Basic Sciences

Immunology
 Complement
Complement pathway
Classic pathway
Mannose + lectin
from bact cell wall C1qrs - C1 inhibitor, + immune complex

proteases
C2,4 - C4 binding protein

C3a, 5 a
chemotaxis C3 Alternate pathway
Properdin,
C3b
Factor B, D
opsonization
(C3bBb)
+ bact. Lipopolysac
C3 nephritic factor

- Membrane inhibitor - Decay accelerating factor

C5,6,7,8,9
of reactive lysis (MIRL) (DAF), factor H.
(MAC) cell lysis
 Complement deficiency
Def of Complement components;
1. Congenital def. of C2,4 IC clearance SLE, vasculitis, polymyositis.
2. C3 def Life threatening infection with encapsulated org. e.g. pneumococci.
3. MAC (C5,6,7,8,9) disseminated neisserial infection.
4. Acquired consumption occur in SLE, cryo, IEC, post infectious GN, MPGN.

Def of regulatory proteins;

1. Def of C1 inhibitor hereditary angioneurotic edema dt vasoactive C2
fragment, ttt with epinephrine in the acute attack & danazole for prevention
as it hepatic synthesis of C1 inhibitor & C4, SLE dt consumption of C2, 4.
2. PNH; def of membrane GP (GPI) which bind the inhibitory comp DAF.
3. HUS; familial type dt def of Factor H compl activation & end. Injury.
4. MPGN type 2; C3 nephritic factor, def factor H.
5. ACEI C1 inhibitor def angioedema.
6. Cryo; C4, preserved C3 dt C4 binding protein inact of C3.
 Ig G;
- Monomer formed of a divalent molecule ( 2Fab) 2 light and 2 Immunoglobulin
heavy chains.
- Most abundant.
- 2ry immune response.
- The only Ig that cross the placenta. Fab
- MW; 150.000 dalton (25 for each LC & 50 for HC).
- 4 subclasses according to Fc.
The reference range is 8-20 g/l.

Ig A;
- Monomer in serum, dimeric in secretion.
- Def chronic diarrhea, respiratory infection, autoimmune dis.
- IgA1 contain hinge region.
- Level undetectable at birth, reach adult level at puberty.

Ig M Fc
- pentameric.
- 1ry immune response.
- Secretion do not need Th2.
- Include Bl group Ab.
- Against bacteria.
- Level undetectable at birth, reach adult level at 1 yr.

Ig D on B cell surface.

Ig E;
produced by plasma cell, attach to mast cell & basophils,
responsible for type 1 hypersensitivity reaction.
 Hypersensitivity reactions
Type 1; anaphylactic or immediate
- Ag+ Ig E on mast cell
- diagnosed by plasma tryptase ( protease released from mast cell).
- e.g. asthma, atopy, drugs as latex, peanut.
Type 2; Ab-dependent cytotoxicity
- cell bound Ag + circulating Ig
- e.g. transfusion react, Rh, Goodpasture, ITP, Coomb's positive haemolytic
anaemia.
Type 3; IC-mediated or arthus reaction
- free Ag + free Ig
- e.g. excess Ig farmer lung, bird fancier, pulm aspergillosis.
excess AgGn, serum sickness.
Type4; cell-mediated or delayed hypersensitivity
- Ag on APC + T memory cells
- tuberculin, contact dermatitis, GVHD, graft rejection.
Type 5; stimulatory.
- Ab + cell surface receptor e.e. Graves.
 Cells of the immune system
PMN;
1. Neutrophils phagocytosis, bacteria.
- Phagocytes have a role in recognition and elimination
of microbes by reactive oxygen species or antigens by
opsonisation.
2. basophils & mast cells; type 1 hypersensitivity, parasites.
3. Eosinophils; allergy, helminthes, phagocytose IC.

Mononuclear;
1. Lymphocytes,
2. monocytes.
 Chronic granulomatous disease;
- It is a defect in the production of NADPH H
peroxide phagocytic function of neutrophils
(normal phagocytosis but defective intracellular
killing) chronic granulomas & microabcesses
in skin, bone & liver.
- Diagnosed by nitroblue tetrazolium test
(screening for reduced phagocytic capacity).
- Ttt; INF
 blood lymphocytes
1.5-3.5.000
20-40% of WBCs

T-cells B-cells natural killer (NK)

60 to 80 % 10 to 20 % 5 to 10 %.

Helper T-cells Suppressor/

60 to 70 % cytotoxic T-cells
(CD4+ cells) 30 to 40 %
Bind to (CD8+ cells).
class 2 MHC Ag
on APC as MQ
IL1,6, TNF

Active
CD4 Th Bind to
class 1 MHC Ag
IL2 On viral infected cells, cancer cells
IFN
IL12, 18 Th1 IL4

th1 IL10 th2

(-)
 T lymphocytes;
- The predominant cell type in the paracortical region of LN.
- Role; intracellular infections, tumour surveilance, graft
rejection.
- Arise in BM, mature in thymus.
- Types;
Cytotoxic (CD8) T cells recognise MHC class I
molecule antigens
T helper (CD4) cells recognise MHC class II molecule
antigens.
 Thymus- independent Ag;
- theses are mainly carbohydrate Ag
- e.g. pneumoccocal polysaccarides,
- activate B lymphocyte without TH cells
- polyclonal Ab mainly Ig M with poor affinity
& no memory.
 B lymphocytes;
- The predominant cell type in the germinal
follicle of LN.
- Arise in BM, mature in the spleen & LN.
NB:
- B cells usually require T cell help for full
activation. B cells are activated in primary
immune response which initially produce
IgM. CD40 & CD 40L are required for
costimulation of T cells, if either is
deficient impair Ig class switching.
 Natural killer cells;
- destroy viral infected & tumour cells.
- Rather than T cell receptors, natural killer
cells express adhesion molecules which
allow adhesion to target cells.
- CD94 receptor is located in Natural Killer
(NK) cells and is bound to the cell
membrane. It enables NK cells to
discriminate between healthy cells and
pathogen infected cells
 Major histocompatibility complex

DR/DP A, B, C
Class 2 class1
Class 3= C2,4, factor B

MHC is a group of genes on chr 6 that form HLA Ag & some CC.

class1
form HLA A,B,C transmemb peptide with B2
microglobulin
on All cells, allow self recognition.
Signal to CD8 cytotoxic cells (which are activated
when they see foreign class 1 Ag as
graft, virally infected cell, tumor cell.)
Class 2
HLA DR, DP, DQ
Immune cells; B cell, MQ &
some endothelial cells
CD4 Th, (class2 Ag on APC
present foreign Ag to Th
cells & protect their cells
from T cytot)
 Cytokines
Cytokines are low MW peptides produced by
lymphocytes, MQ and fibroblasts & have non
enzymatic biological activity,( local or systemic).
They include;
- Interleukins
- interferons
- CSFs
Certain patterns of Cytokine production;
- Acute phase reactants(IL1, 6, TNF ) derived from MQ.
- cell-mediated immunity; (IL2,INF) by Th1.
Ab-mediated immunity; (IL4,5,6,10) by Th2 & stimulate B
lymphocytes, maturation of dendritic cells .
- Antiinflammatory; (IL4, 10) by Th2.
IL-1;
Released by MQ B &T stimulation, acute phase reactant,
osteoclastic bone resorption.
Involved in;
- Rh arthritis IL-1 + collagenase, phospholipase,
cyclooxygenese (facilitator of damage).
- Atherosclerosis; endo uptake of LDL IL-1 PDGF.
- Septic shock IL1 NO, PG, PAF VD.
- Infection, acute graft rejection IL1 T & B lymph.

IL2; from Th1 growth of activated T cells, NK cells.

IL4, IL10; from Th2 inhibit cell mediated immunity, INF
(antiinflammatory cytokines), stimulate Ig production.
IL-5; from mast cells chemotaxis for esinophils.
IL6; from MQ acute phase reactant, stimulate Ig production.
 Tumour necrosis factor (TNF) ;
MQ, esinoph, NK.
T lymph .
TNF is procoagulant & lead to thrombosis.
dis associated; Rheumatoid, MS, MOF. So,
neutralizing Abs = anti-TNF are used.
not used in cancer highly toxic, + tumor
growth.
INF,; from WBC, fibroblasts antiviral
effects
. IFN and IFN (not ) bind to the same
receptor known as type I receptors. IFN is
used therapeutically in multiple sclerosis.

INF; Th1 activate MQ, inhibit Th2.

.
Therapeutic uses;
* INF HBV, HCV, hairy cell Keuk, cut T cell lymphoma, Kaposi
sarcoma in AIDs, RCC, condyloma acuminata.

* INF MS.

* INF chronic granulomatous dis.

* IL2 RCC, acute leukemia.

* GM-CSF correction of cytopenias e.g. during chemotherapy.

* interleukin receptor antagonists (IL-1Ra) are useful as disease

modifying drugs in rheumatoid arthritis (Anakinra).

* anti- TNF (infliximab, etanercept) are used in Rheumatoid,IBD.

 Eicosanoids
Def; are biologically active lipids, derived from the cellular
membrane phospholipids by the enzyme phospholipase
releasing arachydonic acid (or Omega 3 FA as an
exogenous source);
Lipooxygenase act upon arachydonic acid leukotrienes;
- LTB4 neutrophil chemotaxis, mucous secretion,
modulate cell growth.
- LTC4,D4,E4 (slow reacting substance of anaphylaxis)
vascular permeability, sm contraction, mucous secretion,
modulate cell growth.NB; LT receptor antagonists are used
in asthma.
Cyclooxygenase act upon arachydonic acid PG &
thromboxane.
- PG I2 (prostacyclin) released from endothelium VD, (-)
plat aggregation.used in 1ry pul HTN, HUS, Raynaulds.
- PGE2; immunomodulator, (-) lymphocyte proliferation,
cytokinr production, neutrophil function.
- PGD2; from mast cells anaphylaxis.
Congenital
Immune deficiency
Complement def.; encap org
- C3 life threatening pneumoc inf.
- MAC disseminated neisseria.
Neutrophil def Bact, candida.
- chronic granulomatous dis.
- Chediak Higashi
- lazy leukocyte S.
T cell def viral, mycobact, fungal, malig, parasites, fatal BCG & yellow
fever vaccine.
- Di George; non familial, def in thymus & 3rd & 4th branchial arches immun def,
absent PTH, aortic arch abn., cleft palate
B cell def Bact.
- common variable; non familial, failure of B cell maturation
- X linked agammagiardia.
- Ig A def. giardia, allergic, autoimmune dis, fatal transfusion react.
Combined B & T def;
- severe combined immune def.; AR.
- ataxia telangectasia; AR, ataxia, telangiectasia, malignancy, cell mediated im,Ig A.
- Wischott Aldriech; XLR, CMI, IgM, thrombocytopenia, eczema, malignancy.
Acquired;
Causes of neutropenia
Causes of acquired hypogammaglob (B cells)
- synthesis; malnutrition, uremia, viral infection, immunosupp
drugs.
- catabolic dis; thyrotoxicosis, myotonia.
- lost; prot loosing enteropathy, nephrotic S, ovarian
hyperstimulation.
- lymphoproliferative dis; CLL, NHL, MM.
Causes of acquired CMI def (T cells)
- alcohol
- drugs; cyclosporin, cyclophosphamide, steroids.
- lymphomas,
- AIDS,
- medical dis; DM, RA.
 Vaccination
Passive; (Ig)
- used for post exposure, immunocompromized.
- HAV, HBV, ZIG, DT, Rabies, Botulinum.

Active;
1. Subunit vaccines;
- used for patients with CRF, before splenectomy, hypocomplementimics.
- e.g. pneumoccoccal, Meningeococcal, H influenza, HBV
2. Killed;
- used for patients with chronic illness.
- e.g. pertussis, TAB, influenza, cholera.
3. Live attenuated;
- used for healthy individual.
- contraindicated for HIV, patients taking steroids 40mg/d for one week or
long term smaller dose .
- given after ;
3 wks of another live v. 3 m of Ig or stopping steroids , 6 mths from
chemo.
- BCG, Yellow fever, MMR, oral polio.
Genetics
Prokaryotes(microorganisms)
circular DNA,
no nuclear membrane .
Eukaryotes (higher
organisms) have multiple
chromosomes , nuclear
membranes.

Histones allow DNA to twirl

round it to form stable
nucleoprotein complexes.
 The human karyotype Chromosomes
consists of 22 pairs of
autosomes and 1 pair of
sex chromosomes totalling
23 pairs altogether.
Telomeres are DNA
sequence at distal
extremities of chromosomal
arms, become progressively
shorter with each cell
division when it is reduced
to a critical length, the cell is
not capable of dividing.
The enzyme telomerase
lengthen it.
centromeres provide a
point of attachment for the
mitotic spindle.
Lyonization is the process whereby in a cell containing > 1
x chr, only one is active. A Barr body is an inactivated X
chromosome.
Haploid= cell with 23 chromosome as gametes.
Diploid= cell with 46 chromosome
Triploid= cell with 3 copies of each chr.
Aneupoid= contain a number of chr not a multiple of 23.
- Bases are paired with
hydrogen bonds
- In DNA;
- Deoxyribose sugar
- A+T by 2 H bonds
- G + C by 3 H bonds

In RNA,
- uracil instead of thymine
- Ribose
- Single-stranded.
 Cell cycle:

G1 phase ; enzymes for the production of RNA and protein, are produced.
S phase ; DNA is synthesized by replication of the existing strand.
G2 phase ; RNA and protein are synthesized.
M phase mitosis occur:
Cell division results in 2 daughter cells, each of which can
enter its own G1 phase
become an inactive resting (G0) or
die (cell loss fraction).
cyclins= are proteins key regulators of cell
cycles which can bind to enzymes known as
cyclin dependent kinases. These regulate the
progression of the cell cycle.
 Stages of
Mitosis

Prophase:
chromosomes condense
Metaphase:
chromosomes are lined up on cell equator,
attached to the spindle at the centromeres
Anaphase:
centromeres divide.
the chromosomes are pulled to opposite poles by the spindle.
Telophase:
cytoplasm divided into 2 separate cells
 Chromozomal aneuploidy
Turner S (45,X0);
-1:2500 live birth females.
- Streak ovaries, E, failure of menstruation, 2ry sexual ccc
- short stature, normal intelligence.
- Associations;
- CVS; coarctation
- renal; hoarseshoe, agenesis, double ureter.
Kleinfelter;47; XXY
- Hypergonadotrophic hypogonadism
- Male, tall stature.
- Azospermia, testosterone, Gn.
- Gynecomastia, male breast cancer.
- normal intelligence.
 Down syndrome (trisomy 21)
- 2ry to non dysjunction during oogenesis (with increasing
maternal age)
- 5% Translocation bet. Chr 14 & 21.
- 3% mosaism.
- Complication;
- CVS; VSD
- hematologic malig; ALL, AML.
- Alzeheimer disease.
- Duodenal atresia (Double bubble sign), hirshsprung.
 Edwards (trisomy 18);
- overlapping fingers
- renal abn
- CHD
- MR
- diaphragmatic hernia
-mortality early infancy.

Patau S (trisomy 13);

- CNS,
-scalp defect, microphthalmia, cleft lip & palate.
Genome
= DNA. Only about 5% of DNA codes for proteins.
Human genome = 30.000 gene.
Each cell express 16.000 gene.
Housekeeping genes =genes expressed in all cells to provide basic
function for cell survival (constitutive).
Southern blotting detects DNA.

Transcriptome
= m RNA.
Microarray analysis of transcriptome identify the expressed genes.
Northern blotting detects RNA

Proteome
= protein.
Analysis of the proteome is better as it detects changes at the protein
level, not reflected at transcriptome level dt Post translation
processing.(bioinformatics).
Western blotting can be used to detect and quantify proteins
 Gene
3
5
RNA polymerase ex in ex in
binding site

Transforming factor TATA ATG

binding sites box Translation
Translation
termination code
Starting site
Promotor elements

Coding sequences (exons) are interspersed with introns.

Both coding (exons) and non coding regions (introns) exist on RNA.
 Exons= segment of the gene transcripted into m RNA then translated into
proteins.
Introns= segment of the gene transcripted then removed by splicing (not
translated).
Promotor elements = binding sites for initiation of transcription complex at
5.
TF can activate any gene that has a TATA box.
TATA box=
- a promotor element.
- at 25-30 base pairs from the start of transcription.
- anchor to RNA polymerase II.
Enhancers=
- present at 5 or 3.
- not obligatory for initiation.
- but gene expression.
TF;
- basal = constitutive - Housekeeping genes.
- inducible = temporal, spatial expression of genes for tissue phenotype.
Application of TF;
1- many cong malformation are dt inherited mutation of TF.
2- can be oncogenic e.g. CMyC, P53.
3- steroids affect TF.
 Process of protein synthesis
DNA is transcribed into RNA by mRNA polymerase II
mRNA is translated into proteins in the cytoplasm at
the ribosomes.
mRNA contain codon which bind to anticodons on
tRNA.
Transfer RNA (tRNA) is a small RNA chain that has
sites for amino-acid attachment & transfers a specific
amino acid to the growing polypeptide chain according
to the RNA codon.
the anticodon region of tRNA, contains the
complementary bases to the ones encountered on the
mRNA.
Reverse transcription involves transcription of
RNA to DNA (used by retroviruses).
Restriction enzymes cut DNA at nucleotide
sequences specific to each restriction
enzyme.
DNA ligase and polymerase are involved in
joining and linking DNA together.
Plasmids are circular molecules of bacterial
DNA separate from the bacterial chromosome.
 DNA analysis
Direct testing;
= identify abnormality within a well known
specific gene.
- PCR
- restriction enzymes digestion
- Southern blotting

Indirect testing; (linkage analysis)

used when the gene in question has not
been identified before. It involves tracing
DNA markers in more than generation within
a family.

PCR
Def; it is an amplification reaction in which a small amount of target
DNA (template) is amplified to produce enough amount to perform
analysis.
PCR is powerful (need only one copy).
Uses=
1. Detect viral or bact DNA.
2. Detect mutations.

NB; In PCR, two primers are required for a start and stop sequence to
amplify the DNA strand.
DNA polymerase needs to be stable at high temperatures and hence
thermostable enzyme from T. aquaticus is used. The mixture is
heated to below 100C.
DNA polymerase causes synthesis of DNA between two primers
Stages;
1. Mix the specimen with 2 primers & Taq polymerase (thermostable
DNA polymerase).
2. Heat & cool primer anneal to template.
3. Heat ( 72 c) polymerization.
4. Repeat & analyse.
 southern blot; electrophoresis of DNA fragment through gel
solid memb as nitrocellulose+ labelled probe
visualised under x ray film.
Northern blot is a mean to detect RNA (uracil instead of
thymine in m RNA).
Somatic cell hybridization;
- method for gene maping.
- using 2 diff species, chr from 1 species is selectively lost
resulting in clones of certain chr of the another species.
FISH; fluorescence in situ hybridization, labeled probes are
hybridized to chromosomes, and the hybridized probes are
detected with fluorochromes. visualised under florescent
microscope, This technique is a rapid and sensitive means
of detecting recurring numerical and structural
abnormalities. for microdeletions & trisomy.
SSCP (single strand conformation polymorphism analysis); is
a technique for detecting variation in DNA sequence by
running single stranded DNA fragments through a non
denaturating gel.
 Gene mutations;
- mismatch = change in the nucleotide.
- inversion= nucleotide base removed,
reverse directed & reinserted.
- point mutation; single base pair substitution.
 Dominant vs. Recessive
A dominant allele is expressed even if it is
paired with a recessive allele.
A recessive allele is only visible when
paired with another recessive allele.
Recessive alleles are not expressed in the
presence of a dominant allele

43
 Expression
Homozygous
Both alleles alike
AA or aa
Heterozygous
Alleles are different
Aa
Codominant
Two different alleles are both dominant
A = allele for type A blood
B = allele for type B blood
AB = results in type AB blood
 Autosomal dominant
Musculoskeletal; achondroplasia, Ehlers-Danlos syndrome,
Marfan's syndrome , osteogenesis imperfecta
Neuro; Huntington's disease, neurofibromatosis, tuberous
sclerosis, AIP, benign essential tremors.
GIT; intestinal polyposis, Peutz Jeghers syndrome,
Gilbert's disease, hereditary haemorrhagic telangiectasia
Blood; protein C , antithrombin III deficiency, Von
Willebrand's disease, elliptocysis, spherocytosis, C1
esterase inhibitor deficiency
CVS; Familial hypercholesterolaemia
idiopathic hypoparathyroidism
polycystic kidney disease (adult)
Noonan S
Marfan's syndrome
AD
associated with;
1. ocular abnormalities ; upwards lens dislocation
and retinal detachment.
2. Aortic regurgitation due to aneurysmal
dilatation, MVP.
3. Upper to lower body ratio is decreased ,
arachnodactyly, high arched palate.
4. Spontanoeus pneumothorax.
As if a male Turner
 Autosomal recessive
Metabolic; alkaptonuria, galactosaemia, glycogen storage disease ,
homocystinuria, phenylketonuria, mucopolysaccharidoses except
Hunter, oculocutaneous albinism, G6 phosphatase dedficiency (Von
gierkes),
Liver; crigler, DJS, Rotor, hemochromatosis, Wilson's disease,
Gaucher's disease
Blood; B thalathemia, Fanconi anemia, Sickle cell disease, pyruvate
kinase def.
Neuro; ataxia telangiectasia, spinal ms atrophy,
Renal; Bartter's syndrome,
Endocrine; congenital adrenal hyperplasia ,
endemic goitrous cretinism
cystic fibrosis
xeroderma pigmentosa
 Most metabolic disorders are AR except;
1. XLR; MPS 2 (Hunter), G6PD def ,
adrenoleuckodystrophy.

2. AD; AIP, Familial hypercholesterolaemia

 X linked recessive
The features of X linked inheritance;
Males are all affected
Females only occasionally show mild signs of disease
Each son of a carrier a 1:2 chance of being affected
Each daughter of a carrier has a 1:2 risk of being a
carrier
Daughters of affected males will all be carriers
Sons of affected males will not be affected

Renal; Alport, Fabrys disease

Neuro; Beckers, Duchennes muscular dystrophy
Bl; G6PD deficiency, haemophilia A and B
Endocrine; Testicular feminisation syndrome.
Eye; ocular albinism, red-green colour blindness
Hunters syndrome, leishnehan, Wiskott Aldrich syndrome
 X linked dominant (rare)

Daughters of affected males will all be

affected.
All offsprings of an affected female have a
50% chance of being affected.
e.g.
X linked Hypophosphataemic VDR rickets .
Fragile X syndrome
Fragile X syndrome
XLD
delayed mental and motor development
seizures.
prognathism, long face, high arched palate,
large ears, cryptorchidism, hypotonia and
mitral valve prolapse.
 Codominant inheritance
Two different versions (alleles) of a gene
can be expressed, and each version makes
a slightly different protein.
E.g. ABO locus

53
Non Mendelian inheritance;
Polygenic; 2 or more genes influence
phenotype.
Multifactorial; gene + enviroment e.g. DM, HTN,
obesity, CAD, schizophrenia, parkinson,
Alzeheimer.
Mitochondrial inheritance.
Genomic imprinting
 mitochondrial inheritance

Mitochondria contain certain genes & are exclusively

maternally inherited (from oval cytoplasm).
Mitochondrial DNA codes for proteins in the oxidative
phosphorylation .
In Mitochondrial Diseases , all offsprings of affected women
but no offsprings of affected men.
Kearn Sayre's
MELAS (mitochondrial encephalopathy, lactic acidosis,
stroke)
MERRF (myoclonic epilepsy, ragged red fibres)
progressive external opthalmoplegia
Leber's optic atrophy
Genomic imprinting refers to the difference
in phenotypic presentation depending on
the origin of the diseased chromosome
from either maternal or paternal.
Conditions with genomic imprinting:
Albright hereditary osteodystrophy
Prader Willi syndrome
Angelman syndrome
 Trinucleotide repeat
Affected pts has increased number of repeated units
of 3 nucleotides in affected gene (expansion),
become more severe over successive generations
(anticipation).
Myotonic dystrophy (AD)
Huntington dis (AD)
Fragile X S (XLR)
Freidreich ataxia (AR)
Spinocerebellar ataxia (AD)
Anticipation refers to increase in the number of
trinucleotide repeats
 Enzyme deficiencies

Gauchers disease Glucocerebrosidase

deficiency
Niemann Pick disease - Sphingomyelinase
deficiency
Alkaptonuria homogentisic acid oxidase
Homocystinuria cystathionine B synthase.
 Ochronosis;
(Alkaptinuria)
AR
Dt deficiency of homogentisic acid oxidase
accumulation of homogentisic acidpolymerize
to alkapton deposit in different tissues.
C/P; pigmentation of ear, arthritis, intervertebral
disc calcification, dark sweat-stained clothes,
urine darken on standing,renal stone, ocular
comp.
TTT; symptomatic non specific.
cong hyperhomocysteinemia
AR
Reduced activity of cystathionine synthase.
accumulation of homocysteine & methionine.
C/P; Marfanoid + Mental Ret. + thrombosis
( downward dislocation of the lens, high arched
palate, Osteoporosis , livido reticularis,
atherogenic, thrombogenic).
Diagnosis; Na cyanide/nitroprusside test
Ttt; vit B6, B12, folic acid, methionine
restriction, cystine supplemented diet.
 D penicillamine uses;
RA, scleroderma
Cystinurea
wilson

COAL

-Hexagonal crystals in urine analysis

-Colorimetric qualitative test with Na cyanide/nitroprusside test
-quantitative
Liver transplantation before renal
Fabry's disease is an X-linked lysosomal storage
disorder. It is caused by a deficiency of alpha-
galactosidase A. Ceramide accumulation occurs
in various organs including the heart, skin and
nerves. The skin lesion is known as
angiokeratoma corporis diffusum.
Gaucher's disease is associated with the enzyme
glucocerebrosidase. As a result,
glucocerebroside accumulates, principally in the
phagocytic cells of the body but also sometimes
in the central nervous system neurones.
Molecular
 Apoptosis
Def; is the morphological changes that accompagny
the programmed cell death e.g. cell shrinkage,
compaction of chromatin, nuclear & cytoplasmic
apoptotic bodies phagocytosed by MQ, laddering of
DNA on electrophoresis gel by activation of
intracellular nucleases.
programmed cell death= naturally occurring cell
death dt activation of a set of genes in response to
ext signals e.g. from neighbour or extracellular
matrix.
 P53 +

Fas, CD 95 + _
Signals for cell death bcl2
+
TF
+

caspases

endonucleases
 Cancer resists apoptosis by;
- Mutation of P53.
- Causing apoptosis of cytotoxic T cells
(TNF like + Fas).
- Over-expression of Bcl2.
 Apoptosis;
- non-inflammatory process.
- no proteolytic enzymes.
- no free radicals.
- no damage of neighbouring cells.
E.g.
apopt of finger web, selection of neurons ( normal apopt in embrio).
- apopt of excess or autoreactive T lymphocytes ( normal apopt in adult).
- neurodegenerative dis, HIV (dis).
- insufficient apoptosis e.g. cancer, autoimmune dis, viral dis.
Factors that + apoptosis; P53, P27, Fas or CD95 (receptor for TNF),
withdrawal of GF.
Factors that - apoptosis; bcl2 (survival signals), B catenin accumulation
adenoma.
Apoptosis occur through proteases called caspases (e.g. ICE= IL-1B
converting enzyme) that + endonuleases.
Caspases = cysteine aspartate specific proteases.
 Molecular pathogenesis of cancer
Oncogenes
Proto-oncogenes and oncogenes encode growth factors. A single
aa mutation is enough to change the proto-oncogene into an
oncogene.
Mutated proto-oncogenes that cause cancer are called oncogenes.
Examples of oncogenes are:
Ras is the commonest oncogene is involved in sporadic tumours
(colon and lung) and rhabdomyosarcomas.
c-myc translocation occurs in Burkitt's lymphoma.
N-myc proto-oncogene is seen in neuroblastoma.
SRC oncogene is associated with sarcoma.
Mutations of protein kinasesTF (Fos & Jun)+ Myc tumor.
Philadelphia chr bcr + abl (9;22) fusion protein tumor growth.
Bcl-2 inhibits apoptosis, preventing p53 mediated cell destruction
and prevent cell death.
Fas ligands and caspases trigger apoptosis. Bax, Bad and Bak are
members of the oncogenes which promote cell death (of immune
cell).
Tumour suppressor genes ;
NF-1 gene in neurofibromatosis
BRCA-1 in breast and ovarian cancer
Rb gene in retinoblastoma
VHL gene in von Hippel Lindau
P53 Li Fraumeni syndrome
p53 : The p53 Gene is a tumor suppressor gene. If a
person inherits only one functional copy of the p53 gene
from their parents, they are predisposed to cancer and
usually develop several independent tumors in a variety
of tissues in early adulthood. This condition is rare, and
is known as Li-Fraumeni syndrome. Li Fraumeni
syndrome predisposes patients to breast cancer and
sarcoma. p53 is also a transcription factor and is not
found only in malignant cells. It has a role in
downregulating cell division and apoptosis.
P27 Tumor suppressor gene through down regulation of
cell cycle (cyclin dependent kinase inhibitor), if
downregulated sporadic Cancer colon.
 Nitric oxide
(NO)
Endothelial derived relaxation factor
Produced from L arginine by oxidation of Nitrogen NO + citrulin.
C GMP (2ry mess) in neighboring cells.
Produced in;
1. Constitutive..Vascular end & Nervous system VD, sm
hyperplasia, plat agg. new memory.
2. Inducible.. in MQ, PNL, plat, hepatocytecytotoxic.
Clinical application;
- So used as nitrates or inhaled NO in pulm HTN.
- endothelial dysf in DM, HTN, smokers & hypercholestrolemia is dt
loss of NO bioavailability.
- NO in atherosclerosis, HTN dt CRF, HRS, Alzeheimer.
- NO in septic shock, ARDS, acute inflammation.
 Endothelin I (VC)
ET-1 (end, sm, coronary, GIT).
Related to dis;
- HTN, HRS, ARF, CHF, Raynaulds. (VC)
- VC following subarachnoid Hge.
ET1 receptor blockers & CEI used as anti HTN.
Pro-inflammatory cytokines
Il-1, TNF, TGF-B, Heat shock protein, free radicals.

TGF-
action;
- tissue repair.
- extracellular matrix.
- fibrosis.
tissue injury + plat release of TGF-B chemotaxis
monocytes (+ fibroblast GF, TNF, IL-1)
involved in glomerulosclerosis, hep fibrosis, pulm
fibrosis, bleomycin lung.
NB;
 HSPs (Heat shock proteins)
heat, chemicals, free radicals damage of
intracellular proteins HSP cell
resistance to stress through;
- prot folding & unfolding.
- degrad of prot ( by ubiquitination).
dis associated; if mutated cataract, motor
neuron deg.
bact HSP + immune syst.
Free radicals
Any molecule with 1or more unpaired electron (more
reactive); peroxide, super, hydroxyl, NO.
NB; hydroxyl is the most reactive.
action;
- lysosomes.
- lipid peroxidation of memb.
- mutations (by attaching purines & pyrimidine).
Diseases athero, cancer, neurodeg ( MND).
Free radical scavengers;
- tocopherol (Vit E).
- ascorbate (Vit C).
- glutathione.
- Beta carotene.
- Flavenoids.
 Adhesion Molecules
Def; Molecules that interact as receptors & ligand.
4 groups;
- Ig ( CD2, CD3, NCA (neural cell adh), ICAM (intercellular)
bind to LFA ( lymph funct ass)to recruit lymphocytes.
- integrin ( cell to matrix) Integrins are surface receptors by
which cells are attached to extracellular matrix..
- Cadherins (Nerve & Muscle ).
- selectins ( leukocytes to endoth in inflam, over expressed
in autoimmune viral hepatitis, organ rejection).
Clinical application;
1. leuk adhesions deficiency recc bact sepsis.
2. integrin IIb IIIa ( plat receptor to fibrinogen)
deficiency Glansman thrombathenia.
Ab (abciximab) antithrombotic in coronary Ht.
 Stem cells
progenitor cells.
present in certain tissues e.g. BM, embrionic.
embryonic totipotent (any tissue).
BM Bl. cells only, can be recruited by Ag
sorting with CD34 Ab & undergo
transdifferentiation to non hematologic cells.
Physiology
 O2-Hb dissociation curve
is shifted to the right when there is:
- an increase in CO2
- increase in hydrogen ions (fall in pH)
- increase in temperature
- increase in lactate
The curve is shifted to the left by
- increased carboxyhaemoglobin
- methaemoglobin
- fetal haemoglobin.
 Receptors
A) Cell membrane surface receptors;

1- ligand gated Ion channel;

- e.g. neurotransmitter open ion channel
- Nicotinic Na.
- GABA, Glycine Cl.
2- receptors with protein tyrosine kinase
- phosphorylation of tyrosine residue of receptors cascade of
cytoplasmic prot.
e.g. insulin, PDGF, prolactin, IGF1, MQ CSF, NGF, EGF.
3- G protein coupled
- is a protein that bind to guanine nucleotide).
- G protein receptors are 7 transmembrane spanning receptors.
- Examples are: Muscarinic Ach receptor, Adrenergic receptor
(adrenaline), Retinal rhodopsin receptor, FSH, TSH, ACTH,GABA
- Dis associated with G protein abn e.g. cholera, Albright HOD, MeCune
Albright S, pit adenoma.
NB; prot kinases add phosphate group to serine, threonine, tyrosine residue
(# phosphatase)
B) Intracellular receptors;
- cytoplasmic= steroids.
- Nuclear= thyroid.
- no 2 ry mess.
- intracytoplasmic receptors.
- the complex travel to the nucleus &
bind to hormone responsive elements.
Stimulation of receptors leads to:
- Vasoconstriction
- decrease in gut motility
- uterus contraction
- decrease in pancreatic exocrine secretion

Cholera toxin: activates G protein, which

activates adenylate cyclase. Elevated
cAMP results in unrestricted chloride
secretion from villous crypts.
 GIT
Stomach;
- 3 litres HCL
- parietal cell HCL, intrinsic factor
- chief cell pepsin
- surface cells mucous, HCO3.
- parasymp & symp via Meissner, Aurbach
plexus.
- Bl sully celiac trunk.
H pylori
 H pylori
Campylobacter pyloridis, is a gram-negative microaerophilic rod
Pathologic mech;
1. produce urease. Urease produces ammonia from urea, an essential step
in alkalinizing the surrounding pH epithelial damage.
2. Produce protease, lipase damage of mucosal gel.
3. Increase HCl directly or indirectly through cytokines on G, D, parietal cells
resulting in gastrin & somatostatin.
4. Chemotactic factors PNL.

Incidence; 80% in developing countries, 20% in industrialized.

Complications;
1. Chronic active gastritis.
2. PUD
3. MALT lymphomas
4. Adenocarcinoma
5. Extragastric; IsHD, enteropathic arthropathy, hep enceph, acne rosesea,
alopecia, urticaria, Raynaulds.
 Gut Hormones
Gastrin;
- is secreted by the G cells of gastric antrum.
- It stimulates parietal cells produce hydrochloric acid.
- Its production is stimulated by;
- gastric distension, certain aa (phenylalanine, tryptophan).
HCL.
- vagal stimulation
- S.Ca
- epinephrine.
- Its production is inhibited by;
- HCL
- secretin, GIP, VIP
- glucagon, calcitonin
- effects; gastric motility & secretion
mucosal growth
pancreatic secretion; insulin, glucagon, bicarbonate.
 Cholecystokinin.
- is produced by the duodenum & jejunum.
- Its production is stimulated by fat, aa, peptides.
- stimulates GB contraction, pancreatic enzyme secretion, delay
gastric empting.

Secretin ;
- is produced by the jejunum.
- Its production is stimulated by HCL
- stimulates pancreatic enzyme secretion(HCO3).
- It relaxes the oesophageal sphincter , delay gastric empting.

Motilin;
- is produced by the duodenum & jejunum.
- Its production is stimulated by acid
- increase motility.
 Vasoactive intestinal peptide (VIP)
- is produced by SI
- Its production is under neural stimulation
- promotes intestinal & pancreatic water and electrolyte secretion.

Gastric inhibitory peptide;

- produced by duodenum & jej.
- Its production is stimulated by glucose, fat &aa
- inhibit gastric acid secretion, stimulate insulin secretion, motility.

Somatostatin;
- produced by D cells of pancreas.
- stimulated by vagal & B adrenergic stimulation.
- stimulate gastric empting & inhibit everything else (gastric & panc
secretion).

Pancreatic polypeptide;
- produced by PP cells in pancreas.
- stimulated by protein rich diet
- inhibit pancreatic & biliary secretion.
 Q
The following statements regarding gastrointestinal hormones are
correct:
A gastrin increases gastric motility.
B somatostatin decreases gastric motility.
C pancreatic polypeptide stimulates pancreatic bicarbonate
secretion.
D enteroglucagon decreases the small bowel transit time.
E secretin maintains mucosal growth.
True= abd
Comments:
Pancreatic Polypeptide inhibits exocrine pancreatic secretions.
Secretin is important in stimulating pancreatic secretion. The role of
enteroglucagon is not well defined but includes villous hypertrophy
and hence reduction in transit time. Somatostatin inhibits many
many GI functions including gastric motility.
 Vitamins deficiencies
Nutrient Clinical Finding Contributing Factors to
Deficiency
Vitamin A Xerophthalmia, nightblindness, Bitot's Fat malabsorption,
spots, follicular hyperkeratosis, impaired infection, measles,
embryonic development, immune alcoholism, protein-
dysfunction energy malnutrition
Vitamin D Rickets: skeletal deformation, rachitic Aging, lack of sunlight
rosary, bowed legs; osteomalacia exposure, fat
malabsorption, deeply
pigmented skin
Vitamin E Peripheral neuropathy, spinocerebellar Occurs only with fat
ataxia, skeletal muscle atrophy, retinopathy malabsorption, or
genetic abnormalities of
vitamin E
metabolism/transport
Vitamin K Elevated prothrombin time, bleeding Fat malabsorption, liver
disease, antibiotic use
Nutrient Clinical Finding Contributing Factors to
Deficiency
Thiamine Beriberi: neuropathy, muscle weakness and wasting, Alcoholism, chronic diuretic
cardiomegaly, edema, ophthalmoplegia, confabulation use, hyperemesis
Riboflavin Magenta tongue, angular stomatitis, seborrhea,
cheilosis
Niacin Pellagra: pigmented rash of sun-exposed areas, bright Alcoholism,
red tongue, diarrhea, apathy, memory loss, vitamin B 6deficiency,
disorientation riboflavin deficiency,
tryptophan deficiency
Vitamin B6 Seborrhea, glossitis convulsions, neuropathy, Alcoholism, isoniazid
depression, confusion, microcytic anemia
Folate Megaloblastic anemia, atrophic glossitis, Alcoholism, sulfasalazine,
depression ,homocysteine pyrimethamine, triamterene
Vitamin B12 Megaloblastic anemia, loss of vibratory and position Gastric atrophy (pernicious
sense, abnormal gait, dementia, impotence, loss of anemia),
bladder and bowel terminal ileal disease,
control, homocysteine ,methylmalonic acid strict vegetarianism, acid
reducing drugs (e.g., H 2
blockers)
Vitamin C Scurvy: petechiae, ecchymosis, coiled hairs, inflamed Smoking, alcoholism
and bleeding gums, joint effusion, poor wound
healing, fatigue
Element Deficiency
Calcium Reduced bone mass, osteoporosis
Copper Anemia, growth retardation, defective
keratinization and pigmentation of hair,
hypothermia, degenerative changes in aortic
elastin, osteopenia, mental deterioration
Fluoride Dental caries
Iodine Thyroid enlargement ,cretinism
Iron kilonychia, pica, anemia,, impaired cognitive
development,
Manganese Impaired growth and skeletal development,
reproduction, lipid and carbohydrate
metabolism; upper body rash
Selenium Cardiomyopathy, heart failure, striated muscle
degeneration
Phosphorou osteomalacia, proximal muscle weakness,
s rhabdomyolysis, paresthesia, ataxia, seizure,
confusion, heart failure, hemolysis, acidosis
Zinc Growth retardation, taste and smell, alopecia,
dermatitis, diarrhea, immune dysfunction,
gonadal atrophy, congenital malformations
Toxicity
Renal insufficiency (milk-alkalai syndrome),
nephrolithiasis, impaired iron absorption
Nausea, vomiting, diarrhea, hepatic failure,
tremor, mental deterioration, hemolytic anemia,
renal dysfunction
Dental and skeletal fluorosis, osteosclerosis
Thyroid dysfunction, acne-like eruptions
Gastrointestinal effects (nausea, vomiting,
diarrhea, constipation), iron overload with
organ damage, acute systemic toxicity
Neurotoxicity, Parkinson-like symptoms
Encephalitis-like syndrome, Parkinson-like
syndrome, psychosis, pneumoconiosis
Alopecia, nausea, vomiting, abnormal nails,
emotional lability, peripheral neuropathy,
lassitude, garlic odor to breath, dermatitis
Lung and nasal carcinomas, liver necrosis,
pulmonary inflammation
Hyperphosphatemia
Reduced copper absorption, gastritis,
sweating, fever, nausea, vomiting, Respiratory
distress, pulmonary fibrosis
 Iron is absorbed in upper small intestine.
Iron absorption is increased with ascorbic
acid. The sulfate form contains more
elemental iron per dosage unit than
gluconate.
 Q
The following may be found in the event of
a prolonged bout of vomiting except
A tetany
B hypochlorhydria
C megaloblastic anaemia
D hypokalaemia
E high serum aldosterone .
C
Renal physiology
The glomerular filtration barrier;
1. Fenestrated endothelial cells.
2. Glom BM
3. Visceral epith cells (podocytes) & filtration slit diaphragm.

GBM is composed of 3, 4, 5 type IV collagen.

Juxta glomerular apparatus;

1. Modified aff arteriolar cells.
2. Macula densa in DCT
3. Lacis cells in extraglom. Mesangium.

Stimuli for renin secretion;

1. RBF Na delivery to the macula densa
2. BP (baroreceptor mech) renin from aff cells.
3. B adrenergic stimulation.
 Renin catalyse the conversion of angiotensinogen into
Ang I.

Angiotensin II;
- thirst sensation
- systemic VC
- VC of efferent arteriole mainly GFR.
- stimulate aldosterone secretion
- stimulate ADH
- direct stimulation of Na reabsorption from PCT by
stimulation of Na/H exchanger.

Andosterone;
- stimulate Na-K ATPase,
- luminal memb permeab to K
- H secretion by collecting duct
ADH;
Stimulated by plasma osmolarity > 285,
plasma volume.
V1 receptor VC
V2 water permeability in the collecting ducts
by stimulation of adenylate cyclase
CAMPStimulate memb fusion of vesicle
containing water channels.

ANP;
Inhibit Na reab in the collecting duct
GFR
Inhibit ADH & Ald secretion
 Tubular function
PCT;
- Absorption of all glucose, aa.
- 90% of HCO3
- 60% Na, Cl, K, Ca
- Phophate absorption inhibitesd by PTH.

LOH;
- countercurrent multiplier (NaK2Cl in thick ascending limb) #
frusemide.
- 70% of Mg absorption

DCT; Na/Cl cotransport # thiazide.

CD;
principle cells amiloride sensitive channels
aldosterone on NaK ATPase
ADH on aquaporins
intercalated cells H or HCO3 secretion
 In pre renal failure / Acute Tubular
Necrosis (hypovolaemia, dehydration),
the kidney attempts to retain sodium,
hence urine sodium is <20mmol/l.
The anion gap is normal (Na + K - Cl -
Bicarb) - normal range is 10 - 16.
Serum osmolality is estimated by the
formula : [2 (Na) + urea + glucose].
 Sweat chloride test
False +ve conc of sweat electrolytes;
1. Endocrine; hypo-adrenal, parath, thyr,
cong nephr DI.
2. Metabolic; G6PD, MPS
3. Ectodermal dysplasia, familial
cholestasis, pancreatitis, malnutrition.

False ve; nephrotic S.

 Q
Atrial natriuretic peptide
A inhibits distal tubular reabsorption of sodium
B promotes excretion of potassium in the urine
C levels in the blood are independent of left
ventricular function
D inhibits vasoconstriction mediated by
angiotensin II
E is a vasodilator without causing reflex
tachycardia
 Neuro
Myosin is involved in striated muscle
contraction. It forms filaments in a
hexameric array of 2 heavy chains and 2
pairs of light chains.
Myosin heavy chain mutation is implicated
in familial hypertrophic cardiomyopathy.
HOCM and Carney complex are forms of
myosin chain disorders.
 Weakness of small ms of the
hand;

- lower trunk of Br plexus injury all

small ms of the hand (T1) + long
flex & ext of fingers (C8).

- T1 root e.g. cervical rib, pancoat,

sub art aneurysm. all small ms of
the hand.

- ulnar n all small ms of the hand

except 2 lateral lumbricals & thenar
group (T1 through median n).
Dermatomes
 Cord compression
Upper 4 cervical;
- neck pain
- quadriplegia, wasting UL.
- cr n 5 spinal root; dissociated sensory loss of face.

C5,6;
- pain in shoulder, outer arm, FA, thumb
- wasting of romboids, deltoid, biceps, supinator, brakioradialis.
- lost biceps, exagerated triceps, inverted supinator reflexes.

C8,T1;
- pain medial side
- wasting of flexors of wrist, hand.
- horner

L3,4;
- medial side of LL pain.
- wasting of quadriceps, abductors
- lost knee, extensor planter reflexes.
 Epiconus= L4,5, S1,2 segments of SC.
lesions;
- lost anckle, preserved knee reflexes
- motor;extension of hip, flexor of knee, dorsi & planter flexion of foot,
toes.
- sensory; most of leg
- micturition disturbance.

Conus medullaris= S3,4,5 segments of SC.

lesions;
- no motor or sensory of LL.
- dissociated sensory loss of saddle area.
- early urinary incontinence.
- impotence.

Cauda equina= all lumbar & sacral roots.

lesions;
- early radical pain.
- sphincters late (retension then autonomic)
- LMNL in LL.

NB; siatica= roots of epiconus (L4,5, S1,2,3)

 Root compression
C5; deltoid
C6; biceps & brakioradialis
C7; wrist extensor, triceps
C8; finger flexors, thumb abductors
T1; small ms of the hand
L1,2; iliopsoas (flexion of hip)
L3; quadriceps (knee exten
L4; ant. Tibial (dorsiflexion & inversion)
L5; ant. Tibial & glutei.
S1; calf ms, glutei
S2; hamstring
S3-5; saddle area.

Biceps reflexes= C5,6

Triceps reflexes; C7,8
Supinator reflexes;C6
Knee reflexes L3,4
Anckle reflexes; S1,2.
 Symptoms Ppitating Acts Examination
Carpal Numbness, pain Sleep or repetitive - Sensory loss in thumb, 2nd,3rd
tunnel or paresthesias in hand activity fingers
syndrome fingers - Weakness in thenar muscles;
-Tinel and Phalen signs
Ulnar nerve Numbness or Elbow flexion Sensory loss in the little finger
entrapment paresthesias in during sleep; and ulnar half of ring finger
at the elbow ulnar aspect of elbow resting on Weakness of the interossei and
hand desk thumb adductor; claw-hand
Ulnar nerve Numbness or Unusual hand Like UNE but sensory
entrapment weakness in the activities with examination spares dorsum of
at the wrist ulnar distribution tools, bicycling the hand, and selected hand
in the hand muscles affected
Radial Wrist drop Sleeping on arm Wrist drop with sparing of elbow
neuropathy after inebriation extension (triceps sparing);
at the spiral with alcohol finger and thumb extensors
groove "Saturday night paralyzed; sensory loss in radial
palsy" region of wrist
Thoracic Numbness, Lifting heavy Sensory loss resembles ulnar
outlet paresthesias in objects with the nerve and motor loss resembles
syndrome medial arm, hand median nerve
forearm, hand,
and fingers
 Symptoms Precipitating Examination
Activities
Femoral Buckling of knee, Abdominal Wasting and weakness of
neuropathy numbness or hysterectomy; quadriceps; absent knee jerk;
tingling in lithotomy position; sensory loss in medial thigh and
thigh/medial leg hematoma, DM lower leg
Obturator Weakness of the Stretch during hip Weakness of hip adductors;
neuropathy leg, thigh surgery; pelvic sensory loss in upper medial
numbness fracture; childbirth thigh
Meralgia Pain or numbness - Standing /walking Sensory loss in the pocket of the
paresthetica in the anterior -Recent weight pant distribution
lateral thigh gain
Peroneal n. Foot drop Usually an acute Weak dorsiflexion, eversion of
entrapment compressive the foot
at the fibular episode Sensory loss in the anterolateral
head identifiable; wt loss leg and dorsum of the foot
Sciatic Flail foot and Injection injury; Weakness of hamstring, plantar
neuropathy numbness in foot fracture/dislocation and dorsiflexion of foot; sensory
/ prolonged loss in tibial and peroneal nerve
pressure on hip distribution
(comatose patient)
 Q
A lesion of the facial nerve in the internal auditory meatus will affect
A taste
B sensation over cheek
C lacrimation
D sweating over cheek
E blinking
True=ace
Comments:
The extent of dysfunction depends on the level of injury. If it is proximal to
geniculate ganglion eg internal auditory meatus, taste is lost in the anterior
2/3 of tongue. Also secretion from submandibular, sublingual and lacrimal
glands is impaired. Hyperacusis is due to paralysis of stapedius. Orbicularis
oculi is affected causing inability to blink/close eyelids. Sensation over face
supplied by trigeminal nerve, and sweat glands controlled by sympathetic
nervous system eg anhydriosis in Horner's syndrome.
 Q
The following associations of muscles and
nerve supply are true except
A triceps and C7
B deltoid and C5
C gastroenemius and S1
D quadriceps and L3
E long flexors of fingers and C6
E
Comments:
Finger flexors and extensors are supplied by C8.
 Q
The following are true of lipoprotein metabolism:
A Large LDL particles are most atherogenic
B LDL concentrations can be calculated from total cholesterol,
triglyceride and HDL concentrations
C VLDL is secreted by the liver
D hyperchylomicronaemia may cause pancreatitis
E dietary lipid is absorbed into the blood as chylomicrons
The true= bcd
Comments:
LDL concentrations can be calculated from HDL, total cholesterol and
triglyceride using the Friedwald equation. Small, high density LDL
particles are the most atherogenic. Cholesterol and triglycerides that
are absorbed from the gut are transported on chylomicrons into the
blood through the lymphatic system and thoracic duct.
Hyperchylomicronaemia, associated with type I hyperlipidaemia is
rare and is associated with hypertriglyceridaemia and pancreatitis.
VLDL is secreted by the liver.
Causes of Retinitis pigmentosa are:
Kearn Sayre's syndrome
Usher's disease
Refsum's disease
Lawrence Moon Biedl syndrome
Alports's syndrome
Friedrich's ataxia