stimulates the immune system.
Disorders of growth hormone
 Following are the disorders of growth hormone:

Gigantism

Acromegaly

Dwarfism
Gigantism
 Gigantism is a condition characterized by
excessive growth and height significantly above
average.
 In humans, this condition is caused by over-
production of growth hormone in childhood
before the long bone epiphyses closes resulting in
persons between 7 feet and 9 feet in height.
Etiology
 Gigantism is usually caused by a tumor on the
pituitary gland of the brain. It causes growth of the
hands, face, and feet.
 In some cases the condition can be passed on
genetically through a mutated gene.
Pathophysiology
 Gigantism is caused by an excess secretion of growth
hormone before the fusion of the epiphyseal plates.
 GH is under the control of GHRH (which promotes
GH) and somatostatin (which inhibits GH). GH in turn
increases levels of IGF-1 (insulin-like growth factor-1).
 IGF-1 is produced by hepatocytes in the Liver and is the
main mediator of growth processes in the body, IGF-1
promotes protein synthesis, skeletal growth, and cell
proliferation.
 Hence, it is IGF-1 that is actually implicated in this
disease. A high IGF-1 level is the common factor seen in
all cases of gigantism.
Symptoms
• The child will grow in height, as well as in the
muscles and organs. This excessive growth makes
the child extremely large for his or her age.
Other symptoms include:
• Delayed puberty
• Double vision or difficulty with side (peripheral)
vision
• Frontal bossing and a prominent jaw
• Headache
Cont….
 Increased sweating
 Irregular periods (menstruation)
 Large hands and feet with thick fingers and toes
 Thickening of the facial features
 Weakness.
Acromegaly
 Acromegaly ( from two Greek word akros "extreme"
or "extremities" and megalos "large") is a syndrome
that results when the anterior pituitary gland produces
excess growth hormone (GH) after epiphyseal plate
closure at puberty.
 A number of disorders may increase the pituitary's GH
output, although most commonly it involves a GH-
producing tumor called pituitary adenoma, derived
from a distinct type of cell (somatotrophs).
Etiology
 Acromegaly occurs in about 6 of every 100,000 adults.
It is caused by abnormal production of growth
hormone after the skeleton and other organs finish
growing.
 The cause of the increased growth hormone release is
usually a noncancerous (benign) tumor of the
pituitary gland.
 The pituitary gland, which is located just below the
brain, controls the production and release of several
different hormones, including growth hormone.
Pathophysiology
 Acromegaly is characterized by hypersecretion of
growth hormone (GH), which is caused by the
existence of a secreting pituitary tumor in more than
95% of acromegaly cases. Pituitary tumors are
benign adenomas.
 In rare instances, elevated GH levels are caused by
extra pituitary disorders. In either situation,
hypersecretion of GH in turn causes subsequent
hepatic stimulation of insulin-like growth factor-1
(IGF-1).
Symptoms
 Weakness
 Fatigue
 Excessive height
 Excessive sweating
 Headache
 Hoarseness
 Joint pain
 Large bones of the face
 Large feet and large hands
Cont….
 Large jaw (prognathism) and tongue (macroglossia).
 Limited joint movement
 Sleep apnea
 Swelling of the bony areas around a joint
 Excess hair growth in females
 Weight gain (unintentional)
 Dwarfism
 Dwarfism occurs when an individual is short in
stature resulting from a medical condition caused by
problems that arise in the pituitary gland in which the
growth of the individual is very slowed or delayed.
 Dwarfism is generally defined as an adult height of 4
feet 10 inches or less (147 centimeters). The average
adult height among people with dwarfism is 4 feet (122
cm).
Etiology
Following are the main causes of dwarfism.

• Achondroplasia.

• Turner syndrome.

• Growth hormone deficiency.

Signs and symptoms
 An average-size trunk
 Short arms and legs, with particularly short upper arms and
upper legs
 Short fingers, often with a wide separation between the
middle and ring fingers
 Limited mobility at the elbows
 A disproportionately large head, with a prominent
forehead and a flattened bridge of the nose
 Progressive development of bowed legs (genu varum)
 Progressive development of swayed lower back (lordosis)
 An adult height around 4 feet — about 122 cm
References
 Melmed S, Kleinberg D. Pituitary masses and tumors. In:
Kronenberg HM, Melmed S, Polonsky KS, Larsen PR.
Williams Textbook of Endocrinology. 12th ed. Philadelphia,
PA: Saunders Elsevier; 2011:chap 9.
 Daniels ME (1992). "Lilly's Humatrope Experience". Nature
Biotechnology 10 (7): 812.
 Powers M (2005). "Performance-Enhancing Drugs". In
Deidre Leaver-Dunn; Joel Houglum; Harrelson, Gary L..
Principles of Pharmacology for Athletic Trainers. Slack
Incorporated. pp. 331–332.
Disorder of Endocrine Pancreas Diabetes Mellitus
Hammad
Nursing Lecturer
KMU INS
Objectives
 By the end of the class student will be able to,
 Review of Anatomy & Physiology of endocrine pancreas.
 Briefly discuss the classification of diabetes mellitus (DM)
 Discuss etiology, pathophysiology, and clinical manifestations
of Type 1 DM & Type 2 DM.
 Identify pathogenesis and manifestations of the acute and
chronic complications of diabetes mellitus.
 Pancreas
 The pancreas is a long, slender organ, most of which is located
posterior to the bottom half of the stomach. Although it is primarily
an exocrine gland, secreting a variety of digestive enzymes,
Functioning as an exocrine gland, the pancreas excretes
enzymes to break down the proteins, lipids, carbohydrates, and
nucleic acids in food. Functioning as an endocrine gland,
the pancreas secretes the hormones insulin and glucagon to
control blood sugar levels throughout the day.

 Its pancreatic islets —clusters of cells formerly known as the islets

of Langerhans—secrete the hormones glucagon from the center of
alpha cells, insulin from the periphery of beta cells, somatostatin, and
pancreatic polypeptide (PP).
 Physiology
 The alpha cell produces the hormone glucagon and makes up
approximately 20 percent of each islet. Glucagon plays an
important role in blood glucose regulation; low blood glucose
levels stimulate its release.

 The beta cell produces the hormone insulin and makes up

approximately 75 percent of each islet. Elevated blood glucose
levels stimulate the release of insulin.
 Conti…
 The delta cell accounts for four percent of the islet cells and
secretes the peptide hormone somatostatin. Recall that
somatostatin is also released by the hypothalamus (as
GHIH).

 The stomach and intestines also secrete it. An inhibiting

hormone, pancreatic somatostatin inhibits the release of both
glucagon and insulin.

 The PP cell accounts for about one percent of islet cells and
secretes the pancreatic polypeptide hormone.
 CONTI..
 It is thought to play a role in appetite, as well as in the
regulation of pancreatic exocrine and endocrine secretions.

 Pancreatic polypeptide released following a meal may reduce

further food consumption; however, it is also released in
response to fasting.
 Diabetes Mellitus
 Diabetes Mellitus (sugar diabetes) is a disease characterized by
high levels of sugar (glucose) in the blood.

 The disease was given its name because of the glucose

excretion in the urine.

(The term "diabetes" mellitus (honey sweet) was added by

Thomas Willis (Britain) in 1675 after rediscovering the sweetness of
urine and blood of patients).

 It is endocrine and metabolic disorder.

Diabetes Mellitus

The disease can be

classified into several
types, depending on its
cause.
 Cause
 Diabetes mellitus is caused by an absolute or relative lack of
insulin that, among other consequences, leads to an increase in
plasma glucose concentration.
TYPE-I (Insulin-Dependent
Diabetes Mellitus)

(IDDM)
 IDDM or Type-I DM
 In type I (insulin-dependent diabetes mellitus [IDDM],
previously called juvenile diabetes; there is an absolute lack of
insulin, so that the patient needs an external supply of insulin.

 The condition is caused by a lesion in the beta cells of the

pancreas, as a rule produced by an autoimmune mechanism
that may, in certain circumstances, have been triggered by a
viral infection.
 Pathophysiology of type 1 DM
 Type 1 diabetic mellitus is due to type IV hypersensitivity
response (cell mediated response) where persons own T
cells attack pancreas. Normally T cells react against
antigen which prevent to attack other body organs, is
called T cell self tolerance.
 In DM because of triggering factor lose of self tolerance
of T cells occur. And T cells specifically target beta cells
of pancreas. T cells coordinate other cells (autoantibodies)
and target beta antigen cells and destroy them, resulting
in less insulin and glucose pile up in blood and can not go
into the cell.
 After the death of the beta cells, the autoantibodies again
disappear.
 Pathophysiology of type 1 DM
 One gene in chromosome number 7, human leukocyte antigen
(HLA) is important for regulation of immune response. This
gene is encode for Major histocompatibility complex(MHA)
which is important for recognizing foreign molecule and
maintain self tolerance.
 MHC is serving palate, where antigen are present for immune
response.
 90 % cells destroy until symptoms appear.
Four major symptoms of type 1
DM
 Polyphagia
 Glycosuria
 Polyuria
 Polydipsia.
 Due to high blood glucose level in blood, adipose tissues and
muscles cells start breaking down fats (lipolysis) and proteins
(proteolysis) due to which weight lose occur and increase
feeling hungry called (polyphagia).
 Conti..
 Since glucose is osmotically active which leads to increase
circulation toward kidney this further leads to polyuria,
dehydration and polydipsia.
 Complications of type 1 DM
 Diabetic keto acidosis: During the process of lipolysis, liver
starts to make ketone bodies (acetic acid and beta
hydroxybeuteric acid) this condition is called diabetic
ketoacidosis. These ketone bodies are important because they
can be used by cell as a.
 Increase acidity of blood further cause three critical symptoms.
1. Kussmule respiration
2. Hyperkalemia
3. High anion gape.
 Conti..
 Cells also contain transporter that exchange H ion.when the
blood gets acidic, means there is high level of hydrogen ions
resulting in H ions getting into the cell and potassium getting
out of the cell. This leads to hyperkalemia.
 Insulin also stimulates Na, K ATPase which help K in and Na
out of the cells, when there is no insulin K stays outside of cells
and cause hyperkalemia.
Type II (non-insulin-dependent
diabetes mellitus)

(NIDDM)
 Type-II DM or NIDDM
 Type II (non-insulin-dependent diabetes mellitus [NIDDM],
formerly called maturity onset diabetes; is by far the most
common form of diabetes. Here, too, genetic disposition is
important.
 However, there is a relative insulin deficiency: The patients are
not necessarily dependent on an exogenous supply of insulin.
 Insulin release can be normal or even increased, but the target
organs have a diminished sensitivity to insulin.
 Type-II DM or NIDDM
 Most of the patients with type II diabetes are overweight. The
obesity is the result of a genetic disposition, too large an intake
of food, and too little physical activity.
 The imbalance between energy supply and expenditure
increases the concentration of fatty acids in the blood.
 This in turn reduces glucose utilization in muscle and fatty
tissues. The result is a resistance to insulin, forcing an increase
of insulin release.
 Pathophysiology of type 2 DM
 Obesity, HTN, and lack of exercise.
 For example excess fats in adipose tissues cause release of free
fatty acid adipokine which are signaling molecule for
inflammation.
 In type 2 diabetic mellitus the body produces more insulin
resulting in hyperplasia (grow in number) and hypertrophy
(grow in size) of beta cells occur. But this works for a while.
 Along with insulin the beta cells also secretes Amylin over
time which build in islet.
 Conti..
 Beta cells become axuasted, die and shrink by compensation
called hypotropy.Then after it leads to hyperglycemia and
cause symptoms of type 1 DM.
 In type 2 DM, DKA is very uncommon, because there is still
some circulating insulin for which beta cells try to compensate
for insulin to regulate Na K pump.
Complications of type 2 DM
 Hyperosmolar Hyperglycemia: The condition in which
plasma osmolarity gets increase and it leads to dehydration.
 Glucose act as a solute so the glucose level in the blood is high
which cause water come into the blood and cells become shrink
which leads to increase urination and dehydration.
 Sign and symptoms
 In acute insulin deficiency the absence of its effect on glucose
metabolism results in hyperglycemia. The extracellular
accumulation of glucose leads to hyperosmolarity which father
leads polyuria,polyphasia, polydipsia, and glycosuria.

 The transport maximum of glucose is exceeded in the kidney

so that glucose is excreted in the urine . This results in an
osmotic diuresis with renal loss of water (polyuria), Na+, and
K+, dehydration, and thirst, dry mouth.
Other Symptoms

 Muscular weakness.
 Hyperlipidemia.
 Kussmaul breathing.
 weight loss.
Differences between type-1 and type-2 Diabetes Mellitus
 Type 1  Type 2
 Young age  Middle aged, elderly
 Normal BMI, not obese  Usually overweight/obese
 No immediate family history  Family history usual
 Short duration of symptoms  Symptoms may be present for
(weeks) months/years
 Can present with diabetic  Do not present with diabetic
coma (diabetic ketoacidosis) coma
 Insulin required  Insulin not necessarily
required
 Previous diabetes in pregnancy

These differences are not absolute

Gestational diabetes
 A form of glucose intolerance that is diagnosed in some
women during pregnancy.
 During pregnancy, gestational diabetes requires treatment to
normalize maternal blood glucose levels to avoid
complications in the infant.
 It is common in third trimester. Hormone interferes with
insulin action on insulin receptors.
Conti..
 After pregnancy, 5% to 10% of women with gestational
diabetes are found to have type 2 diabetes.
 Women who have had gestational diabetes have a 20% to 50%
chance of developing diabetes in the next 5-10 years
Values of Diagnosis of Diabetes Mellitus

1mmol=18mg
 Management of DM
 The major components of the treatment of diabetes are:

A • Diet and Exercise

• Oral hypoglycaemic
B therapy

C • Insulin Therapy
Treatment and control
 Medications
 (insulin vs. hypoglycemic agents)
 Increase physical activity
 at least walk for 30 min. most days
 Appropriate diet
 vegetables
 fruit
 low in fat and carbohydrates
 Lifestyle changes
Acute complications of DM
 Diabetic ketoacidosis
 Hyperglycemia hyperosmolar state
 Hypoglycemia
 Diabetic coma
 Chronic complications
 Diabetic cardiomyopathy, damage to the heart, leading to
diastolic dysfunction and eventually heart failure.
 Diabetic nephropathy, damage to the kidney which can lead
to chronic renal failure, eventually requiring dialysis..
 Diabetic neuropathy, abnormal and decreased sensation,
usually in a 'glove and stocking' distribution starting with the
feet but potentially in other nerves, later often fingers and
hands. When combined with damaged blood vessels this can
lead to diabetic foot.
Conti….
 Diabetic retinopathy, growth of friable and poor-quality new
blood vessels in the retina as well as macular edema (swelling
of the macula), which can lead to severe vision loss or
blindness.
 Macrovascular disease leads to cardiovascular disease, to
which accelerated atherosclerosis is a contributor:
 Coronary artery disease, leading to angina or myocardial
infarction ("heart attack")
 Diabetic myonecrosis ('muscle wasting')
 Stroke (mainly the ischemic type)
 References
 American diabetic association.
Thyroid and Parathyroid Gland
Disorders
Hammad
Nursing Lecturer
KMU INS
 OBJECTIVES
By the end of class student will be able to
 Discuss anatomy and physiology of thyroid and para
thyroid gland and hypothalamic pituitary feed back
system.
 Discuss the disorders associated with thyroid gland
 Discuss the mechanism of action of para thyroid
hormone calcitonin.
 Explain the effect of hyperthyroidism and
hypothyroidism.
Anatomy
 The thyroid and parathyroid glands are situated
close to each other in the front of the neck.
 The thyroid gland produces the hormone thyroxin
(T4) and its more active form, T3, which act on
body cells to regulate metabolism (the chemical
reactions continually occurring in the body).
 T3 is an active hormone which is produced in by
T4 in the liver. That’s why only in liver failure T3
test can be done.
Conti..
 TSH bind with thyroid epithelial cell and form T4.T4
hormone release from colloid cells .
 Thyroglobulin, precursor T4 and T3 produced by
thyroid follicular cells through reaction with enzyme
thyroperoxidase.
 In the membrane of cell contain iodine pump.iodin
enters in the cells via sodium potassium pump and
bind with tyrosine residues in thyroglobulin.
monoiodotyrosine and diiodotyrosin combine to form
T3 and two molecules diiodotyrosin combine to form
T4.
 T4 hormone is lipid soluble hormone and need
protein carrier for example albumen.
Function of thyroid hormone
 ↑Na k pump to produce energy for skeleton
muscles, kidney, heart, and liver which are big
energy users in the body.
 ↑ BMR (rate of chemical reaction)
 ↑ oxygen and glucose
 Help in digestion of food
 Stimulate central nervous system which response
for alertness, reflexes and increase temperature.
 Regenerate new cells.
Conti…
 Some thyroid cells secrete the hormone calcitonin,
which lowers calcium in the blood.
 The parathyroid glands produce parathyroid
hormone (PTH), the main regulator of calcium.
Hypothyroidism
Hypo secretion of Thyroid Hormones:

 Thyroid hypo secretion occurs due to defects in :

 The thyroid gland itself.
 The hypothalamus or pituitary, resulting in a
deficiency in TSH production.
 Due to a slower metabolic rate and reduced heat
production, hypothyroid individuals cannot
tolerate cold temperatures.
Physiology
 The primary function of the thyroid is production of the
hormones T3, T4 and calcitonin. Up to 80% of the T4 is
converted to T3 by organs such as
the liver, kidney and spleen. T3 is several times more
powerful than T4.
 Feed Back
 The production of thyroxine and tri-iodothyronine is
regulated by thyroid-stimulating hormone (TSH),
released by the anterior pituitary.
 The thyroid and thyrotropes form a negative feedback loop:
TSH production is suppressed when the T4 levels are high..
 The TSH production itself is modulated by thyrotropin-
releasing hormone (TRH), which is produced by
the hypothalamus and secreted at an increased rate in
situations such as cold exposure (to stimulate
thermogenesis).
Pathophysiology of hypothyroidism
 Can be Primary or acquired.
 Immunoglobulin bind with receptors in epithelial cells
and destroy the receptors (thyroproxidase antibody),
cause entire gland destroy, inflamed, and atrophy
called hushimatose thyroiditis.
Conti..
Goitre (non toxic)
 It is a swelling of the neck or larynx resulting from
enlargement of the thyroid gland (thyromegaly),
associated with a thyroid gland that is not functioning
properly.
 Worldwide, over 90.54% cases of goitre are caused
by iodine deficiency.
 Sign and symptom
 Weight gain despite
 Poor appetite and cold intolerance.
 Constipation
 Lethargy.
 However, these symptoms are often nonspecific and hard
to diagnose
 Goitre
Pathophysiology
Pituitary gland (TRH/TIH)--Hypothalamus
(TSH)--Thyroid glands(receptors)-- thyroid
hormones (T3 AND T4) which are synthesised by
iodination of tyrosine-- iodine moves from plasma
to thyroid cell through Na and Iodide Spotters this
mechanism is controlled by TSH hormone.
Conti..
 Due to iodine deficiency hyperplasia of thyroid to
compensate for decreased efficacy.
 This regulation would disturbed by primary and
secondary cause.
 In primary cause the problem is with thyroid gland it
self and in secondary cause the problem is with
hypothalamus and pituitary gland.
 Cretinism
 It is a condition of severely stunted physical and
mental growth due to
untreated congenital deficiency of thyroid hormones
(congenital hypothyroidism) . It is most common
neonatal endocrine disorder.

 Studies have reported a change in the epidemiology, with

a doubling in incidence to around 1 in 1500 live
newborns.​
Causes
 Missing, poorly formed, or abnormally small
thyroid gland
 Genetic defect that affects thyroid hormone
production
 Too little iodine in the mother’s diet during
pregnancy
 Radioactive iodine or ant thyroid treatment for
thyroid cancer during pregnancy
 Use of medicines that disrupt thyroid hormone
production — such as ant thyroid drugs,
sulfonamides, or lithium — during pregnancy
Symptoms
 Symptoms include..
 thick, protruding tongue
 poor feeding
 choking episodes
 constipation
 prolonged jaundice
 short stature
 Myxedema
 Hypothyroidism marked by dry skin and swellings
around lips and nose as well as mental deterioration.
 Sign and symptoms
 Myxedema can occur in the lower leg (pretibial
myxedema) and behind the eyes (exophthalmos).
Pathophysiology
 Myxedema results from the accumulation of
increased amounts of hyaluronic acid and
chondroitin sulfate in the dermis in both lesional
and normal skin.
 The mechanism that causes myxedema is still not
yet understood, although animal model studies
suggest that thyroid hormones affect the synthesis
and catabolism of mucopolysaccharides and
collagen by dermal fibroblasts.
Laboratory Findings
 Increased serum TSH level
 Decreased serum free thyroxin
 Decreased serum total T4 and T3
 Decreased BMR
 Elevated serum cholesterol level

Imran Yousafzai
Hyperthyroidism
 Graves' disease
 It is an autoimmune disease, most commonly affects
the thyroid, frequently causing it to enlarge to twice its
size or more (goitre), become overactive, with
related hyperthyroidism.
 Toxic goiter: A goiter that is associated with
hyperthyroidism is described as a toxic goiter.
Examples of toxic goiters include diffuse toxic goiter
(Graves disease), toxic multinodular goiter, and toxic
adenoma (Plummer disease).
 symptoms
 Such as increased heartbeat, muscle weakness,
disturbed sleep, and irritability. It can also affect the
eyes, causing bulging eyes (exophthalmos). It affects
other systems of the body, including the skin, heart,
circulation and nervous system.
Cont..
Nervousness Dyspnea
Weight loss Stare, lid lag, lid retraction, and
Fatigue exophthalmos (with Graves’
Hair loss Weakness disease)
Tachycardia Diarrhea
Palpitations Emotional liability
Proximal myopathy Insomnia
Heat intolerance Hyperactive reflexes
Warm, moist skin Poor concentration
Excessive sweating Thyroid enlargement (in most
Hyperkinesis cases
Oligomenorrhea
Pathophysiology of hyperthyroidism
 Normally within the lymph node antigen presenting T
cells are present.
 During infection APC act like TSH receptors as a result
T cells produce B cells and then become plasma cells.
 Plasma cells make TSH receptor antibody all around
the body particularly it will cause edema in eyes and
legs.
 In hyperthyroidism the follicular cells become squeeze
and tall and also cause infiltration of T lymphocytes
which produce inflammatory mediators and leads to
inflammation.
 Parathyroid hormone (PTH), parathormone .
 The parathyroid glands are small endocrine glands in the
neck of humans and other tetrapod's that produce
parathyroid hormone. Humans usually have four
parathyroid glands, variably located on the back of the
thyroid gland, although considerable variation exists.
Parathyroid hormone and calcitonin (one of the
hormones made by the thyroid gland) have key roles in
regulating the amount of calcium in the blood and within
the bones.
 Calcitonin
It is a hormone secreted by the C cells of the thyroid gland.
Its main actions are to increase bone calcium content and
decrease blood calcium levels. Calcitonin opposes the
effects of parathyroid hormone, which acts to increase
the blood level of calcium.
Effect of hyper
parahyperthyroidism
 Effect of hyperthyroidism is bone loss from
osteoporosis, caused by an increased excretion of
calcium and phosphorus in the urine and stool. The
effects can be minimized if the hyperthyroidism is
treated early. Thyrotoxicosis can also augment calcium
levels in the blood by as much as 25%. This can cause
stomach upset, excessive urination, and impaired
kidney function
Effect of hypothyroidism
Effects of HT
 Liver
 Blood
 GI tract
 Nervous system
 Muscle
 CVS
 Lungs
 Skin
 Reproductive System
 kidney Imran Yousafzai
References
 Clinical Case - Anterior Triangle of the Neck.
 Dorland's (2012). Illustrated medical dictionary. Elsevier Saunders.
p. 1072. ISBN 978-1-4160-6257-8.
 Dorland's (2012). Illustrated Medical Dictionary 32nd edition.
Elsevier Saunders. pp. 999 redirect to 1562. ISBN 978-1-4160-6257-
8.
 Yalçin B., Ozan H. (February 2006). "Detailed investigation of the
relationship between the inferior laryngeal nerve including
laryngeal branches and ligament of Berry". Journal of the
American College of Surgeons 202 (2): 291–6.
doi:10.1016/j.jamcollsurg.2005.09.025. PMID 16427555.
 Lemaire, David (2005-05-27). "eMedicine - Thyroid anatomy".
Retrieved 2008-01-19.
 Kamath, M. Aroon. "Are the ligaments of Berry the only reason
why the thyroid moves up with deglutition?". Doctors Lounge
Website. Retrieved August 24, 2010.
Neurological Disorders
Hammad
Nursing lecturer
KMU –INS
Objectives
By the end of session, participants would be able to:
1. Describe the concept of somatosensory pathway
2. Discuss the process of pain and pain gait theory. 3. Differentiate acute and chronic
pain
4. Discuss non pharmacologic interventions of pain management
 Pain
 Pain is a vital function of the nervous system in providing the
body with a warning of potential or actual injury. It is both a
sensory and emotional experience, affected by psychological
factors such as past experiences, beliefs about pain, fear or
anxiety.
Somatosensory pathway
 Ascending pathway:
 Step.1: Suppose in right hand injury, within effected area
there are immune cell called cytokines. The important one
is Prostaglandin PG in ascending tract. Sensory nerve fibers
response and through first order neuron the message
reaches in dorsal horn of cervical supine.
 Step 2: Within the dorsal horn there is synapse for second
order neuron. Synapses occur through the chemical
mediator Substance P. In right side of spinal cord there is
an important tract called spinothelamic tract or opposite
tract.
 Step 3: Second order neuron carry pain impulses by
crossing medulla, pond and midbrain and terminates in
thalamus where synapsis occur between second order
neuron and third order neuron.
 Step 4: Third order neuron carry impulses to higher region
of brain such as somatosensory cortex where pain is
perceive. If the injury is at right arm the pain will
perceived in right hemisphere
Descending pathway
 Controlling pain by inhibiting ascending pathway.
 Step1: Serotonergic and non nor adrenergic neuron are
activated in thalamus. Inerneurones are also being
activated and release Ankephalin opioid and endorphin,
which inhibit releasing of Substance P, as a result there
will be no communication between first and second order
neuron.(no synapsis occur) which help and control signal
going up.
 All an all ankephaline and endorphin inhibit
ascending pathway by gate control pain.
Pain Conduction System
C fiber
(chemosensitive) A-delta fibers
• Primary afferent fibers • Primary afferent
• Small diameter fibers
• Unmyelinated Slow • Large diameter
conducting • Myelinated
• Dull, slow’ or second’
• Fast conducting
pain conduction.
Responding to chemical, • Sharp, ‘fast’ or ‘first’
mechanical and thermal pain conduction
stimuli. A fiber carry pain up to
They all terminates into the the brains higher
area (subthelamic area)
region (entire cortex).
which is responsible for
ANS activity.
3/24/2024 8
Pain Process
 The neural mechanisms by which pain is perceived
involves a process that has four major steps:

 Transduction (from stimulus to spinal cord)

 Transmission ( from spinal cord to thalamus)
 Perception (from thalamus to somatosensory cortex)
 Modulation ( activity of descending pathway
Where Nociceptors are Located??
 Somatic structures (skin, muscles, connective tissue,
bones, joints);

 Visceral structures (visceral organs such as liver, gastro-

intestinal tract).
Noxious stimuli and responses
 Mechanical (pressure, swelling, abscess, incision, tumor
growth)

 Thermal (burn, scald)

 Chemical (excitatory neurotransmitter, toxic substance,

ischemia, infection).
Activation of different cortical areas
The reticular Limbic system
Somatosensory (thelamus and
system cortex (mid brain)
Autonomic and motor hypothalamus)
Perception and Emotional and
response to pain and interpretation of
for warning the behavioral responses
sensations. to pain.
individual to do
something. e.g. intensity, type and e.g. attention, mood,
location of the pain and motivation, and
e.g. automatically sensation and relates
removing a hand when also with processing
the sensation to past pain and past
it touches a hot experiences, memory
saucepan experiences of pain
and cognitive activities.
Types of Pain
Physiologic, which refers to the body’s protective mechanism
to avoid tissue injury.

Pathologic, which arises from tissue injury and inflammation or damage to

a portion of the nervous system.

Nociceptive (peripheral tissue injury)

Neuropathic (damage to peripheral nerves or spinal cord)
Visceral (stimulation of pain receptors in the thoracic or abdominal viscera)
Somatic (injury to tissues other than viscera, such as bones, joints, muscles and
skin)
Types of Pain based on time
period
Acute (arising from a
sudden stimulus such as Chronic (persisting beyond
surgery or trauma). the time normally associated
with tissue injury).
OR OR
May continue from May continue for more than
seconds to 6 months six months
FACTORS AFFECTING PAIN
 Age
 Previous experience with pain
 Situational factors
 Socio-cultural
 Sex
 Meaning of pain
 Stress & anxiety
 Fatigue & insomnia
What is Nonpharmacologic Pain Treatment?

 Nonpharmacological pain therapy refers to

interventions that do not involve the use of medications to
treat pain.
 Most common in hospitals are :
 Heat/cold therapy
 Relaxation techniques (breathing exercises)
 Distraction (active and passive)
 Guided imagery
 Massage
 Comfort positions
 Training and coaching
 Empathy from healthcare provider
Nonpharmacological Management of Pain

 The goals of non pharmacological interventions are to:

 Decrease fear
 Reduce distress and anxiety
 Reduce pain
 Provide patients with a sense of control
Cognitive-Behavioral Techniques
•Helps divert attention away from procedures and may be directed at
the patient, caregiver or parent.

 Types of Cognitive-Behavioral Interventions

 Psychological preparation, education, information
 Distraction(passive or active): Video games, TV, movies, phone

 Relaxation techniques (breathing, meditation, etc.)

 Music therapy
 Guided imagery
 Training and coaching
 Coping statements: "I can do this” or “this will be over soon”
References
• Vaajoki A (2013). We have to take Pain Definition, Pain
Management, and the Results of Non-pharmacological Studies
Seriously. Vaajoki, Altern Integ Med, (2) 7

• The Anatomy and Physiology of Pain. Retrieved from:

http://www.ncbi.nlm.nih.gov/books/NBK219252/

• DeLaune, S.C., & Ladner, P.K (2002). Fundamentals of Nursing: St

a n d a r d s & pr a c t i c e (2nd ed), USA.

• Wood, S (2008). Nursing Times; Anatomy and physiology of pain.

Retrieved by: https://www.nursingtimes.net/clinical-archive/pain-
management/anatomy-and-physiology-of-pain/1860931.article
Cerebral Circulation & Stroke , Transient
Ischemic Attacks
Hamad
Nursing lecturer
KMU –INS
OBJECTIVES
 Review the major vessels in the cerebral circulation.

 Review the blood brain barrier and its function.

 Explain the degeneration of the nervous tissue that

cause alteration in cerebral blood flow (stroke).

 Identify risk factors contributing to CVA/TIA

 Discuss pathophysiology of CVA

22
Laila Ruknuddin Sewani, AKUSON 23
Cerebral Circulation

 The greater part of the brain is supplied with arterial blood by an

arrangement of arteries called the circulus arteriosus or the circle
of Willis.
 Four large arteries contribute to its formation: the two internal
carotid arteries and the two vertebral arteries.
 The vertebral arteries arise from the subclavian arteries, pass
upwards through the foramina in the transverse processes of the
cervical vertebrae, enter the skull through the foramen magnum,
then join to form the basilar artery.
 The arrangement in the circle of Willis is such that the brain as a
whole receives an adequate blood supply even when a contributing
artery is damaged and during extreme movements of the head and
neck.

24
Cerebral Circulation
 Anteriorly, the two anterior cerebral arteries arise from the
internal carotid arteries and are joined by the anterior
communicating artery.
 Posteriorly, the two vertebral arteries join to form the basilar
artery. After travelling for a short distance the basilar artery
divides to form two posterior cerebral arteries, each of which is
joined to the corresponding internal carotid artery by a posterior
communicating artery, completing the circle.
 From this circle, the anterior cerebral arteries pass forward to
supply the anterior part of the brain, the middle cerebral arteries
pass laterally to supply the sides of the brain, and the posterior
cerebral arteries supply the posterior part of the brain.
 Branches of the basilar artery supply parts of the brain stem.

25
 Cerebral Circulation
 The circulus arteriosus or circle of Willis is therefore
formed by:

 2 anterior cerebral arteries

 2 internal carotid arteries
 1 anterior communicating
 2 posterior communicating
 2 posterior cerebral arteries
 1 basilar artery

26
Cerebral Blood Flow

 The blood flow to the brain is maintained at approximately 750

mL/minute or one sixth or 20% of the resting cardiac output.
 Cerebral autoregulation is the ability of the brain to maintain
constant cerebral blood flow despite changes in systemic arterial
pressure.
 This allows the cerebral cortex to adjust cerebral blood flow
locally to satisfy its metabolic needs. The autoregulation of
cerebral blood flow is efficient within an MAP range of
approximately 60 to 140 mm Hg.
 If blood pressure falls below 60 mm Hg, cerebral blood flow
becomes severely compromised, and if it rises above the upper
limit of autoregulation, blood flow increases rapidly and
overstretches the cerebral vessels.
27
Venous Return
 Venous blood from the head and neck is returned by deep
and superficial veins.

 Superficial veins return venous blood from the superficial

structures of the face and scalp and unite to form the
external jugular vein.

 Venous blood from the deep areas of the brain is collected

into channels called the dural venous sinuses which are
formed by layers of dura mater lined with endothelium.
28
Venous Return
 The main venous sinuses are listed below:
 The superior sagittal sinus carries the venous blood from the
superior part of the brain.
 The inferior sagittal sinus lies deep within the brain and passes
backwards to form the straight sinus.
 The straight sinus runs backwards and downwards to become
the left transverse sinus.
 The transverse sinuses begin in the occipital region. They run
forward and medially in a curved groove of the skull, to become
continuous with the sigmoid sinuses.
 The sigmoid sinuses are a continuation of the transverse sinuses.
Inferiorly it continues as the internal jugular vein which unite
with the subclavian veins, carrying blood from the upper limbs,
to form the brachiocephalic veins. 29
Venous Return

30
 Blood–Brain Barrier (BBB)

 Astrocytes, the main supporting tissue of the central nervous system,

are found in large numbers adjacent to blood vessels with their foot
processes forming a sleeve round them.
 This means that the blood is separated from the neurons by the
capillary wall (Endothelial cells and its basement membrane) and a
layer of astrocyte foot processes which together constitute the blood–
brain barrier.
 The blood–brain barrier is a selective barrier that protects the brain
from potentially toxic substances and chemical variations in the blood.
 Oxygen, carbon dioxide, glucose and other lipid-soluble substances,
e.g. alcohol, quickly cross the barrier into the brain. Some large
molecules, many drugs, inorganic ions and amino acids pass more
slowly from the blood to the brain.
31
The Meninges
 The brain and spinal cord are completely surrounded by three
layers of tissue, the meninges, lying between the skull and the
brain, and between the vertebral foramina and the spinal cord.
Named from outside inwards they are the:
 Dura mater
 Arachnoid mater
 Pia mater

 The dura and arachnoid maters are separated by a potential

space, the subdural space. The arachnoid and pia maters are
separated by the subarachnoid space, containing cerebrospinal
fluid.
32
33
34
Transient Ischemic Attacks (TIAs)
 Transient or temporary episode of neurological dysfunction caused
by focal/local brain, spinal cord, or retinal ischemia, without acute
infarction.
 A TIA reflects a temporary disturbance in focal cerebral blood flow,
which reverses before infarction occurs.
 The causes of TIAs are the same as those of ischemic stroke and
include atherosclerotic disease of cerebral vessels and emboli.
 Last for few seconds or minutes but no longer than 24 hours
 May serve as warning sign for impending stroke.
 Reversible Ischemic Neurologic Deficits (RIND): S/S similar to
TIA but last for more than 24 hours and resolve completely within
21 days without any neurological deficit.
35
 Transient Ischemic Attacks (TIAs)
 TIAs are important because they may provide warning of
impending stroke. 50 % of patients who suffer an ischemic
stroke will report having had a TIA, and may never have
sought treatment.
 There is a higher risk of early stroke after TIA, 10% to 15%
have a stroke within 3 months, with 50% occurring in 48
hours.
 Diagnosis of TIA before a stroke occurrence may allow
surgical or medical intervention that prevents an eventual
stroke and the associated neurologic deficits.

36
 Clinical Manifestations of TIA

 Symptoms of TIA may be similar to those of stroke and depend on location of

affected vessel.
 Weakness or numbness on one side of the body, inability to speak or
understand language, or lack of coordination-except they don’t last as long.
 Any combination of the symptoms described for stroke, lasting more than a
few seconds, should be considered as a possible TIA.
 Unexplained dizziness
 Sudden excruciating headache
 One additional common symptom of a TIA is transient monocular blindness,
also called amaurosis fugax (flight of darkness). This is a brief change or
distortion of vision in one eye that is often described as a misting, clouding,
blurring, spottiness, or the sensation that a blind is being drawn down over the
eye.
37
Diagnostic tests
 Auscultation for carotid bruits
 CT to rule out stroke or other neurologic deficit
 Doppler, computed tomographic angiography (CTA)
or MRA studies of carotid artery
 Cerebral angiogram
 ECG to assess atrial fibrillation
 Transthoracic or transesophageal echocardiography to
rule out valvular disorders

38
 Stroke (Brain Attack)

 Stroke is the syndrome (represent a group of diseases) of

acute focal neurologic deficit from a vascular disorder that
injures brain tissue
 A stroke occurs when a part of the brain is damaged
 Also called Cerebro-Vascular Accident (CVA) or Brain
Attack or Apoplexy,
 Refers to any functional abnormality of the central
nervous system that occurs when the normal blood supply
to brain is disrupted.
 The damage is often permanent, caused by either a
blockage or a rupture in a vessel supplying blood to the
brain. 40
Stroke
Definition

 CVA [Stroke] is a focal neurological deficit due to a

vascular lesion. It is usually of rapid onset and by
definition lasts longer than 24 hours if the patient
survives. It presents as weakness (either permanent or
transient) of limbs on one side often with loss or
disturbance of speech.

41
Risk Factors  Modifiable
 Lifestyle habits
 Nonmodifiable  History of smoking
 Chronic alcoholism
• Sex (men> women)  Obesity
• Race (Hispanic/Latino  Diet high in fat content
Americans)  Drug abuse
• Age (55 +)
 Pathological conditions:
• Family History of
 HTN
TIA/stroke)  Diabetes mellitus
 Cardiac disease
 Hypercoagulability
 Sickle cell disease
 Polycythemia
42
 Risk Factors
 High Blood Pressure: A major risk factor common to both coronary
heart disease and stroke, high blood pressure is present in 50 to 70
percent of stroke cases, depending primarily on the type of stroke.
 The long-term effects of the increased pressure damage the walls of the
arteries, making them more vulnerable to thickening or narrowing
(atherosclerosis) or rupture.
 Heart Disease: It is a strong risk factor for ischemic strokes. Damage
to the heart may make it more likely that clots will form within the
heart. These clots can break loose and travel to the brain, causing a
cardio-embolic stroke. Patients with evidence of coronary artery
disease, congestive heart failure, left ventricular hypertrophy
(enlargement of the left side of the heart), disease of the heart valves,
or arrhythmias (especially atrial fibrillation) have a several-fold
increase in the risk of stroke. 43
 Risk Factors
 Smoking: Smoking facilitates atherosclerosis (fatty
deposits (atheromas) inside the arterial walls) and appears
to be an independent risk factor for strokes that result
from a clot. It also seems to be a risk for strokes that result
from cerebral hemorrhage.
 Diabetes: People with diabetes are at greater risk for
stroke, just as they are for heart disease because it
facilitates atherosclerosis.
 Cholesterol: Studies have found a link between high
blood lipid levels and atherosclerosis in cerebral arteries,
but it is still unclear whether high cholesterol levels
significantly increase stroke risk. 44
Risk Factors
 Obesity and Inactivity: Obesity and a sedentary life-style
are risk factors for stroke primarily because they increase
the risk of high blood pressure, heart disease, and diabetes.
 Oral Contraceptives: Studies have suggested that oral
contraceptive use along with smoking is associated with
an increase in stroke risk, because estrogen in oral
contraceptives is believed to promote blood clotting.
 History of Transient Ischemic Attacks (TIAs): Studies
have found that that these “ministrokes” may be the most
reliable warning of an imminent “full” stroke. Anyone
who has had a TIA should do whatever possible
interventions to reduce other risk factors. 45
 Risk Factors
 Heredity And Family History: The chance of having a stroke
is higher for people who have a family history of this disease.
Part of the risk is due to inherited risk factors and part to
family life-styles (e.g. eating and exercise).
 Age: The risk of stroke rises significantly with age. After 55, it
more than doubles with each passing decade. Each year, about
1 percent of people between ages 65 and 74 have a stroke—
and 5 to 8 percent of people in that age group who have had a
TIA go on to stroke.
 An Earlier Stroke: Because the same factors that caused a
first stroke are likely to cause a subsequent one, the risk of
stroke for someone who has already had one is increased. 46
 Risk Factors
 Carotid Bruit: A bruit is a noise made by turbulent flow in a blood
vessel that usually can be heard only with a stethoscope. The most
common cause is a narrowing of an artery because of
atherosclerosis. Bruits tend to occur in the large arteries of the body,
including the carotid artery in the neck. Even in patients without
other symptoms, carotid stenosis (narrowing) and carotid bruits are
associated with an increased stroke rate of 5 percent each year.
 Other Risk Factors: These include an elevated hematocrit (ratio of
volume of red cells to the total volume of blood), geographic
location (especially the southeastern United States, which is
sometimes called the “stroke belt"), lower socioeconomic status, use
of cocaine and amphetamines, and high alcohol consumption.
Stroke deaths seem to occur more often during periods of extreme
heat or cold. 47
Classification of Stroke

48
 Ischemic Stroke

 There are two broad categories of stroke: ischemic and

hemorrhagic.
 Ischemic strokes are caused by cerebrovascular obstruction
by thrombosis or emboli.
 Ischemic strokes are caused by a lack of blood flow to the
brain and account for about 70-80 percent of all strokes.
 Ischemic stroke can be classified into five main mechanisms
of stroke subtypes and their frequency: 20% large artery
thrombosis (atherosclerotic disease), 25% small penetrating
artery thrombosis disease (lacunar stroke), 20% cardiogenic
embolism, 30% cryptogenic stroke (undetermined cause),
and 5% other. 49
 Ischemic Stroke
Large-Vessel (Thrombotic) Stroke
 This is the common type, caused by a clot (thrombus) that blocks blood
flow in an artery. The narrowing leads to a low flow state referred to as
ischemia. If the resulting lack of oxygen results in death of brain tissue and
permanent damage, the term cerebral infarction is used.
 In the cerebral circulation, atherosclerotic plaques are found most
commonly at arterial bifurcations. Common sites include larger vessels of
the brain, notably the origins of the internal carotid and vertebral arteries,
and junctions of the basilar and vertebral arteries.
 In the atherosclerotic process, plaque—an amalgam of fatty substances,
cholesterol, waste products of cells, calcium, and a blood-clotting material
called fibrin-builds up as thick, irregular deposits on the inner lining of an
artery. The irregular surfaces that plaque deposits create provide ideal
places for clots to form and grow larger to obstruct/block the flow of blood.
50
 Ischemic Stroke
Small-Vessel Stroke (Lacunar Infarct)
 Lacunar infarcts are small (1.5- to 2-cm) to very small (3- to 4-mm)
infarcts located in the deeper parts of the brain or in the brain stem.
 They result from occlusion of the smaller penetrating branches of large
cerebral arteries, commonly the middle cerebral and posterior cerebral
arteries. In the process of healing, lacunar infarcts leave behind small
cavities, or lacunae (“lakes”).
 The most common is a pure motor stroke as a result the patient develops
one-sided weakness without other symptoms.
 Similarly, a lacunar stroke in the thalamus can cause a pure sensory
stroke that leads to loss of sensation.
 Six basic causes of lacunar infarcts include: embolism, hypertension,
small-vessel occlusive disease, hematologic abnormalities, small
intracerebral hemorrhages, and vasospasm. 51
 Ischemic Stroke
Cardiogenic Embolic Stroke
 Embolus is a wandering clot
 An embolic stroke is caused by a wandering or moving blood clot
that travels from its origin to the brain. It usually affects the larger
proximal cerebral vessels, often lodging at bifurcations.
 The embolus travels quickly to the brain and becomes lodged in a
smaller artery through which it cannot pass.
 Emboli can be formed from calcium, cholesterol, air, blood proteins,
platelets, or by-products of an infection of the heart’s inner lining
(endocarditis).
 The most common cardiac conditions associated with emboli are
atrial fibrillation, valvular disease, the presence of a prosthetic heart
valve, endocarditis, congestive heart failure, and myocardial
infarction.
52
The most frequent sites of arterial and
cardiac abnormalities causing ischemic stroke.

53
Ischemic Stroke
Pathophysiology
Atherosclerotic plaques ( thrombus)
( Large cerebral arteries)

Occlusion of the artery

Ischemia of the respective brain area

Inadequate delivery of blood

( oxygen + nutrients) to brain tissues
Ischemic Stroke
Pathophysiology Contd….

Oxygen deprivation for more than 3-4 mins

Infarction

Edema of the brain tissues

58
Ischemic Stroke

Laila Ruknuddin Sewani, AKUSON 59

Laila Ruknuddin Sewani, AKUSON 60
Ischemic penumbra
•In the evolution of a stroke ,there is
usually central core of dead and
dying cells, surrounded by ischemic
area of minimally perfused cells
called penumbra.
•Brain cell of penumbra receive
marginal blood flow, there metabolic
activities are impaired.
•Electrical activity of the cells fails
but structural integrity is maintained
 Hemorrhagic Stroke
 The most frequently fatal stroke results from the spontaneous rupture
of a cerebral blood vessel.
 Hemorrhage accounts for about 20 to 25 percent of all strokes. In
these strokes, blood seeps from a hole in a blood vessel wall into
either the brain itself (intracerebral hemorrhage) or the space around
the brain (subarachnoid hemorrhage).
 The resulting hemorrhage can cause a focal hematoma, edema, and
compression of the brain contents.
 The most common predisposing factors are advancing age and
hypertension. Other causes of hemorrhage are trauma, erosion of the
vessels by tumors, blood coagulation disorders, vasculitis, and drugs.
Aneurysms and arteriovenous malformations are structural
abnormalities that can also cause sudden hemorrhage.
 Along with other signs of stroke, vomiting and headache often occurs
at the onset. 64
Causes of Hemorrhagic Stroke
 Hypertension
 Advanced age
 Head injury
 Aneurysm
 Erosion of the vessels by tumor
 Vasculitis
 Drugs
 Blood coagulation disorders
 Hemorrhagic Stroke
 Increased BP increased pressure in cerebral blood vessels
rupture of vessel and leakage in surrounding tissues
hematoma increased pressure on surrounding brain tissue
increased ICP compensatory decrease in blood circulation
cell death and herniation of brain

66
Hemorrhagic Stroke

Laila Ruknuddin Sewani, AKUSON 67

 Brain or Intracerebral Hemorrhage

 In this type of hemorrhagic stroke, blood leaks from small

vessels at the base of the brain. Long-term exposure to high
blood pressure is thought to weaken the walls of these small
arteries, and eventually they burst.
 About two-thirds of patients with an intracerebral hemorrhage
have a history of hypertension; diabetes and atherosclerosis
accelerate the damage. Other causes of bleeding into the brain
include brain tumor, trauma, arteriovenous malformation
(AVM), and stimulant drugs such as amphetamines and cocaine.
 Intracerebral hemorrhage accounts for about 10 to 15 percent of
all strokes. The onset of symptoms is usually acute, with severe
headaches and decreased consciousness. Other symptoms
depend on the size and location of the hemorrhage. 69
 Aneurysmal Subarachnoid Hemorrhage
 Aneurysmal subarachnoid hemorrhage is a type of hemorrhagic
stroke caused by the rupture of a cerebral aneurysm and the
resulting bleeding into the subarachnoid space can extend well
beyond the site of origin.
 An aneurysm is a bulge at the site of a localized weakness in the
muscular wall of an arterial vessel.
 Most cerebral aneurysms are small saccular aneurysms called
berry aneurysms. They usually occur in the anterior circulation
and are found at bifurcations and other junctions of vessels such
as those in the circle of Willis.
 The incidence is higher in people with certain disorders,
including polycystic kidney disease, fibromuscular dysplasia,
coarctation of the aorta, and arteriovenous malformations of the
brain. 70
Common Sites of Berry Aneurysms

71
 Clinical Manifestations of Cerebral Aneurysms
 Before Rupture: Most small aneurysms are asymptomatic.
Approximately 10% to 20% of people with subarachnoid
hemorrhage have a history of atypical headaches occurring days
to weeks before the onset of hemorrhage, suggesting the
presence of a small leak.
 After Rupture: The onset of subarachnoid aneurysmal rupture
often is signaled by a sudden and severe headache, described as
“the worst headache of my life”.
 If the bleeding is severe, the headache may be accompanied by
collapse and loss of consciousness, vomiting, nuchal rigidity
(neck stiffness) and photophobia (light intolerance); cranial
nerve deficits, especially cranial nerve II, and sometimes III and
IV (diplopia and blurred vision); stroke syndromes (focal motor
and sensory deficits); cerebral edema and increased ICP.
72
 Clinical Manifestations of Stroke
 S/S mainly depend on location of affected vessel
 Symptoms of stroke always are sudden in onset and focal and
usually are one-sided.
 Most common symptoms are a facial droop, arm weakness, and
slurred speech.
 Other frequent stroke symptoms are unilateral numbness, vision loss
in one eye (amaurosis fugax) or to one side (hemianopia), language
disturbance (aphasia), and sudden, unexplained imbalance or ataxia.
 Seizures and memory loss
 Carotid ischemia causes monocular visual loss or aphasia (dominant
hemisphere) or hemineglect (nondominant hemisphere),
contralateral sensory or motor loss, apraxia (inability to make
purposeful movements) and agnosia (inability to recognize objects).
 Vertebrobasilar ischemia induces ataxia, diplopia, hemianopia,
vertigo, cranial nerve deficits, contralateral hemiplegia, and arousal
defects. 73
Diagnostic Evaluation
 CT Scan
 MRI
 Carotid artery ultrasound/ Doppler sonography

75
Disorders of Special Senses Eyes & Ears
Presented by: Ishmal Islam
Nishad ali shinwari
4TH Semester
INS-KMU Peshawar
 Purpose & Objectives

After completion of this unit students will be able

Review the anatomy and physiology of eye and ear
Discuss some common visual and auditory
dysfunction…Glaucoma .Tinnitus & Hearing loss
 Anatomy of Eye
Eye is a spherical shape organ having diameter of 2.3 to 2.4 cm
and lies in a large bony socket called orbital or occular cavity .

1/6 part of eye is visible while 5/6 part is unvisible to us

External anatomy of eye

Eyelids (uper & lower)

Eye lashes
Eye brows
Canthuses or commissure
Palpabral fissure
Internal anatomy f eye
 Internal anatomy of eye
the structure of eye ball is consist of three layers
1. the outer fibrous layer : sclera and cornea
2. the middle vascular layer: choroid, cillary body ,iris and puiple
3. the inner nervous layer : retina
structures inside the eye ball are lense, aqueous humourous
and vitrous humourous
Internal anatomy of eye
 GLAUCOMA .
Definition :
Glaucoma is a group of eye diseases that can cause vision
loss and blindness by damaging the optic nerve due to
increase intra occular pressure (IOP).
normal IOP is from 11 to 21 mmHg above that →
glaucoma developed
 causes
Age related
Family history
Ethnicity
 Medical conditions: Certain medical conditions, such as
diabetes, high blood pressure, heart disease, and hypothyroidism
 Increased intraocular pressure: This is the most significant risk
factor for glaucoma.
 Pathophysiology of glaucoma
Intraocular pressure (IOP): This is the pressure inside the
eye, which is determined by the balance between the
production and drainage of a fluid called aqueous humor.
The aqueous humor flows through the anterior chamber of
the eye and drains out through the trabecular meshwork . If
the drainage is blocked or impaired, the fluid accumulates
and increases the IOP.however some time problem arises
with the cillary body which start increase production of
aqueous humor . High IOP can compress and damage the
optic nerve and the blood vessels that supply it.
 continue
However, some people can have glaucoma with normal
or low IOP, and some people can have high IOP without
glaucoma. This suggests that other factors are also
involved in the pathophysiology of glaucoma.
 Types of Glaucoma .
• Open angle glaucoma .
in open angle glaucoma the angle in the eye where the iris meets the
cornea is as wide and open as it should be , but the eyes drainage canals
become blocked over time causing in increase in internal eye pressure
and subsequent damage to the optic nerve .
 Closed angle or narrow angle glaucoma .
Closed-angle glaucoma (also known as angle-closure glaucoma) occurs
when the drainage angle of the eye becomes completely blocked,
causing a sudden and severe increase in intraocular pressure. Some
causes of closed-angle glaucoma include Narrow drainage angle
sign and symptoms
 Treatment continue
1. Eye drops: Medications in the form of eye drops are
commonly prescribed to lower intraocular pressure. These
eye drops work by either reducing the production of aqueous
humor in the eye or improving its drainage
2.Laser therapy: Different types of laser therapy can be used
to treat glaucoma. These procedures aim to improve the
drainage of fluid from the eye or to decrease its production.
Examples of laser therapy include laser trabeculoplasty
 What is Ear?
• Human ear is the organ of hearing and equilibrium that detects
and analyzes sound.

• It is a sense organ that serves two different functions:

1) Hearing
2) Postural equilibrium (coordination of head and eye
movements)
 Anatomy of Ear
• Ear is divided into three main regions
1) Outer ear
2) Middle ear
3) Inner ear

Outer Ear Middle Ear Inner Ear

• Auricle or Pinna • Malleus • Semi-circular Canal

• External Auditory Canal • Incus • Cochlea
• Stapes • vestibules
Anatomy of Ear
Physiology of Hearing
 Disorders of the Ear
Tinnitus
• Tinnitus is when you experience ringing or other noises in one or both of your
ears.
• The noise you hear when you have tinnitus isn't caused by an external
sound, and other people usually can't hear it.
• Tinnitus is a common problem.
• It affects about 15% to 20% of people, and is especially common in older
adults.
 Pathophysiology of Tinnitus
• Neurophysiologically …Tinnitus is the consequences of brains response to
input deprivation from the auditory periphery”
• Leaver et al(2011 ) suggest that tinnitus occurs due to abnormal function
of the limbic system, which controls emotion.
• Suggest links to depression, anxiety.
• In a healthy cochlea ,there is a tonotopic organization .
• Signal travels from the cochlea to the mid brain to the auditory cortex.
• Tonotopy in the auditory system begins at cochlea the small snail like
structure in the inner ear that sense information about sound to brain.
 Causes of Tinnitus
Treatment
• Supportive care
• Age-related • No cure improves with time
• Exposure to loud noises • Identify underlying cause
• Impacted ear wax
• Inner or middle ear infection
• Neurological or muscular disease
• Side-effect of medication

Signs & Symptoms

• High pitched ringing in ears
• Humming, hissing, buzzing or roaring
• Impaired sleep
• Difficulty hearing others and
concentrating
 Hearing Loss

Hearing impairment refers to partial or total loss of hearing.

There are three types of hearing loss:

Sensorineural Mixed and functional
Conductive Hearing Loss Hearing Loss
Hearing Loss which occurs when
which occurs when the inner ear or which is a
there’s an auditory nerve is combination of the
obstruction of damaged two
sound wave
transmission
 Causes of hearing loss
• Impacted ear wax
• Trauma to the ear or head
• Loud noise
• Ototoxic medicines
• Work related ototoxic chemicals
• Nutritional deficiencies
• Viral infections and other ear conditions
• Delayed onset or progressive genetic hearing loss
 Treatment
• Removing earwax.
• Surgery: Some types of hearing loss can be treated with
surgery.
• Hearing aids. If hearing loss is from damage to the inner ear, a
hearing aid can be helpful.
• Cochlear implants
 References
• Porth pathophysiology
• Robbin pathology
• Myoclinic .com
• Understanding pathophysiology
 27-1

Cardiovascular Disorder
Hammad
Nursing Lecturer
KMU-INS

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-2

Introduction
 The cardiovascular system consists of heart and
blood vessels

 Sends blood to
 Lungs for oxygen
 Digestive system for nutrients

 CV system also circulates waste products to

certain organ systems for removal from the
blood
© 2009 The McGraw-Hill Companies, Inc. All rights reserved
The Heart: Structures
 Cone-shaped organ
about the size of a
loose fist
 In the mediastinum
 Extends from the level
of the second rib to
about the level of the
sixth rib
 Slightly left of the
midline

27-3
© 2009 The McGraw-Hill Companies, Inc. All rights reserved
 27-4

The Heart: Structures (cont.)

 Heart is bordered:
 Laterally by the lungs
 Posteriorly by the vertebral
column
 Anteriorly by the sternum

 Rests on the diaphragm

inferiorly

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-5

The Heart: Structures (cont.)

 Heart coverings
Click for Larger View
 Pericardium
 Covers the heart and large  Heart walls:
blood vessels attached to  Epicardium
the heart  Outermost layer
 Fat to cushion heart
 Visceral pericardium
 Innermost layer  Myocardium
 Middle layer
 Directly on the heart
 Primarily cardiac muscle
 Parietal pericardium
 Endocardium
 Layer on top of the visceral
 Innermost layer
pericardium
 Thin and smooth
 Stretches as the heart pumps

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-7

The Heart: Structures (cont.)

 Four chambers
 Two atria  Two ventricles
 Upper chambers  Lower chambers
 Left and right  Left and right
 Separated by  Separated by
interatrial septum interventricular
septum
 Atrioventricular septum separates the atria
from the ventricles

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-8

The Heart: Structures (cont.)

 Tricuspid valve – prevents blood from flowing
back into the right atrium when the right ventricle
contracts
 Bicuspid valve – prevents blood from flowing
back into the left atrium when the left ventricle
contracts
 Pulmonary valve – prevents blood from flowing
back into the right ventricle
 Aortic valve – prevents blood from flowing back
into the left ventricle

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-10

The Heart: Blood Flow

Oxygenate
Deoxygenat d blood out
ed blood in Oxygenated
to body
from body blood in lungs

Deoxygenated
blood out
to lungs
Atria Contract Ventricles Contract
© 2009 The McGraw-Hill Companies, Inc. All rights reserved
 27-11

The Heart: Blood Flow (cont.)

Right Tricuspid Right Pulmonary
Atrium Valve Ventricle Valve

Body Lungs

Aortic Left Left Pulmonary

Bicuspid
Semilunar Semilunar
Ventricle Valve Atrium
Valve Valve

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-12

The Heart: Cardiac Cycle

 One heartbeat = one cardiac cycle
 Atria contract and relax
 Ventricles contract and relax

 Right atrium contracts  Left atrium contracts

 Tricuspid valve opens  Bicuspid valve opens
 Blood fills right ventricle  Blood fills left ventricle

 Right ventricle contracts  Left ventricle contracts

 Tricuspid valve closes  Bicuspid valve closes
 Pulmonary semilunar valve  Aortic semilunar valve opens
opens
 Blood pushed into aorta
 Blood flows into pulmonary
artery

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-13

The Heart: Cardiac Cycle (cont.)

 Influenced by
 Exercise
 Parasympathetic nerves
 Sympathetic nerves
 Cardiac control center
 Body temperature
 Potassium ions
 Calcium ions

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-14

The Heart: Heart Sounds

 One cardiac cycle – two heart sounds (lubb and dubb)
when valves in the heart snap shut
 Lubb – First sound
 When the ventricles contract, the tricuspid and bicuspid
valves snap shut
 Dubb – Second sound
 When the atria contract and the pulmonary and aortic valves
snap shut

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-15

The Heart: Cardiac Conduction System

 Group of structures that send electrical impulses through the heart

 Sinoatrial node (SA node)  Bundle of His

 Wall of right atrium  Between ventricles
 Generates impulse  Two branches
 Natural pacemaker  Sends impulse to Purkinje fibers
 Sends impulse to AV node
 Purkinje fibers
 Atrioventricular node (AV  Lateral walls of ventricles
node)  Ventricles contract
 Between atria just above ventricles
 Atria contract
 Sends impulse to the bundle of His

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-17

Circulation
 Pulmonary circuit
right atrium  right ventricle  pulmonary
artery trunk  pulmonary arteries  lungs 
pulmonary veins  heart (left atrium)

 Systemic circuit
left atrium  left ventricle  aorta  arteries 
arterioles  capillaries  venules  veins 
vena cava  heart (right atrium)

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-18

Circulation (cont.)
 Arterial system
 Carry oxygen-rich blood
away from the heart

 Pulmonary arteries carry

oxygen-poor blood

 Paired – left and right

artery of the same name

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-19

Circulation (cont.)
 Venous system  Hepatic portal system
 Carries oxygen-poor  Collection of veins
blood toward the carrying blood to the
heart
liver
 Except pulmonary veins
 Most large veins have
the same names as
the arteries they are
next to

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-21

Chest Pain
 Cardiac  Non-cardiac
 Myocardial infarction  Heartburn
 Angina  Panic attacks
 Pericarditis  Pleurisy
 Coronary spasm  Costochondritis
 Pulmonary embolism
 Sore muscles
Take all complaints of  Broken ribs
chest pain seriously!

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

Chest Pain (cont.)
 Determine cause
 Electrocardiogram
 Stress tests
 Blood tests
 Chest x-ray
 Nuclear scan
 Coronary
catheterization
 Echocardiogram
 Endoscopy

27-22
© 2009 The McGraw-Hill Companies, Inc. All rights reserved
Diseases and Disorders of the
Cardiovascular System
Disease Description
Anemia The blood does not have enough red blood cells
or hemoglobin to carry an adequate amount of
oxygen to the body’s cells
Aneurysm A ballooned, weakened arterial wall
Arrhythmias Abnormal heart rhythms
Carditis Inflammation of the heart
Endocarditis Inflammation of the innermost lining of the
heart, including valves
27-23
© 2009 The McGraw-Hill Companies, Inc. All rights reserved
Diseases and Disorders of the
Cardiovascular System (cont.)
Disease Description
Myocarditis Inflammation of the muscular layer of the heart
Pericarditis Inflammation of the membranes that surround
the heart (pericardium)
Congestive Weakening of the heart over time; heart is
Heart Failure unable to pump enough blood to meet body’s
needs
Coronary Artery Atherosclerosis; narrowing of coronary arteries
Disease (CAD) caused by hardening of the fatty plaque deposits
within the arteries
27-24
© 2009 The McGraw-Hill Companies, Inc. All rights reserved
Diseases and Disorders of the
Cardiovascular System (cont.)
Disease Description
Hypertension High blood pressure; consistent resting blood
pressure equal to or greater than 140/90 mm Hg
Leukemia Bone marrow produces a large number of
abnormal WBCs
Murmurs Abnormal heart sounds
Myocardial Heart attack; damage to cardiac muscle due to a
Infarction lack of blood supply
27-25
© 2009 The McGraw-Hill Companies, Inc. All rights reserved
Diseases and Disorders of the
Cardiovascular System (cont.)
Disease Description
Sickle Cell Abnormal hemoglobin causes RBCs to change
Anemia to a sickle shape; abnormal cells stick in
capillaries
Thalassemia Inherited form of anemia; defective hemoglobin
chain causes, small, pale, and short-lived RBCs
Thrombophlebitis Blood clots and inflammation develops in a vein

Varicose Veins Twisted, dilated veins

27-26
© 2009 The McGraw-Hill Companies, Inc. All rights reserved
 27-27

In Summary
 Cardiovascular system
 Transport system for body
 Heart, arteries, veins, and capillaries
 Blood
 Transport medium
 RBCs, WBCs, platelets, plasma
 Medical assistant
 Assists patients in understanding prevention and
treatments for cardiovascular problems

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-28

Factors effecting cardiac performance

in the light of Frank Starling and
Lapcalce‟s law

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-29

Frank-Starling Law:
Frank-Starling law, also known as the law of
the heart, describes the relationship between
preload and stroke volume (the amount of
blood ejected from the left ventricle with each
heartbeat). According to this law, cardiac
performance is influenced by the following
factors

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-30

Preload:
Preload refers to the initial stretching of the cardiac
muscle fibers just before contraction. An increase in
preload, typically due to an increase in venous return
(amount of blood returning to the heart), leads to a
greater stretch of the heart muscle fibers. This
increased stretch results in a more forceful contraction
and, consequently, a higher stroke volume

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-31

Afterload:
Afterload is the resistance that the heart must
overcome to eject blood into the arterial system. An
increase in afterload, as seen in conditions like
hypertension, makes it more difficult for the heart
to eject blood, leading to a decrease in stroke
volume. Conversely, a decrease in afterload allows
the heart to eject blood more easily, increasing
stroke volume.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-32

Contractility:
Contractility refers to the intrinsic ability of the cardiac
muscle to contract. Factors that affect contractility include
sympathetic stimulation (which increases contractility) and
certain medications (positive inotropic agents) that can either
enhance or diminish contractile force. Higher contractility
leads to greater stroke volume.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-33

Laplace's Law:
Laplace's Law relates the pressure inside a
cylindrical tube (like a blood vessel) to the
tension in its wall and its radius. It is often
used to explain the factors affecting the wall
tension in blood vessels and, by extension,
their structural adaptations.
The formula for Laplace's Law for a cylinder
is:
T = (P * r) / (2 * h)

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-34

Where:
P is the pressure inside the vessel.
T is the wall tension.
r is the radius of the vessel.
h: Wall Thickness - This represents the thickness of
the wall of the hollow sphere

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-35

Factors affecting blood vessel wall tension according to

Laplace's Law:
a. Radius (r): Laplace's Law shows that wall tension is directly
proportional to the radius of the vessel. A larger radius leads to
higher wall tension, which can increase the risk of vessel
rupture. This is why larger arteries have thicker walls to
withstand the increased tension.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-36

b. Wall Thickness: Although not explicitly

in the formula, thicker vessel walls can
better resist the tension generated by blood
pressure. Arteries have thicker walls than
veins for this reason.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-37

Laplace's Law helps us understand how vessel

radius and wall tension influence the structural
adaptations of blood vessels to maintain their
integrity under pressure. Both laws are essential
in understanding the dynamics of blood
circulation in the body.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 27-38

Poiseuille's Law

Poiseuille's Law is often used to explain the relationship

between the blood vessel radius and blood flow,
emphasizing that a small change in the radius of a blood
vessel can have a significant impact on blood flow. The law
states that flow is directly proportional to the fourth power of
the vessel radius and inversely proportional to vessel length
and blood viscosity.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 39

Atherosclerosis

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 40

Pathophysiology
 Hardening of the arteries is a process that often occurs with
aging. As you grow older, plaque buildup narrows your
arteries and makes them stiffer. These changes make it
harder for blood to flow through them.
 Clots may form in these narrowed arteries and block blood
flow. Pieces of plaque can also break off and move to
smaller blood vessels, blocking them.
 Either way, the blockage starves tissues of blood and
oxygen, which can result in damage or tissue death. This is
a common cause of heart attack and stroke.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 41

Symptoms
 Hardening of the arteries does not cause symptoms until
blood flow to part of the body becomes slowed or blocked.
 If the arteries to the heart become narrow, blood flow to
the heart can slow down or stop. This can cause chest pain
(stable angina), shortness of breath, and other symptoms.
 Narrowed or blocked arteries may also cause problems and
symptoms in your intestines, kidneys, legs, and brain.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 42

Diagnosis
 Physical exam
 A number of imaging tests may be used to see how well
blood moves through your arteries.
 Doppler tests use ultrasound or sound waves.
 Magnetic resonance arteriography (MRA) is a special type
of MRI scan
 Special CT scans called CT angiography
 Arteriograms or angiography use x-rays to see inside the
arteries.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 43

Treatment
 Lifestyle changes: Reducing the lifestyle risk factors that
lead to atherosclerosis will slow or stop the process. That
means a healthy diet, exercise, and no smoking. These
lifestyle changes won't remove blockages, but they’re
proven to lower the risk of heart attacks and strokes.
 Medication: Taking drugs for high cholesterol and high
blood pressure will slow and perhaps even halt the
progression of atherosclerosis, as well as lower your risk of
heart attacks and stroke.
 Angiography and stenting.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 44

References
• Genest J, Libby P. Lipoprotein disorders and cardiovascular disease. In:
Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart
Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia,
Pa: Saunders Elsevier; 2011:chap 47.
• Libby P. The vascular biology of atherosclerosis. In: Bonow RO, Mann
DL, Zipes DP, Libby P, eds.Braunwald's Heart Disease: A Textbook of
Cardiovascular Medicine. 9th ed. Philadelphia, Pa: Saunders Elsevier;
2011:chap 43.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 45

Angina pectoris

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 46

Angina pectoris
 Angina pectoris–commonly known as angina–
is chest pain due to ischemia of the heart muscle,
generally due to obstruction or spasm of the coronary
arteries.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 47

Etiology
 Atherosclerosis is the most common cause
of stenosis (narrowing of the blood vessels) of the
heart's arteries and, hence, angina pectoris. Some
people with chest pain have normal or minimal
narrowing of heart arteries; in these
patients, vasospasm is a more likely cause for the pain.
 Myocardial ischemia also can be the result of factors
affecting blood composition, such as reduced oxygen-
carrying capacity of blood, as seen with
severe anemia (low number of red blood cells), or
long-term smoking.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 48

Pathophysiology
 Angina results when there is an imbalance
between the heart's oxygen demand and supply.
This imbalance can result from an increase in
demand (e.g. during exercise) without a
proportional increase in supply (e.g. due to
obstruction or atherosclerosis of the coronary
arteries).

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 49

Types of Angina
 The major types of angina are
 Stable angina
 Unstable angina
 Variant angina.

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 50

Cont….
 Stable angina is the most common type of angina. It
occurs when the heart is working harder than usual.
Stable angina has a regular pattern. (“Pattern” refers to
how often the angina occurs, how severe it is, and what
factors trigger it). Rest or medicine relieve the pain.
 Unstable angina doesn't follow a pattern. It may
occur more often and be more severe than stable
angina. Unstable angina also can occur with or without
physical exertion, and rest or medicine may not relieve
the pain.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 51

Cont….
 Variant angina is rare. A spasm in a coronary artery
causes this type of angina. Variant angina usually occurs at
rest, and the pain can be severe.
 It usually happens between midnight and early
morning. Medicine can relieve this type of angina.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 52

Signs and symptoms

 Pain and discomfort are the main symptoms of
angina.
 Pain from angina also can occur in the arms,
shoulders, neck, jaw, throat, or back.
 Signs and symptoms such as nausea (feeling sick
to your stomach), fatigue (tiredness), shortness of
breath, sweating, light-headedness, and weakness
also may occur.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 53

Diagnosis
 Chest X Ray
 Stress Testing
 ECG (Electrocardiogram)
 Blood Test

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 54

Treatment
 Lifestyle Changes
 Nitroglycerin is the most commonly used nitrate
for angina. Nitroglycerin that dissolves under
tongue or between cheek and gum is used to
relieve angina episodes.
 Other medicines also are used to treat angina,
such as beta blockers, calcium channel blockers,
ACE inhibitors.

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

 55

THANK YOU

© 2009 The McGraw-Hill Companies, Inc. All rights reserved

Skeletal & Muscular system ,Metabolic & Inflammatory
bone diseases
Presented by;
Habib Ullah
Misbah Iqbal
Suhana Syed
INS-KMU Peshawar
 Objectives

After completing the lecture students will be able to learn:

 Anatomy and physiology of the musculoskeletal system.
 Trauma and injury.
 Trauma and injury of the skeletal structures
 Osteoporosis, Osteomalacia (Rickets), Hyperparathyroidism and Paget’s
Disease.
 Pathological processes of metabolic bone diseases.
 Rheumatoid Arthritis (Gout).
 Inflammatory Joint diseases.
 Skeletal System

The bones of the skeleton are divided into two groups:

 The Axial skeleton consists of the skull, vertebral column,
ribs and sternum. Together the bones forming these structures
constitute the central bony core of the body, the axis.
 The Appendicular skeleton consists of the upper limbs bones with
pectoral girdles and pelvic girdles with the lower limb bones.
 Axial skeleton

Skull(28):
The skull rests on the upper end of the vertebral column
and its bony structure is divided into two parts: the
cranium and the face.
Cranium(8):
•1 frontal bone • 2 parietal bones
• 2 temporal bones •1 occipital bone
• 1 sphenoid bone •1 ethmoid bone
 Axial skeleton

Face(14):
The skeleton of the face is formed by 14 bones in addition
to the frontal bone .
•2 zygomatic (cheek) •2 maxilla
•2 nasal bones •2 lacrimal bones
•1 vomer •2 palatine bones
•2 inferior conchae •1 mandible.
EAR(6):
• Malleus
• Incus
• Stapes
 Axial skeleton

Functions of the skull:

The various parts of the skull have specific and different functions:
• The cranium protects the brain.
• The bony eye sockets protect the eyes and give attachment to the muscles
that move them.
• The temporal bone protects the delicate structures of the inner ear.
• The maxilla and the mandible provide alveolar ridges in
• which the teeth are embedded.
• The mandible, controlled by muscles of the lower face,
allows chewing.
 Axial skeleton

Vertabral column:
Cervical_07
Thoracic_12
Lumber_05
Sacral_05
Coccyx_04
 Axial skeleton

Functions of the vertebral column

• Collectively the vertebral foramina form the vertebral canal, which provides a
strong bony protection for the delicate spinal cord lying within it
• The pedicles of adjacent vertebrae form intervertebral foramina, one on each
side, providing access to the spinal cord for spinal nerves, blood vessels and
lymph vessels.
• The numerous individual bones with their intervertebral discs allow
movement of the whole column.
• Support of the skull.
• The intervertebral discs act as shock absorbers, protecting the brain.
• Formation of the axis of the trunk, giving attachment to the ribs, shoulder
girdle and upper limbs, and the pelvic girdle and lower limbs.
 Axial skeleton

Rib Cage(24):
The thorax (thoracic cage) is formed by the sternum anteriorly, twelve
pairs of ribs forming the lateral bony cages, and the twelve thoracic vertebrae.
• True ribs __07pairs
• False ribs__03pairs
• Floating ribs__02pairs
Sternum(01):
 Appendicular skeleton

The appendicular skeleton consists of the:

• Shoulder girdle with the upper limbs.
• Pelvic girdle with the lower limbs.
Shoulder girdle:
The shoulder girdle consists of two clavicles and two scapulae.
Upper limbs:
Humerus_02 Radius_02
Ulna_02 Carpels_16
Metacarpels_10 Phalanges_28
 Appendicular skeleton

Pelvic Girdle:
Two coxal bones ;
• Ischium_02
• Illium_02
• Pubis_02
Lower Limbs:
Femur_02 Tibia_02 Fibula_02
Tarsals_14 Metatarsals_10 Phalanges_28
 Mascular System

Introduction:
• Bones and joints do not produce movement.
• The human body has more than 600 individual muscles.
• Muscles cause bones and supported structures to move by alternating
between contraction and relaxation.
Functions of Muscle:
– Movement
– Stability
– Control of body openings and passages
– Heat production
 Mascular System

 Face Muscles:
 Orbicularis Occuli
• Closes eyelid and compresses lacrimal glands
 Levator palpebrae (opens eye & raises upper lid
 Masseter (chewing)
 Orbicularis oris (closes & protrudes lips)
 Buccinator (compresses cheeks, blowing, suction)
 Zygomaticus minor and major
• Draws corners of mouth laterally and upward as in smiling and laughing
 Mascular System

 Neck Muscles:
 Sternocleidomastoid  Digastric
• Flexes neck and draws head down • Opens mouth by lowering mandible
 Scalenes • Raises hyoid bone
• Flex neck laterally and elevate ribs  Sternohyoid
1 &2 in inspiration • Depresses hyoid bone after
 Trapezius swallowing
• Abducts and extends neck  Thyrohyoid
• Raises larynx
 Arm Muscles

 Deltoid (abduct humerus)  Flexor carpi radialis

 Teres major (adduct and medially rotate • Flexes wrist
humerus)  Palmaris longus
 Teres minor (abduct and laterally rotate • Flexes wrist
humerus)  Flexor carpi ulnaris
 Biceps brachii (flexes elbow) • Flexes wrist
 Extensor carpi radialis
 Brachialis (flexes elbow)
 Extensor carpi ulnaris
 Triceps brachii (extends elbow)
 Flexor pollicis (longus, brevis)
 Pronator ( teres, quadratus)
• Flexes thumb
 pronates forearm  Extensor pollicis (longus, brevis)
 Supinator (teres, quadratus) • Extends thumb
 supinates forearm  Flexor digitorum (superfi, profun)
• Flexes fingers II—V
Arm Muscles
Hamstring Muscles
Hamstring Muscles. The
knee flexor muscles are a
group of three muscles
located in the posterior
thigh region on both sides
of the body. Their names
are:
1) Biceps Femoris
2) Semitendonosus
3) Semimembranosus.
 Trauma & Injury

Trauma:
Trauma is an emotional response to a terrible event like an accident,
rape, or natural disaster.
Injury:
Injury is physiological damage to the living tissue of any organism,
whether in humans, in other animals, or in plants.
_Bruises _Sprains _Strains _Joint injuries _Nose bleeding
 Skeletal Trauma & Injury

Skeletal trauma can be

divided into three major
groups of injuries to the
musculoskeletal system:
1. Fractures
2. Dislocations.
3. Fracture/dislocations.
 Metabolic bone disorders

Metabolic bone disorders result from abnormally low levels of

calcium and phosphorus, minerals that support the growth and
strength of the bones. Symptoms include aching bones and frequent
fractures in older adults, or delayed bone growth in children.
Metabolic bone disorders are ;
 Osteoporosis.
 Osteomalacia.
 Hyperparathyroidism.
 Paget’s diseases.
 Osteoporosis

Osteoporosis:
Osteoporosis is a bone disease that develops when bone mineral density
and bone mass decreases, or when the structure and strength of bone
changes. This can lead to a decrease in bone strength that can increase the
risk of fractures (broken bones).
Causes:
_Sex _age
_body size _race
_diet _family history
_medical condition _hormones
 Osteoporosis
Symptoms
Osteoporosis is called a “silent” disease” because there are typically no
symptoms until a bone is broken.
Symptoms of vertebral (spine) fracture include:
_severe back pain
_loss of height, or spine malformations such as a stooped or hunched posture
(kyphosis).
Pathophysiology:
In adults, the daily removal of small amounts of bone mineral, a process
called resorption, is balanced by an equal deposition of new mineral in order to
maintain bone strength. When this balance tips toward excessive resorption, bones
weaken and over time can become brittle and prone to fracture (osteoporosis).
 Osteoporosis

Diagnosis: Treatment:
• X-rays • Diet
• CT scan • Hormonal therapy
• Bone density test • Life style modification
The test uses X-rays to measure how many Medications
grams of calcium and other bone minerals are
packed into a segment of bone. The bones • PTH analogue
that are most commonly tested are in the • Denosumab
spine, hip and sometimes the forearm.
• Romosozumab
• Ultrasound
 Osteomalacia

Osteomalacia:
A disorder of “bone softening” in adults that is usually due to prolonged
deficiency of vitamin D.
Causes:
_Vit D deficiency _Digestive/kidney disorder
(Vitamin D is essential for calcium absorption and for maintaining bone
health. These disorders can interfere with the body's ability to absorb vitamins.)
_Genetic conditions
Symptoms:
_Pain in bones and hips _Bone fractures
_Muscles weakness _Difficulty in walking
 Osteomalacia

Pathophysiology:
Pathophysiology in rickets/osteomalacia is defect in vitamin D actions
and/or hypophosphatemia. Vitamin D deficiency, inability of activation of vitamin
D in vivo or functional derangement in vitamin D receptor is involved in impaired
actions of vitamin D.
Diagnosis:
 The most important indicator is low levels of vitamin D.
 X-rays may be taken to see if there is any evidence of osteomalacia.
 A bone mineral density scan may be helpful in evaluating the amount of
calcium and other minerals present in a patient’s bone segment.
 Osteomalacia

Treatment:
Patients who have osteomalacia can take vitamin D, calcium or
phosphate supplements, depending on the individual case. For instance, people
with intestinal malabsorption (the intestines cannot absorb nutrients or vitamins
properly) may need to take larger quantities of vitamin D and calcium.
• Wearing braces to reduce or prevent bone irregularities.
• Surgery to correct bone deformities (in severe cases).
• Adequate exposure to sunlight.
 Hyperparathyroidism

Hyperparathyroidism:
Hyperparathyroidism is where the parathyroid glands (in the neck, near
the thyroid gland) produce too much parathyroid hormone.
Primary hyperparathyroidism:
Primary hyperparathyroidism occurs
because of a problem with one or more of
the four parathyroid glands:
 A noncancerous growth (adenoma) on a gland
is the most common cause.
 Enlargement (hyperplasia) of two or more parathyroid
glands accounts for most other cases.
 A cancerous tumor is a very rare cause of
primary hyperparathyroidism.
 Hyperparathyroidism

Secondary hyperparathyroidism:
Secondary hyperparathyroidism is the result of another condition that
lowers the blood calcium, which then affects the gland's function.
Factors that may result in secondary hyperparathyroidism include:
 Severe calcium deficiency.
 Severe vitamin D deficiency.
 Chronic kidney failure.
 Hyperparathyroidism

Symptoms:
Symptoms may be so mild and nonspecific that they don't seem related
to parathyroid function, or they may be severe. The range of signs and
symptoms include:
 Weak bones that break easily (osteoporosis).
 Kidney stones.
 Stomach (abdominal) pain.
 Tiring easily or weakness.
 Bone and joint pain.
 Frequent complaints of illness with no clear cause.
 Nausea, vomiting or loss of appetite.
 Hyperparathyroidism

Diagnosis:
_Blood test _Bone mineral density test _Urine test
_Sestamibi parathyroid scan.
Sestamibi is a radioactive compound that is absorbed by overactive parathyroid glands.
It can be detected by a scanner that detects radioactivity.
Treatment:
Watchful waiting:
Your health care provider may recommend no treatment and regular monitoring if:
 Your calcium levels are only slightly elevated.
 Your kidneys are working well, and you have no kidney stones.
 Your bone density is within the standard range or only slightly below the range.
 You have no other symptoms that may improve with treatment.
 Hyperparathyroidism

Medications:
 Calcimimetics_A calcimimetic is a drug that mimics calcium circulating in the blood. The
drug may trick the parathyroid glands into releasing less parathyroid hormone. This drug is
sold as cinacalcet (Sensipar).
 Hormone replacement therapy_For women who have gone through menopause and
have signs of osteoporosis, hormone replacement therapy may help bones keep calcium.
However, this treatment doesn't address the underlying problems with the parathyroid
glands.
 Bisphosphonates_ Bisphosphonates also prevent the loss of calcium from bones and
may lessen osteoporosis caused by hyperparathyroidism.
 Hyperparathyroidism

Surgery:
Surgery is the most common treatment for primary hyperparathyroidism
and provides a cure in most cases. A surgeon will remove only those glands
that are enlarged or have a tumor.
If all four glands are affected, a surgeon will likely remove only three
glands and perhaps a portion of the fourth — leaving some functioning
parathyroid tissue.
 Paget's disease

Paget's disease:
Paget's disease of bone is a
chronic (long-lasting) disorder that
causes bones to grow larger and
become weaker than normal.
Causes:
 Genetic factors
 Environmental triggers
 Increasing Age
 Ancestry
 Paget’s disease
Pathophysiology:
Increased osteoclast activity lead to excessive bone resorption

Release of pro-inflammatory cytokines and growth factors

Stimulation of osteoblast activity

Formation of structurally abnormal bone

Ongoing bone remodeling cycle thickened, dense bones prone to fracture

 Paget's disease

 Diagnosis:
 Imaging tests
Bone changes can be revealed by:
 X-rays: The first indication of Paget's disease of bone is often abnormalities found on X-
rays done for other reasons. X-ray images of your bones can show areas of bone
breakdown, enlargement of the bone and deformities that are characteristic of the disease,
such as bowing of your long bones.
 Bone scan: In a bone scan, radioactive material is injected into your body. This material
travels to the spots on your bones most affected, and they light up on the scan images
 Lab tests: People who have Paget's disease of bone usually have elevated levels of
alkaline phosphatase in their blood, which can be revealed by a blood test.
 Paget's disease
 Medications:
Osteoporosis drugs (bisphosphonates) are the most common treatment
for Paget's disease of bone. Bisphosphonates are typically given by injection
into a vein, but they can also be taken by mouth. When taken orally,
bisphosphonates are generally well tolerated but can irritate the stomach.
o Bisphosphonates that are given intravenously include:
• Zoledronic acid (Zometa, Reclast)
• Pamidronate (Aredia)
• Ibandronate (Boniva)
o Oral bisphosphonates include:
• Alendronate (Fosamax, Binosto)
• Risedronate (Actonel, Atelvia)
 Inflamatory Joints Diseases

 Definition:
Inflammatory joint disease is commonly called arthritis. Inflammatory joint
disease is characterized by inflammatory damage or destruction in the synovial
membrane or articular cartilage and by systemic signs of inflammation (fever,
leukocytosis, malaise, anorexia, hyperfibrinogenemia).
 Some of the inflammatory joint diseases are :
 Rheumatoid arthritis
 Gout
 Rheumatoid arthritis

Definition:
Rheumatoid arthritis, or RA, is an autoimmune
and inflammatory disease, which means that your
immune system attacks healthy cells in your body
by mistake, causing inflammation (painful swelling)
in the affected parts of the body specifically joints.
 Causes:
Doctors don't know what starts this process, although a genetic
component appears likely. While your genes don't actually cause rheumatoid
arthritis, they can make you more likely to react to environmental factors —
such as infection with certain viruses and bacteria — that may trigger the
disease.
 Rheumatoid arthritis
 Symptoms:
 Joint pain, swelling, and stiffness, especially in the hands and feet
 Fatigue, fever, and weight loss
 Joint deformities and loss of mobility in advanced cases
 Pathophysiology:
 Abnormal immune response: The body's immune system mistakenly attacks
the synovial membrane, a tissue that lines the joints.
 Inflammatory response: The synovial membrane becomes inflamed, leading
to swelling, pain, and stiffness in the affected joint(s).
 Joint damage: Over time, inflammation can damage cartilage, bone, and
other joint structures, leading to permanent joint deformities.
 Rheumatoid arthritis

 Diagnosis:
 Medical history and physical examination
 Laboratory tests, such as rheumatoid factor (RF) and anti-cyclic
citrullinated peptide (anti-CCP) antibody tests
 Imaging tests, such as X-rays and magnetic resonance imaging (MRI)
 Rheumatoid arthritis

 Treatment:
 Medications:
 Disease-modifying antirheumatic drugs (DMARDs) can slow or stop the
progression of RA and reduce joint damage. Examples include methotrexate, sulfasalazine,
and hydroxychloroquine.
 Biologic agents, such as TNF inhibitors or interleukin blockers, can target specific immune
system cells or molecules that contribute to RA inflammation.
 Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can provide
pain relief and reduce inflammation.
 Physical therapy and exercise can help improve joint function and mobility.
 Surgery, such as joint replacement or synovectomy, may be necessary in severe cases.
 Gout

 Definition:
Type of arthritis caused by uric acid crystal deposition in joints.
Commonly affects the big toe joint, but can occur in other joints.
 Cause of Gout:
 Having high urate levels.
 Having a family history of gout.
 Being male.
 Having menopause.
 Increasing age.
 Drinking alcohol.
 Gout

 Signs and Symptoms:

- Sudden and severe joint pain, often described as a burning sensation.
- Redness, swelling, and warmth in the affected joint.
- Recurrent attacks of symptoms over time.
 Pathophysiology:
- Uric acid crystal accumulation in the joint.
- Overproduction or under-excretion of uric acid.
- Triggers immune response and inflammation.
 Gout

 Diagnosis and Treatment:

- Diagnosis through symptoms, physical examination, and laboratory tests.
- Medications for pain and inflammation management.
- Drugs to lower uric acid levels.
- Dietary changes and lifestyle modifications.
 Bone Markers

Bone Formation Markers

MmMarkers NormalNormal Value
Osteocalcin 10-46 ng/mL
Alkaline phosphatase 20-140 U/L

Bone Resorption Markers:

mMarkers NNormal Vales
C- terminal telopeptide 0.01-0.37 ng/mL
N-terminal telopeptide 10-100 nmol
 References
• www.nhn.uk
• www.cdc.gov
• www.osmosis.org
• Porth pathophysiology edition 13th
 Objectives
• Anatomy and physiology of bone.
• Bone Tumors and Cancer.
• Pathological processes involved
in different types of Bone Tumors
and Cancer pathogenesis.
• Explain the pathogenesis and
manifestations bone of
tuberculosis.
 Connective tissue.
Bone Cells + Matrix (Intercellular substance).
Classification of Bones
Continued.....
 Bone Structure(Anatomy)
• Bones are composed of two types of tissue.

• Compact (cortical) bone; It makes up around 80% of

adult bone mass and forms the outer layer of bone.

• Cancellous (trabecular or spongy) bone makes up the

remaining 20% of bone and consists of a network of
trabeculae, or rod-like, structures. It is lighter, less dense,
and more flexible than compact bone.
• Precise arrengement of compact and spongy bone
depends on the type of bone.
 Long Bones contain tubular shaft (Diaphysis), made up of thick collar of compact bone , sorrounding a
medullary cavity (marrow cavity). in adults this cavity conatins yellow bone marrow , which is high in fat.
End of long bones called epiphysis (spongy bone inside compact bone) , contain red marrow which produce
blood cells.
 Epiphyseal line, which is a remnant of the epiphyseal plate, a disc

of cartilage that grows during childhood, which is how these bones get longer as a child gets taller.
Function Of Bone
Bone Tumors and Cancer
 The mesoderm contributes the primitive fibroblast and reticulum cells. The
fibroblast is the progenitor of the osteoblast and chondroblast cells. Each cell
synthesizes a specific type of intercellular ground substance, and the type of ground
substance produced by the cell generally characterizes the tumor derived from that
cell.
 Osteosarcoma. A, Common locations of Ewing sarcoma and osteosarcoma.
Blue, osteosarcoma;red, Ewing sarcoma. B, Comparison of plain radiograph, MRI, and nuclear
bone scan appearances of osteosarcoma of the distal femur. Note destruction of the bone
cortex and soft tissue component.
Primary Tumors (Benign)
Primary Tumors (Malignant)
 Bone tuberculosis
• TB primarily affects the lungs, but in some cases it
can spread to other parts of the body. When TB
spreads, it’s referred to as extrapulmonary
tuberculosis (EPTB).
• One form of EPTB is bone and joint tuberculosis.
This makes up about 10 percent of all EPTB cases
in the United States. Bone tuberculosis is simply a
form of TB that affects the spine, the long bones,
and the joints.
 Causative agent and transmission
• Tuberculosis is caused by a rod-shaped bacterium, or a
bacillus, called Mycobacterium tuberculosis.
• An infection is initiated following inhalation of mycobacteria
present in aerosol droplets discharged into the atmosphere
by a person with an active infection.
• The transmission process is very efficient as these droplets
can persist in the atmosphere for several hours and the
infectious dose is very low – less than 10 bacilli are
needed to start the infection.
• Once in the lung, the bacteria meet with the body’s first-line
defense - the alveolar macrophages.
• The bacteria are ingested by the macrophages but manage to
survive inside. Internalization of the bacilli triggers an
inflammatory response that brings other defensive cells to the
area.Together, these cells form a mass of tissue, called a
granuloma, characteristic of the disease.
 Latent TB
• In its early stage, the granuloma has a core of infected
macrophages enclosed by other cells of the immune system.
As cellular immunity develops, macrophages loaded with
bacteria are killed, resulting in the formation of the caseous
center of the granuloma.
• The bacteria become dormant but may remain alive for
decades.This enclosed infection is referred to as latent
tuberculosis and may persist throughout life without causing
any symptoms.
• The strength of the body’s immune response determines
whether an infection is arrested.
 Active pulmonary tuberculosis.
• On the other hand, if the immune system is compromised
by immunosuppressive drugs, HIV infections, malnutrition,
aging, or other factors, the bacteria can be re-activated
replicate, escape from the granuloma and spread other
parts of the lungs causing active pulmonary
tuberculosis.
• This reactivation may occur months or even years after
the initial infection.
 Extra Pulmonary TB
• In some cases, the bacteria may also spread to other organs
of the body via the lymphatic system or the bloodstream.
• This widespread form of TB disease, called disseminated TB
or miliary TB, occurs most commonly in the very young, the
very old and those with HIV infections.
 Menifestations of Bone TB (pott disease)
• severe back pain
• fatigue ,fever,weight loss
• night sweats
• swelling
• stiffness
• abscesses
• neurological complications
• paraplegia/paralysis
• limb-shortening in children
• bone deformities
Management of Bone TB
References