Cell Physiology

Prof Dr Ahmed Kaid Allow

Faculty of Medicine –SU
Yemen
2023

AKA Cell and Transport 1

Cell Physiology

Prof Dr Ahmed Kaid Allow

Faculty of Medicine –SU
Yemen
2023

AKA Cell and Transport 1

Cell Physiology

Prof Dr Ahmed Kaid Allow

Faculty of Medicine –SU
Yemen
2023

AKA Cell and Transport 1

AKA Cell and Transport 2
 Intended Learning Outcomes (ILOs)– cell physiology

• By the end of the this topic, students should be able to

• Describe the basic structure and function of the cell as the functional unit of the body.
• Discuss the basic structure and functions of each of the following:
• The cell (plasma) membrane , the cytosol
• mitochondria and mitochondrial medicine
• smooth and rough endoplasmic reticulum (ER)
• Ribosomes, Golgi apparatus
• Lysosomes ,peroxisomes
• the cytoskeleton, centrioles
• cilia and flagella , the nuclear envelope and nuclear pores
• the chromosomes , the nucleolus

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 Introduction
Cell .... All the living
organisms are consisting
of cells
Life’s home ...... !!!!

Cell is the basic unit of the life

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In the end of these presentations you should be
understand ….

Homeostasis Cell Transport

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Cell to body

1 2 3 4

Cells Tissues Organs Systems

Human Organism

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History of the cell

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Types of Cells:

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 Comparison
of prokaryotes
and
eukaryotes

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 The Eukaryotic Cell
nuclear pores
nucleus DNA
nuclear envelope smooth endoplasmic
nucleolus reticulum
free ribosomes
cytoskeleton cytosol

lysosomes

rough
endoplasmic
reticulum Golgi complex
plasma membrane

transport vesicle
mitochondria
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Cell organization

Cell organized from:

• 1). Water (60-85% TCM).
• 2). Proteins (10-20% TCM).
• 3). Lipids(1-6% TCM).
• 4). Carbohydrates(1-6% TCM).
• 5). Electrolytes < 1%
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Organization of the cell
1. • Membranes
1. Plasma membrane

2. Membrane separates
most other individual
components of the cell
1. Nucleus
2. Organelles
2. Cytoplasm - suspension of
fluid with various cellular elements

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Organization of the membrane
•Membranes: Structurally define cells, nucleus, and organelles.
1. Proteins 55%:
1. Integral protein: Channells and Carriers
2. Peripheral proteins: Enzymes and Receptors
2. Lipids 40%:
1. Phospholipids-
1. Hydrophilic portion of membrane primary “building block” of the membrane-
flexibility of the membrane
2. Fluid; mobile for lipid soluble substances like O2 and CO2

2. Cholesterol
• stiffens membranes
• Can move in any dimension through membrane- permeability
3. Carbohydrate 5%
1. Glycolipids/ Glycoprotein : lipid/sugar moiety
2. Receptors: protein/sugar moiety

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Cell (Plasma) Membrane Danielli and Hugh Davson in 1935

Sandwich model

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Model of Cell Membrane Danielli and Hugh Davson in 1935

Sandwich model

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 1. Cell adhesion proteins and junction
Functions of cell membrane proteins
2. Some carrier (transport) proteins
3. channel proteins (Na-K pump)
1. Function of lipid CM (selective 4. Some hormone receptors Like insulin, GH,
permeability) ABO system, Rh-resus factor
1. Permeable for transport of lipid-soluble 5. Some receptor-enzymes has both
substances… like O2, CO2 and alcohol receptors and enzymatic function
2. The water-soluble substances such as glucose, 6. Channelle-enzymes like transport of ions
urea and electrolytes cannot pass through this actively and passively
layer 7. ATP-ase enzyme
8. Digestive enzymes - GIT
2. Function of proteins CM: Abnormalities of cell membrane ???
1. Integral protein 1. Abnormalities in the gene coding of CM
1. Channels proteins like Cystic fibrosis affect liver
2. Carriers pancreas, lungs which damage its function
2. Peripheral protein 2. Membrane transport defect like Cl- and Na+
1. Enzymes – inner side like cAMP IP etc and and Ca etc
cytoskeleton 3. CM-fluidity like in anormal lipids
2. Receptors – outside like hormones or carrier 4. A lot of hereditary diseases of CM like
deficiency of CM-proteins → spherocytosis
(breakdown of CM of blood cells) etc
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Function of cell membrane cont.
• Carbohydrate:
1. Receptors – Glycoprotein Abnormalities of carbohydrate in the CM:
Receptors or Glycolipids 1. Abnormalities in the cell-communication,
2. Glycocalyx – which is a thin layer adherens, cell signaling, and immune system etc
of CHO with lipid (Glycolpid or e 2. Congenetal disorder of glycosylation-(due to
protein glycoprotein) covering abnormal CHO in the CM) it can cause
the inner side of CM multiorgan failure.
3. Abnormalities in the ABO-blood grouping
system which can lead to hemolytic disorders of
newborn.
4. Cancer like Tumor-associated CHO.
4. Autoimmune disorders like Guillain-Barre
Syndrome and Miller Fisher syndrome.
5. Abnormal CM physiological receptors due to
abnormal CHO
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General function of the cell membrane
• 1. Protective function:- protect cytoplasmic Model of Cell
contents Membrane
• 2. Selective permeability: for lipid-soluble and
water-soluble substances
• 3. Absorptive function: transport function
• 4. Excretory function: exocytosis and CM-
transport
• 5. Exchange of gases: Diffusions and osmosis
• 6. Maintenance of shape and size of the cell:
• 7. Cell-communication, between cells-
receptors
• 8. Cell-signaling – transport of action potential

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 Cytoplasm
• Cytoplasm of the cell is the jellylike
material formed by - Organelles Function
• 80% of water. 1- Endoplasmic Manufacturing of the cell
• 10% proteins and reticulum.
• 5% lipids and 2- Ribosomes. Protein synthesis
• 5% carbohydrates.
3- Mitochondria. Entergy formation
• It contains a clear liquid portion called 4- Lysosomes. Protein-digestive system of the cells
cytosol and various particles of different 5- Peroxysomes. Lipid-digestive system of the cells
shape and size.
6- Golgi apparatus. Quality-control system of the cells
• There are 2 types of cytoplasm 7- Cytoskeleton. Shape formation
• ectoplasm –which is near to inner side of CM
8- Centrosomes. Cell-division system
• endoplasm – true cytoplasm where the
cytoplasmic organelles are functioning

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 Mitochondria Cellular Power Plant
• Unique Characteristics: • Mitochondrial diseases (Mitochondreal
• ATP-production cytoplasmic organ. medicine):
• Self-replicated
• mt-DNA mutation leads to problems in its
• For Aerobic respiration- production of ATP from
glucose or metabolite ATP from FA and AA and functions of mitochondria and nuclear-
oxidative phosphorylation. DNA mutation leads to synthesis of
• Calcium homeostasis: like in cell-signaling, muscle abnormal protein which involved in the
contraction and relaxation, and cell-apoptosis (cell-
death). mitochondrial function.
• Reactive Oxygen Species (ROS), it is a major source of • Energy deficiency diseases: It can affect any organs
ROS: cell signaling, defense, neutralize ROS and and systems of human body for example fatigue,
maintain cellular metabolism
weakness, seizors, ataxia, developmental delay. So it
• Apoptosis regulation: regulation of cell-death; any can affect heart, brain, muscles etc.
abnormalities in this process leads to cancer.
• Inheritance and genetics: mtDNA is solely from mother • mit. Genetic diseases inherited from the mother:
and its mutation can lead to many hereditary diseases Hereditary optic neuropathy →progressive vision
• Because of mtDNA (maternal lineage only) allowing them to
loss); Mitochondrial encephalomyopathy; myoclonic
carry-out certain function independently of the cell. epilepsy; Myopathy; epilepsy; lactic acidosis.
• It covered by Double membrane •
• The inner membrane is heavily folded into "cristae"
• The gel-like fluid "matrix" contains enzymes for production • Diagnosis: clinically including analysis of mt-DNA
of adenosine triphosphate (ATP)
karyotyping.

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‫وكوندريا هي هياكل خلوية ذاتية الحياة )‪ (organelles‬توجد في الخاليا الحيوانية والنباتية‪ .‬لها عدة وظائف مهمة وتأثيرات على العديد من‬
‫العمليات الحيوية في الجسم‪ .‬سأشرح لك بالتفصيل بعض هذه الوظائف‪:‬‬

‫‪ .1‬التنفس الهوائي و إنتاج ال‪ :ATP‬امليتوكوندريا تلعب دوًرا حاسًما في التنفس الخلوي الهوائي‪ ،‬حيث تحدث عملية تحليل الجلوكوز )أو‬
‫ألحماض الدهنية واألحماض األمينية( في داخل امليتوكوندريا إلنتاج الطاقة في شكل جزيئات ‪ .ATP‬يتم ذلك من خالل تفعيل عملية التهيئة‬
‫األكسدة والفسفورة األكسدة )‪.(oxidative phosphorylation‬‬

‫‪ .2‬توازن الكالسيوم‪ :‬امليتوكوندريا تلعب دوًرا في تنظيم توازن الكالسيوم داخل الخلية‪ .‬تستخدم الكالسيوم في عمليات اإلشارة الخلوية‪،‬‬
‫وانقباض واسترخاء العضالت‪ ،‬وتنظيم الخاليا املوتية )االبت ََلْعم(‪.‬‬

‫‪ .3‬الجزيئات النشطة األكسجينية املتفاعلة )‪ :(ROS‬امليتوكوندريا هي مصدر رئيسي للجزيئات النشطة األكسجينية املتفاعلة )‪ .(ROS‬تلعب‬
‫هذه الجزيئات دوًرا في عمليات اإلشارة الخلوية والدفاع الخلوي‪ ،‬وتحييد ‪ ROS‬والحفاظ على التمثيل الغذائي الخلوي‪.‬‬

‫‪ .4‬ضبط الخلية املوتية‪ :‬امليتوكوندريا تلعب دوًرا في ضبط عملية موت الخاليا )االبت ََلْعم(‪ .‬أي اضطرابات في هذه العملية يمكن أن تؤدي إلى‬
‫حدوث أمراض مثل السرطان‪.‬‬

‫‪ .‬التوراث والوراثة‪ :‬الحمض النووي امليتوكوندري )‪ (mtDNA‬ينتقل فقط عبر األم‪ ،‬وتحدث تحورات في ‪ mtDNA‬يمكن أن تؤدي إلى العديد‬
‫من األمراض الوراثية‪.‬‬

‫‪ .6‬األمراض امليتوكوندرية‪ :‬تحدث مشاكل في وظيفة امليتوكوندريا نتيجة لتحورات في ‪ mtDNA‬أو تحورات في الحمض النووي النووي الذي‬
‫يتحكم في توليف البروتينات امليتوكوندرية‪ .‬تتسبب هذه املشاكل في نقص الطاقة ويمكن أن تؤثر على أعضاء وأنظمة الجسم املختلفة‪.‬‬

‫‪ .7‬تشخيص املرض‪ :‬يتم تشخيص األمراضطرابات امليتوكوندريا واألمراض امليتوكوندرية من خالل التقييم السريري وتحليل ‪ .mtDNA‬يمكن‬
‫أي ً‬
‫ضا إجراء تحليل الكاريوتايب ل ‪ mtDNA‬لتحديد التغيرات الهيكلية في الجينوم امليتوكوندري‪.‬‬
 Cellular Recycling of mitochondria

• Contain digestive enzymes

that digest warn-out
organelles and foreign
materials that enter the cell
• Produced by the Golgi
apparatus
• Waste disposal and
recycling

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 For Protein synthesis

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Cell physiology cont…
Endoplasmic Reticulum
 Remember …
Endoplasmic Reticulum

• ER is the major site of protein synthesis.

• Rough and smooth ER and its physiological differences.
• Synthesis and translocation of the polypeptide into the ER occur
simultaneously.
• Relationship between ER and Golgi apparatus and nuclear DNA.
• Secretory proteins:
• translocated freely into interior of the ER
• Move to "smooth" ER section for encapsulation
• Vesicle "pinched off" for secretion, or further
processing at Golgi complex
• Other functions: "smooth" ER contains enzymes for
• Lipid synthesis: lipid and steroidal hormone synthesis
• Detoxifying: endogenous and exogenous toxic substances (esp. liver)
• Calcium storage (muscle; sarcoplasmic reticulum)

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 Golgi Complex
Cellular refining facilities

• Closely related to the ER.

• Composed of many layers like SER.
• Presents in all secretory cells.

Function:

1. Formation of membrane for secretory vesicles

(Packaging).
2. Quality control center of the cell
3. More concentrates the contents of the
secretory vesicles.
4. Finishing process on the secretory vesicles
(Labeling).
5. Production of lysosomes. ????

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Cell physiology cont.
Digestive system of the cell
or [Cellular cleanup crew (system)]
Lysosomes cont…

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 Remember …. Lysosomes
Cellular cleanup crew (system)

Lysosomes
• Membrane-enclosed sacs of hydrolytic enzymes (breakdown of
large proteins, CHO, and lipids into small particles that can be
used again by the cell)
• Remove cellular debris or worn-out organelles through the process
which called autophagy.
• Destroy invading pathogens. Abnormalities of lysosomal
• Remove of unacceptable products of ER. depend on the type of
• Autolysis. enzyme-deficiency or gene-
• It participate in the cell signaling and immune response mutation like
• Phagolysosomes are involved the breakdown of phagocytosis of mucopolysachridoses-group of
bacteria and microbes or viruses. diseases which involve skeletal
• Types of lysosomes: abnormalities, organ
1. Primary lysosomes: derived from Golgi apparatus and involved in the enlargements, neurological
process of lysis of phagocytic digested molecules.
2. Secondary lysosomes are formed from fusion with endocytic vesicles. disorders
3. Autolysosomes is formed from autosomes with autophagosomes which
contain cell membrane like bacteria.
4. Residual bodies-are a lysosomes with undigested molecules
5. Secretory lysosomes: or exocytic lysosomes and specialized for exocytosis
of lysosomes with secretory proteins into the ECF.
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 Cytosol
(cytoplasm and friends)

• Also Cytosol is the site of:

Cytosol:
= semi gelatinous intracellular • Intermediate metabolism and
fluid storage:
Medium for suspension of: • degradation, synthesis, or transformation of
1. Organelles, small organic molecules for fuel.
2. Ions, nutrients, wastes, • Metabolism
enzymes etc.……. • Glycolysis - energy.
3. Inclusions • Process fatty and amino acids for
entry into Krebs cycle
• Storage
• Fat droplets (esp adipose cells)
• Glycogen.
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 "free" ribosomes

ER
Plasma
membrane

microtubule

Intermediate filaments
microfilament
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 Cell physiology cont…
• Cytoskeleton
• cytoskeleton
• Microtubules: at 22 nm, the largest of the
cytoskeletal structures; composed of tubulin
• Microfilaments: at 6 nm, the smallest visible
with standard EM; composed of actin (G-
form), which forms twisted strands (F-form).
• Intermediate filaments: stable protein
strands, 7-10 nm; Provide a stable framework
within the cell.
Functions.
• Formation of the shape of the cell.
• Involved in the process of contraction and
relaxation of the muscle.
• Involved in the process of cell division
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Cytoskeleton for support and
transport

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Remember ….
Cytoskeleton
•Shape
•Strength
•Support
•Transport
•Cell to cell links

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Cell physiology cont… • Centrosome
- Part of cell division (see Histology… !!!)
• Located near the nucleolus in the cytoplasm.
• The centrosome made up of 2 centrioles and surrounding material.
• Centriole made up of microtubules in groups of 3 run longitudinally
in the walls of each centriole.
• There are 9 of these triplets spaced at regular intervals around the
circumference.
• Centrosome absent in the nerve cells and nephrones.

• Function:
• Centrosome involved in the process of cell division.
• It direct DNA movement during cell division .

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Cell physiology cont. Definition:
Cell junction is the connection between the neighboring cells.
Cell junctions
Or it is the contact between the cell and extracellular matrix.

It is also called membrane junction.

Classification of cell junctions:

There are three types of cell junctions:
1. Occluding junctions (tight junction:-prevents the movement of ions
and large molecules from one cell to another cell.)
2. Communicating junctions (gap junctions:- propagation of
intracellular ions from one cell to the neighbor cell)
3. Anchoring junctions (filamentous junction:- are mechanical
attachments of the cells)

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Cell junction: Tight Junction
• It is the intercellular occluding junction
which available in the
• endothelial and epithelial tissues
• It forms from fusion of integral proteins in
the apical parts of the cells
• It is made up of a ridge which has two halves
and both halves of the ridge fuse with each
other very tightly and occupy the space
between the two cells
• Consists of tight junction membrane
proteins which strength cells
• It prevents the passage of large molecules

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Stucture-proteins of tight junction
1. Tight junction membrane proteins or
integral membrane proteins, such as
occludin, claudin and junctional
adhesion molecules (JAMs)
2. Scaffold proteins (fencing function)
which builds a cytoplasmic plaque
proteins such as occluding, cingulin, symplekin and
ZO1, 2, 3. The scaffold (platform) proteins are
attached with the tight junction membrane proteins
and strengthen the anchoring in the ridges

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Function of tight junction
• Strength and stability of the tissue.
• Selective permeability (gate
function) for small molecules but not
for ions.
• Fencing function: for that we say
that it is impermeable CM junction.
• Blood-brain barrier (BBB) between
blood vessels, astrocytes and
neuron.

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Abnormalities of tight junction
• Disorders in the BBB leads to a lot of brain disorders –
harmful substances passing feely to the neurons
• Inflammatory bowl diseases (IBD) like ulcerative bowl
colitis, inflammation in the GIT leaky Gut syndrome etc
• Colon cancer and cancer metastasis
• Celiac disease due to ingestion of glutin
• Hereditary deafness,
• Ichthyosis (scaly skin)
• Sclerosing cholangitis (inflammation of bile duct causing
obstruction)
• Hereditary hypomagnesemia (low level of magnesium in
the blood)
• Synovial sarcoma (soft tissue cancer)
• Functions of tight junction are affected by some bacteria
and viruses also.

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 Communication junction: Gap Junction
✓ It forms between the cells as a chemical synapse.
✓ Chemical synapse is the junction between a nerve fiber and
a muscle fiber (Neuromuscular junction) or between two
nerve fibers, through which the signals are transmitted by
the release of chemical transmitter
✓ It permit the intercellular exchange of ions and substances.
✓ It is presented in heart, basal part of epithelial cells of
intestinal mucosa.
✓ It consist of gaps (channels) where the cytoplasm of the two
cells is connected by the channels formed by the
membranes of both cells.
✓ So, the molecules move from one cell to another cell
directly through these channels, without having contact
with extracellular fluid (ECF).
✓ The channel or gap junction is surrounded by 6 subunits of
proteins which are called connexins or connexons

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Function of Gap junction
1. The channel permits the passage of
glucose, amino acids, ions (electrical
signals) and other substances, which
have a molecular weight less than
1,000
2. It helps in the exchange of chemical
messengers between the cells
3. It helps in rapid propagation of
action potential in the heart
muscles from one cell to another
cell.
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Abnormalities of Gap Junction
• The channels is made of protiens, so any mutation in
the gene-protein will cause a lot of abnormalities.
• Cardiovascular diseases like arrhythmia
• Deafness (hearing loss)
• Keratoderma (thickening of skin on palms and soles)
• Cataract (opacity of lens in eye)
• Peripheral neuropathy (damage to the nerves of
peripheral nervous system)
• Charcot-Marie-Tooth disease (a form of neuropathy)
• Heterotaxia (abnormal arrangement of organs or
parts of the body in relation to left right symmetry).

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 ‫ تلعب دوًرا حاسًما في‬:(Actin Filaments) ‫العضلية النشطة‬
‫يتلعمبليادوتًرا حاسًما في‬:‫(ف‬Actin
‫ تشارك‬Filaments
.‫شمطاةله)يكلي للخلية‬ ‫ضفلي ةر الندع‬ ‫الحركة الخلوياةلعوتو‬
‫ك في عمليات‬.‫شياةر‬‫التح‬.‫سلايةم‬
‫جخ‬‫يموتالحهريكل ايأل لل‬
‫مثل التقسيم الخاللوحيركوةتغايليخرلواليةشوكتلوفايلرخاللودع‬
Anchoring junction .‫مثل التقسيم الخلوي وتغيير الشكل الخلوي وتحرك األجسام الحية‬

• It presents in the connective epithelial tissues

• It is acting like mechanical attachment between the
cells and extracellular matrix.
• It present in the tissues like heart muscle and
epidermis of skin, which are subjected to severe
mechanical stress.
• It is classified into four types:
• Actin filament attachment Intermediate) ‫ األلياف الوسطية‬-
• Adherens junction (cell to cell) ‫ تعمل على تعزيز متانة ومقاومة‬:(Filaments
• Focal adhesion (cell to matrix) ‫ تشكل هياكل‬.‫الخلية للتوتر والشد امليكانيكي‬
• Intermediate filament attachment ‫شبكية متقاطعة داخل الخلية وتساعد في تثبيت‬
‫ كما تلعب دوًرا هاًما في‬.‫وتحميص الخاليا‬
• Desmosome (cell to cell) ‫الحفاظ على تكامل املجموعات الخلوية وتوزيع‬
• Hemidesmosome (cell to matrix .‫القوى امليكانيكية‬

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 Function of anchoring junction
• Adherens junction provides strong mechanical
attachments (structural integrity) of the adjacent cells.
• Adherens junction is present in the intercalated disks
between the branches of cardiac muscles.
• The adherens junction present in epidermis helps the skin
to withstand the mechanical stress.
• Cell to cell junction like tight and desmosomes (macula
adherens) are function to strength the tissues.
• Desmosomes function like tight junctions.
• The transmembrane proteins involved in desmosome are
mainly cadherins.
• Hemidesmosomes are attaching cells to the extracellular
matrix.
• Mostly, the hemidesmosome connects the cells with their
basal lamina. The proteins involved in this are integrins. It
helps to transmission of the force to hall tissue
• Hemidesmosomes – need for epithelial regeneration
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‫وظيفة أنظمة االتصال الثابتة )‪ (Anchoring Junction‬تكمن في توفير ربط ميكانيكي قوي بني الخاليا املجاورة وبني املصفوفة الخارجية‪ ،‬مما يؤدي إلى تعزيز االستقرار الهيكلي لألنسجة‪ .‬إليك‬
‫شرح لبعض الوظائف الرئيسية ألنظمة االتصال الثابتة‪:‬‬

‫‪ .1‬االلتصاق البؤري )‪:(Adherens Junction‬‬

‫‪ -‬يوفر رب ً‬
‫طا ميكانيكًيا قوًيا بني الخاليا املجاورة‪ ،‬مما يسهم في تعزيز التماسك الهيكلي لألنسجة‪.‬‬
‫‪ -‬يتواجد في األقراص البينية بني فروع العضالت القلبية‪ ،‬حيث يلعب دوًرا هاًما في التنسيق االنقباضي للعضالت القلبية‪.‬‬

‫‪ .2‬االلتصاق البؤري في الطبقة الباطنية )‪:(Adherens Junction in Epidermis‬‬

‫‪ -‬يساعد في تعزيز مرونة الجلد ومقاومته للتوتر امليكانيكي‪.‬‬
‫‪ -‬يلعب دوًرا هاًما في تحمل الجلد للقوى الشد والتمدد‪.‬‬

‫‪ .3‬االتصال خلية بخلية )‪ (Cell-to-Cell Junction‬مثل االتصال الشديد والدسموسوم )‪:(Macula Adherens‬‬
‫‪ -‬يعزز قوة األنسجة ويحسن التصاق الخاليا‪.‬‬
‫‪ -‬وظيفة الدسموسوم تشبه وظيفة االتصال الشديد‪.‬‬

‫‪ .4‬الدسموسوم‪:‬‬
‫‪ -‬يعتمد على الكادهيرينات )‪ (Cadherins‬كبروتينات غشائية رئيسية‪.‬‬
‫‪ -‬يساهم في تعزيز التصاق الخاليا وتوفير الدعم الهيكلي‪.‬‬

‫‪ .5‬الهميدسموم‪:‬‬
‫‪ -‬يربط الخاليا باملصفوفة الخارجية )الباملينا(‪.‬‬
‫‪ -‬يستخدم االنتجرينز )‪ (Integrins‬كبروتينات غشائية رئيسية‪.‬‬
‫‪ -‬يساعد في نقل القوى امليكانيكية إلى األنسجة بأكملها‪.‬‬

‫‪ .6‬الهميدسموم ‪ -‬الحاجة إلى تجدد الطبقة الباطنية )‪:(Epithelial Regeneration‬‬

‫‪ -‬يلعب دوًرا هاًما في عملية تجديد الطبقة الباطنية لألنسجة‪.‬‬

‫بشكل عام‪ ،‬يتم توظيف أنظمة االتصال الثابتة في تحسني التماسك الهيكلي لألنسجة وتعزيز القوة امليكانيكية للخاليا واألنسجة في الجسم‪.‬‬
Abnormalities in the anchoring junctins
• Dysfunction of adherens junction and focal
junction in colon due to mutation of proteins
results in colon cancer.
• It also leads to tumor metastasis (spread of
cancer cells from a primary tumor to other parts
of the body)
• Dysfunction of desmosome causes bullous
pemphigus (autoimmune diseases characterized
by production of autoantibodies against
desmosomes proteins. It leads to develop
painful sensation and erosion of skin mucous
membrane.
• Cardiomyopathy
• Skin cancer

AKA Cell and Transport 47

Summary of cell junctions

AKA Cell and Transport 48

Cell physiology cont… Nucleus
• Control center of the cell.
• Contains genetic information
– DNA and nucleolus (Site of
ribosome's synthesis).
• Covers by two layers of bilayer
lipid membrane called nuclear
envelop.

Functions of the nucleus

• Controls cell activity (Secretory
and synthesis functions).
• Controls cell division and hereditary.
• Site of formation of RNA (nucleus)
and ribosomes (nucleolus).

AKA Cell and Transport 49

Summary of cell
physiology
Cell

Cell Membrane Cytoplasm Nucleus

Structure Contents of cytoplasm

Functions Function of each organelle

1. Protection
2. Separation • Mitochondria
3. Transport • ER: SER and RER
4. Recognition • Golgi app. • Control –DNA
• Lysosomes • Nucleolus
5. Junctions
• Nuclear
6. Communication • Peoxisomes membrane
Receptors • Centrosomes
Carriers • Cytoskeleton
Channels

AKA Cell and Transport 50

Thank you

AKA Cell and Transport 51

Transport across the cell
membrane
Prof Dr Ahmed Kaid Allow
2023
AKA Transport across the cell membrane 53
ILOs
• By the end of this topic students
should be able to understand
• the purpose of transport across
the cell membrane and its clinical
implications
• the different between active and
passive transports
• Osmosis
• Endocytosis
• Exocytosis

AKA Transport across the cell membrane 54

Why we need study the transport across the cell membrane ?

AKA Transport across the cell membrane 55

Transport – introduction

• It is the movement of fluids and

electrolytes across the cell
membrane.
• Passive
• Active

AKA Transport across the cell membrane 56

Differences between active and passive transport across the cell
membrane

AKA Transport across the cell membrane 57

 Passive transport
• Passive transport - The movement of a
chemical substance across a cell
membrane from high to low concentration,
chemical and electrical gradients and
without expenditure of energy
• So in conclusion:
• It is a movement of substances from high to low its
gradient.
• No need for energy It is a movement of wanted substances (like O2; Glucose AA,
• Carriers is needed – (ex facilitated diffusion) FFA) and excretion of unwanted –CO2 (waste products of
metabolism) according its gradients so it is not need to
• It depends on the size of substance; lipid solibility of
utelise ENERGY.
Substances and saturation of carriers.
Disorders of this kind of transport lead to diseases
(impairment in the normal function)…ex
• It divided into simple or facilitated Low O2--- Hypoxia
diffusions High CO2 ---Hypercapnia ; Low Glucose---Hypoglycemia etc
AKA Transport across the cell membrane 58
 Passive transport
simple Diffusion

• Diffusion of substances from high to low its

gradients
• No needs for carriers
• No need energy
• Continuous process until T-max or V-max

• Physiological Role (benefits):

• Movement of wanted (like nutrition –
Glucose AA FA FFA etc ) from outside to
inside the cells.

AKA Transport across the cell membrane 59

Passive transport
Facilitated diffusion
• Facilitated diffusion is also called carrier-mediated
diffusion or transport
• The carrier facilitates diffusion of the substance to the
other side but with a acrrier.
• In facilitated diffusion the rate of diffusion approaches a
maximum, called V-max, or T-Max
• Carriers are needed
• No energy used
• Transport increases according to the gradient of
transported substance.

Absorption and reabsorption of wanted substances like glucose;

AA, Clacium, Na+ ,…etc

AKA Transport across the cell membrane 60

 Active transport
Primary Active Transport and
Secondary Active Transport

• Active transport is divided into two

types according to the source of the
energy used to cause the transport:
• primary active transport (uses fresh energy is
derived directly from breakdown of adenosine
triphosphate (ATP)and
• secondary active transport. uses stored
energy.

Stop of Na+-K+ pump lead to stop Sodium-Potassium Pump

(Pump of the Life)
the function of the cell – tissue –
organ-system-and finally stops life.
AKA Transport across the cell membrane 61
Sodium-Potassium Pump
Pump of the Life
• Na+-K+ Pump or Na+-K+ ATP-ase Pump
• Pumping 3 Na+ to outside and 2K+ to
inside the cell.
• 1. It has three receptor sites for binding
sodium ions on the portion of the protein
that protrudes to the inside of the cell.
• 2. It has two receptor sites for potassium
ions on the outside.
• 3. The inside portion of this protein near
the sodium binding sites has ATPase
activity.
If this pump will stop so the function of
the cell Or tissue will be stopped, too -)
AKA Transport across the cell membrane 62
Abnormities of Na+-K+ pump
• Abnormalities in the number or
function of Na+-K+ pump are
associated with several
pathological conditions.
Important examples are:
AKA Transport across the cell membrane
• 1. Reduction in either the
number or concentration of
Na+-K+ pump in myocardium is
associated with cardiac failure
• 2. Excess reabsorption of sodium
in renal tubules is associated
with hypertension.
• 3. abnormalities in this pump in
CNS leads to anxiety and
dementia
63
Co-transport transport is a secondary active transport
• Co-transport (Symport)- means two
substances coupled into one protein-carrier
and transports into the opposite direction.
• Glucose and many amino acids are
transported into most cells against large
concentration gradient.

• Sodium co-transport of glucose and amino

acids occurs especially through the epithelial
cells of the intestinal tract and the renal
tubules of the kidneys to promote absorption
of these substances into the blood.

AKA Transport across the cell membrane 64

Counter transport – also an active transport
• Is a coupling of 2 substances to
one carrier and moving against
its gradients into the opposite
direction.

e.g.: reabsorption of one Na+-ion in

the renal tubules one H+ion will be
excreted into the renal lumen.
If the Na+ can not be reabsorbed
and H+ can not be excreted so the
condition will called ACIDOSIS.

AKA Transport across the cell membrane 65

Osmosis

• Osmosis is the randomly movement of the

water in to the side of NaCl

• It controls by osmotic pressure

• Osmotic pressure prevents osmosis

1. Maintenance of normal cellular metabolism and

normal extra- and intracellular fluids.
2. Disorders will lead to diseases like edema and
dehydration

AKA Transport across the cell membrane 66

Osmolarity and Osmolality
Osmolarity
• It describe the number of osmoles of solutes in the
1 lter of body fluids (Osmol/L).
• It assist the tonicity of solution
• Molecules which involved in the determination of
osmolarity is NaCl, CHO, Proteins and Urea.
• Osmotic pressure in solutions depends upon
osmolality. However, in practice, the osmolarity
and not osmolality is considered to determine the
osmotic pressure because of the following
reasons:
• Measurement of weight (kilogram) of water in solution
is a difficult process
• Difference between osmolality and osmolarity is very
much negligible and it is less than 1%.
AKA Cell and Transport
Osmolality
• It describe the concentration of solutes in the 1 Kg
of body tissue (Osmol/1kg H2O).
• It assist the tonicity of solutes in one Kg of body
mass
• Molecules which involved in the determination of
osmolarity is NaCl, CHO, Proteins and Urea
• Osmotic preassure mades by the number of
osmoles in the one Kg of body tissue.
• Change in osmolality of ECF affects the volume of
both ECF and ICF.
• When osmolality of ECF increases, water moves
from ICF to ECF. When the osmolality decreases in
ECF, water moves from ECF to ICF. Water
movement continues until the osmolality of these
two fluid compartments becomes equal.
67
Tonicity
Tonicity
• It refers to the effect of a solution on
the osmotic pressure and water
movement across the semipermeable
membrane.
• It is a measure of the relative
concentration of solutes in a solution
compared to the concentration of
solutes inside the cells or tissues.
AKA Cell and Transport
Categories of tonicity
• Hypertonic solution: contains high
concentration of solutes compare to
the concentration of solutes on the
other side of membrane...like Mintol
or
• Hypotonic solution – lower
concentration of solutes compare to
the concentration of solutes on the
other side of membrane.
• Normotonic solution or isotonic
solution like 5% Dextrose or 0.9%
Nacl
68
Pressures of the body fluids
• Osmotic pressure .... Physiologic role and Abnormality
• Oncotic pressure ... Physiologic role in relation to the protein
concentration and its abnormalities
• Plasma colloid osmotic pressure - Physiologic role and Abnormality
• Hydrostatic pressure - Physiologic role and Abnormality
• Osmotic pressure of the plasma or tissue
• Hydrostatic pressure of plasma and tissue
• Dehydration – causes and symptomes see body fluids
• Overhydration – causes and symptomes see body fluids

AKA Cell and Transport 69

 Steps of endocytosis are:
1. Attachment to the outer layer of the cell membrane
Endocytosis 2. Invagination
3. Engulfment to inside the cells
• It is a type of transport across
the cell membrane.
• It is divided into:
• Phagocytosis (cell eating) and
• Pinocytosis (cell drinking)
• During endocytosis a bulk of
material solid or liquid is captured
by the cell membrane.

So it is required for engulfment of large proteins or

Bacteria, microbes or dead tissues for lysis like leukocytes.

AKA Transport across the cell membrane 70

 Steps of endocytosis are:
1. Attachment of secretory vesicle into the inner layer
Exocytosis of the cell membrane
2. Ward of the cell membrane
• It is a type of transport across 3. Rapture of the cell membrane and excretion of the
cell
the cell membrane.
• During exocytosis a secretory
vesicle like protein will excrete
to outside the cell.

So it is required for transport of large proteins,

hormones e.t.c to outside the cell.

AKA Transport across the cell membrane 71

Gated channels are divided into three
categories
Gated Channels Gated channels
are divided into three categories:
1. Voltage-gated channels
2. Ligand-gated channels
3. Mechanically gated channels.
AKA Transport across the cell membrane
• Mechanically gated channels
are the channels which are
opened by some mechanical
factors. Examples are, channels
present in the pressure
receptors (Pacinian corpuscles)
and the receptor cells.
72
Different types of channels
Voltage gated channels
• Open when there is a changes in the
electrical potential . Like influx of
calcium in the nerve terminal when
the signals reach it.
AKA Transport across the cell membrane
Ligand-gated channels
• Ligand = hormone and channels
specialized for hormone is the ligand-
gated channels.
• So, ligand-gated channels are the type
of channels which open in the
presence of some hormonal
substances.
• Like Ach action in the postsynaptic
membrane where it cause influx of
sodium ions into the cells so these
channels are ligand-gated channels.
73
Gated channels are divided into three
categories
Gated Channels Gated channels
are divided into three categories:
1. Voltage-gated channels
2. Ligand-gated channels
3. Mechanically gated channels.
AKA Transport across the cell membrane
• Mechanically gated channels
are the channels which are
opened by some mechanical
factors. Examples are, channels
present in the pressure
receptors (Pacinian corpuscles)
and the receptor cells.
74
Different types of channels
Voltage gated channels
• Open when there is a changes in the
electrical potential . Like influx of
calcium in the nerve terminal when
the signals reach it.
AKA Transport across the cell membrane
Ligand-gated channels
• Ligand = hormone and channels
specialized for hormone is the ligand-
gated channels.
• So, ligand-gated channels are the type
of channels which open in the
presence of some hormonal
substances.
• Like Ach action in the postsynaptic
membrane where it cause influx of
sodium ions into the cells so these
channels are ligand-gated channels.
75
Pressures in the human body
Osmotic pressure Hydrostatic pressure Colloid pressure

• Made presence • Made presence

• A pressure made of fluids in the of proteins in the
by the presence of environment environment
solutes in the
fluids. • Like fluids in the • Like plasma
blood creates colloid pressure
• Increase osmotic
pressure prevents plasma in the blood
osmosis. hydrostatic creates plasma
pressure . hydrostatic
pressure .
AKA Transport across the cell membrane 76
Abnormalities in the sodium channels
• Dysfunction of sodium channels leads
to muscle spasm and Liddle’s
syndrome (dysfunction of sodium
channels in kidney resulting in
increased osmotic pressure in the
blood and hypertension).
AKA Transport across the cell membrane
• Potassium Channel Diseases
Potassium channel dysfunction causes
disorders of heart, inherited deafness
and epileptic seizures in newborn.
• 3. Chloride Channel Diseases
Dysfunction of chloride channels
results in formation of renal stones
and cystic fibrosis. Cystic fibrosis is a
generalized disorder affecting the
functions of many organs such as
lungs (due to excessive mucus),
exocrine glands like pancreas, biliary
system and immune system
77
Thank you

AKA Transport across the cell membrane 78

Thank you

AKA Transport across the cell membrane 78

Thank you

AKA Transport across the cell membrane 78

 Blood Physiology

Prof. Dr Ahmed Kaid Allow

Reproductive Physiologist
Director of Alaw Fertility Center (since 1998)
Sana’a Yemen

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 1

 ILOs 1

• By the end of this part “blood physiology” students should be able,

physiologically, to discuss the following:
• Structure of the blood: plasma and blood cells.
• Plasma Proteins: function; A/G ratio; lipid profile
• Red blood cells; erythropoiesis; Regulation of erythropoiesis.
• White blood cells; types; functions; clinical implications.
• Immunity: Innate immunity; Acquired immunity;
• Components and steps of immune response.
• Cytokines; types and clinical implications.
• Memory blood cells. Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 2
 Remember the following as we has
discussed before in details
• Total body fluid; types of body fluids (ICF and ECF)
• Osmolarity and osmolality; hyperosmolarity and hypoosmolality.
• Osmotic pressure; oncotic pressure; plasma colloid pressure;
hydrostatic pressure.
• Active and passive transport and its abnormalities
• Hypotonic, normotonic, and hypertonic solutions.
• Plasma osmolarity is normally equal to extracellular abnormalities

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 3

Blood Physiology - 2

Introduction
• Generally, blood is a part
of circulatory system
(ECF)
• It consists of fluid (blood-
plasma) and blood cells.
• Its volume is about 8% of
the total body weight (5 L in
a 70-kg adult man).
• About 55% of this volume
is plasma which is a fluid
and the 45% is the volume
ofAhmed
Introduction: Blood Physiology, Prof Dr. blood cells.
Kaid Allow 4
 3

Body Fluid Compartments.

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 5

 3

Blood Composition

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 6

 4
Difference between plasma and
serum.
• Plasma contains
fibrinogen proteins.

• Following centrifugation
of whole blood or plasma
serum (Plasma
without fibrinogen)

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 7

 5
Blood volumes of various elements of
the circulation in a person at rest.

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 8

 6
Blood physiology –
Introduction cont.

• Different types of

W. B. Cs.

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 9

 7
Hematopoiesis in fetus and
adult human beings
• In the fetus – blood cells are
formed in the liver and spleen.

• In adult - are formed in the bone

marrow (axial skeleton).

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 10

 8

Functions of the blood

• Blood performs two major functions:

• Transport function of
• oxygen and carbon dioxide
• food molecules (glucose, lipids, amino
acids)
• ions (e.g., Na+, Ca2+, HCO3−)
• wastes (e.g., urea)
• hormones
• heat
• Defense function – WBCs.

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 11

 9

Plasma of the blood

Composition of blood
plasma
Percent
Component
(%)

Water ~92
Plasma Proteins 6–8
Salts 0.8
Lipids 0.6
Glucose (blood sugar) 0.1

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 12

 10

Plasma Proteins
• The plasma proteins consist of albumin,
globulin, and fibrinogen fractions.
• Normal plasma proteins concentration = 6.0-8.0
g/100 mL
• Plasma protein :
albumin (4.0-5.0 g/100 mL),
globulins (2.0-3.0 g/100 mL)
and fibrinogen (0.3 g/100 mL).

• Hyperprotienemia

• Hypoprotienemia

• Afibrinogenemia

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 13

 11

Albumin globulin ratio

• Albumin (Synthesized in the liver)
• Globulin (Synthesized in the
reticuloendothelial system).
• Normally, it is 1.5 to 2.5
• A/G ratio is markedly low in liver disease
because albumin levels are lower, and
globulin levels higher than normal.

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 14

 12

Functions of plasma proteins

• 1). Osmotic pressure
• 2). Viscosity
• 3). Buffering action
• 4). Protein reserve
• 5). Antibodies
• 6). Coagulation and anticoagulation
• 7). Transport function
• 8). Nutritional function

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 15

 13

‫بداع‬%‫التفكير الصامت مفتاح ا‬

!!!!!

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 16

 14
Hemopoiesis: stages in the
development of blood cells.

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 17

 15

Erythrocytes – Red Blood Cells

• Biconcave shape-cells
without nucleus and without
mitochondria.
• Glucose transported by
carrier mediated transport.
• a mean diameter of about 7.8
micrometers and a thickness
of 2.5 micrometers

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 18

 16

Erythrocytes – Red Blood Cells

• It formed in the BM and
destroyed in the spleen.
•1% of RBCs destroyed per
day.
• This amounts to 250 billion
cells per day.
• The same amount also
formed / day.
• Life span 120 days.

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 19

 17

Regulation of erythropoiesis
•Erythropoietin by the
kidneys… in patients with
chronic renal failure there
is an anemia.
•Androgens - It stimulates &
potentiates the action of
erythropoietin.
•Estrogens - suppresses the
erythropoietin secretion.
•Why the RBCs
man>women?
Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 20
 18

Regulation of erythropoiesis
• Thyroxin, cortisol and
growth hormones – via in
the requirement of tissues
to O2 So it causes
stimulation of erythropoiesis.
• E2 – suppresses it
• Tissue hypoxia ..!!!
Stimulate it.
• Hypothalamus-sense to
hypoxia-→↑ erythropoietin
• Products of Hemolysis →↑
erythropoietin
Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 21
• Dietary Factors-AA, iron,
 19
Erythrocyte parameters:
MCH, MCV, and MCHC

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 22

 20

Hemoglobin (Hb)
• Hb is a protein oxygen-carrying pigment
in the RBC.
• It consists of 4 polypeptide
chains(Globin molecule) + Heme.
• In normal Hb-A there are two types of
polypeptide chains ( 2α = 141AA and 2-
Beta = 146 AA).

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 23

 21

Myoglobin
• Single polypeptide

• 16,700 daltons

• 8 a helices (A-H)
• Located in skeletal & cardiac muscle

• [high] in diving mammals like whale &

seals

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 24

 22

CO Poisoning

• Carbon monoxide is a dangerous gas since it

causes death.
• This gas was used by Greeks and Romans for the
execution of criminals.
• Carbon monoxide causes more deaths than any
other gases.
• CO is “competitive inhibitor” of O2. Affinity of
CO is 200X greater than that of O2.
• Common sources for carbon monoxide are exhaust
of gasoline engines, coal mines, gases from guns,
Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 25
deep wells and underground drainage system.
 23

Iron
Metabolis
m
in the
Human
Beings.

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 26

 Hemoglobin 24

Heme Globin

Catabolism of Amino Acids

hemoglobin in MPS

Bilirubin

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 27

 25
Pathophysiology of RBCs-
Hb abnormality
1. Methemoglobin/Hb-M. Normal methemoglobin level is 0.6% to 2.5% of total
hemoglobin. It is the abnormal hemoglobin present in the form of methemoglobin. It
occurs due to mutation of genes of both in α and β chains, resulting in abnormal
replacement of amino acids. It is present in babies affected by hemoglobin M disease or
blue baby syndrome. It is an inherited disease, characterized by methemoglobinemia. It
is counteracted by erythrocyte protective system called nicotinamide adenine dinucleotide
(NADH-methemoglobin redoctase system) system which converts methemoglobin back
to hemoglobin.
2. Carboxy-Hb- (normally is 3% to 5 % ) it has low affinity to bind with O2.
Carboxyhemoglobin or carbon monoxyhemoglobin is the abnormal hemoglobin derivative formed by the combination
of carbon monoxide with hemoglobin. Carbon monoxide is a colorless and odorless gas. Since hemoglobin has 200
times more affinity for carbon monoxide than oxygen, it hinders the transport of oxygen resulting in tissue hypoxia
(Chapter 127). Normally, 1% to 3% of hemoglobin is in the form of carboxyhemoglobin.

3. Hemoglobinopathies, e.g. thalassemias (Decrease or absence in the α and β

polypeptide chains. e.g. Hb-S, the α-normal but β-abnormal, glutamic acid //
valine=sickle-shaped erythrocytes. Hemoglobin in Thalassemia and Related Disorders In
thalassemia, different types of abnormal hemoglobins are present. The polypeptide chains
are decreased, absent or abnormal. In α-thalassemia, the α-chains are decreased, absent or
abnormal and in β-thalassemia, the β-chains are decreased, absent or abnormal

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 28

 Example of Hb mutation: Sickle cell 26
HbA anemia
HbS
Normal Hb

HbA - composed of 4 polypeptide chains 2 - and 2 -

chains
In the -chain of globin, the glutamic amino acid is replaced by
valine amino acid at the position number 6 in one polypeptide
chain of Hb, due to mutation in the structural gene.
6
The -chain
of Hb

The -contains 141 amino acids and

-chain contains 146 amino acids.

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 29

 27
Laboratory differences between folic acid
and B12 anemias.

Anemias Clinical and

laboratory tests
Folate deficiency
anemia
B12 deficiency anemia

Origin Usually dietary Rare dietary

Patients with mal-
• Reduction in Hb or in the It is common in Pregnant women
absorption of B12
number of RBCs Due to Hb
1. Production of RBC. Due Macrocytic, Macrocytic,
Hematological
to bone-marrow suppression features
megaloblastic , megaloblastic ,
or low intake of components normochromic anemia normochromic anemia

of Hb or RBCs. Erythropoietin
1. Iron deficiency anemia: production
Normally, it is present in ferrous Large and immature Large and immature
(Fe2+) form. RBC
(megaloblasts) (megaloblasts)
2. Folic acid and
uniform in size
3. Vitamin B12 Deficiency anemias Form and
(Anisocytosis) nor in Anisocytosis and
appearance of
appearance poikilocytosis are seen
2. Hemolysis-early breakdown RBC
(Poikilocytosis)
of RBCs. It called hemolytic Symptoms of
anemia. It appeared due to anemia
Presented Presented
abnormalities in the shape of Neurological
RBCs. disorders
Not involved Involved

3. Hemorrhage: bleeding due Serum levels of

Folic acid only B12 and folate are
folate and B12
to trauma or during surgery or
Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 30
bleeding during pregnancy or Orally tablets of folic Orally folic acid
supplementation +
after labor. Therapy acid and green leafy
 28

Jaundice
• Jaundice is yellowish discoloration of the skin and eyes
due to an elevation in the concentration of bilirubin in blood
≥ 2.5 mg/dL (Normal range of bilirubin in the serum up to
1 mg/dl).
1. Physiological Jaundice-appears in infants in the
neonatal period (1-28 days after birth). It is due to
change Hb-F to Hb-A.
2. Pathophysiological Jaundice – due hemolytic anemia
or hepatitis or post hepatic bile obstruction.
• 1) Increase in the production of bilirubin (Hemolytic jaundice).
• 2). Decrease in the excretion of bilirubin. Hepatitis or obstruction .

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 31

 29

2) Leukocytes (WBCs)
• Leukocytes, only blood components that are complete cells:
• Make up only 1% of the total blood volume
• Can leave capillaries via diapedesis and
• move through tissue spaces
• Normal WBCs in the blood 4,000-11,000/mm3
• Leukocytosis – WBC count over 11,000 / mm3
• Normal response to bacterial or viral invasion
• Two main types named for whether “granules” are visible under
microscope
• Granulocytes
• Agranulocytes

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 32

 30

Percentages of Leukocytes

Lymphocyt Monocyte
e

Neutrophil Eosinophil Basophi

s s l
Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow Figure 17.9 33
 31
2) Leukocytes (continued):
Granulocytes
• Granulocytes – neutrophils, eosinophils, and basophils
• Are larger and usually shorter-lived than RBCs
• Have lobed nuclei
• ALL are phagocytic cells
• Three types
A. Neutrophils
B. Eosinophils
C. Basophils

Neutrophil Eosinophil Basophi

s s l

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 34

 32
2. Leukocytes (continued):
Granulocytes: A.
Neutrophils
• Neutrophils are our body’s bacteria slayers
• Neutrophils have two types of granules
• account for 50% - 70% of WBC
• Contain peroxidases, hydrolytic enzymes, and defensins (antibiotic-like
proteins)

Neutrophilia
Neutropeina
or
Leukocytosis
Neutrophil

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 35

 33
2. Leukocytes (continued):
Granulocytes: B. Eosinophils

• Eosinophils attack parasitic worms

• account for 1–4% of WBCs
• Have red-staining, bilobed nuclei
connected via a broad band of nuclear
material
• Have red to crimson (acidophilic) large,
coarse, lysosome-like granules
• Reduce the severity of allergies by
phagocytizing immune complexes
(antigen-antibody complexes)

Eosinophi
Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 36
l
 34
2. Leukocytes (continued):
Granulocytes: C. Basophils

• Basophils are functionally similar to mast cells (detect foreign substances)

• account for 0.5% of WBCs
• Have U- or S-shaped nuclei with two or three conspicuous constrictions
• Have large, purplish-black (basophilic) granules that contain histamine,
which is an inflammatory chemical that acts as a vasodilator

Basophi
l

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 37

 35
2. Leukocytes (continued):
Agranulocytes • Agranulocytes
• Lack visible cytoplasmic granules
• Are similar structurally, but are
functionally distinct and unrelated cell
types
• Two types:
• A. Lymphocytes
• B. Monocytes:

Lymphocyt Monocyte
e

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 38

 36
2. Leukocytes (continued):
Agranulocytes: A. Lymphocytes
• Lymphocytes account for 25% or
more of WBCs
• Have large, dark-purple, circular
nuclei with a thin rim of blue
cytoplasm
• Are found mostly enmeshed in
lymphoid tissue (some circulate in
the blood)
• There are two types of lymphocytes:
• T cells (mature in thymus) function in
the immune response
• B cells (mature in bone) give rise to
plasma cells, which produce Lymphocyt
antibodies
e

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 39

 37
2. Leukocytes (continued):
Agranulocytes: B. Monocytes
• Monocytes leave the circulation, enter tissue,
and differentiate into macrophages
• account for 4–8% of leukocytes
• the largest leukocytes
• Macrophages
• Are highly mobile and actively phagocytic
• Activate lymphocytes to mount an immune
response

Monocyte

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 40

 38

Summary of formed elements

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow 41

 39

Summary of formed elements

Introduction: Blood Physiology, Prof Dr. Ahmed Kaid Allow Table 17.2.2 42
Body Temperature
Regulation
Prof Dr Ahmed Kaid Allow
Sana’a Yemen
2023
 ILOs
• What is the body temperature?
• Normal body temperature.
• Physiological variations of body temperature.
• Heat loss and heat gain
• Regulation of body temperature.
• Applied physiology– fever
• Hyperthermia
• Hypothermia.
• Physiological benefits of hyperthermia.
 What is the body temperature?
• It is refers to the body metabolic activity, or
• Refers to the measurement of the heat
production.
• It is expressed in degrees Celsius 0C or
Fahrenheit (0F)
• The body temperature is maintained by
thermoregulation which is controlled by
hypothalamus.
• Hypothalamus receives information from
temperature sensors located throughout the
body (thermoreceptors).
• An increment in the BT is a normal. It is
determined as a normal physiological
response.
 Normal body temperature
NORMAL BODY TEMPERATURE
• Normal body temperature in human is
37°C (98.6°F), when measured by
placing the clinical thermometer in
the mouth (oral temperature). It
varies between 35.8°C and 37.3°C
(96.4°F and 99.1°F).
• Core temperature is the average
temperature of structures present in
deeper part of the body. The core
temperature is always more than oral
or rectal temperature. It is about
37.8°C (100°F).
TEMPERATURE AT DIFFERENT PARTS OF
THE BODY
• Axillary temperature is 0.3°C to
0.6°C (0.5°F to 1°F) lower than the
oral temperature.
• The rectal temperature is 0.3°C to
0.6°C (0.5°F to 1°F) higher than
oral temperature.
• The superficial temperature (skin
or surface temperature) varies
between 29.5°C and 33.9°C (85.1°F
and 93°F).
 Physiological Variations of Body
Temperature
• Age:
• Infancy varies It is because the temperature
regulating system does not function
properly during infancy.
• Children 0.5 more because of activity.
• In old age, since the heat production is less,
the body temperature decreases slightly.
Unless???
 Sex:
 Low BMR – so it is less.
 Diurnal variations:
 Morning less and sleep -1 0C; afternoon
and exercise +1 0C; after meal and
Emotion +0.5 0C ;
• Heat production:
• Liver is the maximum organ for heat
production due to metabolic activity.
• Metabolic and muscular activity ▲heat
production.
• Hormones like T4 increases BMR and
Heat production.
• Shivering refers to shaking of the body
caused by rapid involuntary contraction
or twitching of the muscles as during
exposure to cold. Shivering is a
compensatory physiological mechanism
in the body, during which enormous heat
is produced.
 HEAT LOSS
HEAT LOSS

• Conduction- 30% of heat is lost

from the surface of the body to
other objects.
• Radiation-60% radiation from
body to other objects through the
surrounding air.
• Convection-15%
• Evaporation – Insensible
Perspiration-22% insensible water
loss. It is about 50 mL/hour.
REGULATION OF BODY TEMPERATURE
REGULATION OF BODY TEMPERATURE:

• Hypothalamus has two centers which

regulate the body temperature:
• 1. Heat loss center- preoptic nucleus s
of anterior hypothalamus
….Thermoreceptors; Stimulation of
preoptic nucleus results in cutaneous
vasodilatation and sweating
• 2. Heat production center, Or heat gain
center. It is situated in posterior
hypothalamic nucleus. Stimulation of
posterior hypothalamic nucleus causes
shivering.
 APPLIED PHYSIOLOGY– FEVER
Fever – Hyperthermia
• Elevation of body temperature above the set
point is called hyperthermia, fever or
pyrexia.
• It is the part of body’s response to disease.
• Beneficial effects of fever against the body
infection.
• Fever is classified into three categories:
• 1. Low-grade fever: When the body temperature
rises to 38°C to 39°C, (100.4°F to 102.2°F)
• 2. Moderate-grade fever: When the
temperature rises to 39°C to 40°C (102.2°F to
104°F)
• 3. High-grade fever: When the temperature rises
above 40°C to 42°C (104°F to 107.6°F).
• Causes infection, Hyperthyroidism, Brain lesions
Hypothermia
• Decrease in body temperature below 35°C (95°F) is
called hypothermia. It is considered as the clinical
state of subnormal body temperature.
• It is due to low metabolic activity.
• Classification of Hypothermia Hypothermia is
classified into three categories:
• 1. Mild hypothermia: When the body temperature falls
to 35°C to 33°C (95°F to 91.4°F)
• 2. Moderate hypothermia: When the body
temperature falls to 33°C to 31°C (91.4°F to 87.8°F)
• 3. Severe hypothermia: When the body temperature
falls below 31° C (87.8°F).
• Causes: Exposure to cold temperatures; Immersion
in cold water; Drug abuse ; Hypothyroidism;
Hypopituitarism, Lesion in hypothalamus
 Physiology of Growth
and Growth Factors
P ROF D R A HMED K AID N A JI A LLOW
SANAA YEMEN
2023
Inteented Learning Outcomes (ILOs)
By the end of this introduction, students should understand
◦ Meaning of growth and development of human body.
◦ Age-periods of growth.
◦ Pattern of growth and development.
◦ Factors affecting growth: Nutritional and Metabolic factors
◦ Environmental factors that affect growth of human body
◦ Hormones that interact with growth
◦ Growth, thyroid hormones and growth
◦ Vit D and PTH and growth
◦ Growth factors (definition, functions, types, characteristics, mechanisms
of action and abnormalities.
◦ Apoptosis and conclusion .
 1
Meaning of growth in the dictionary
The online Oxford English dictionary defines growth as ‘an increase in size and the amount of
something’.
In human body it is a dynamic process with somatic changes in stature, body proportion and
body composition that involves
◦ cell hyperplasia (increase in cell number),
◦ hypertrophy (increase in cell size)
◦ and apoptosis (programmed cell death).

Generally, Human growth is a complex physiological process unique to fetal life, childhood
and adolescent life that is tightly regulated by genetic, hormonal and environmental factors.
A growth factor, is a secreted biologically active molecule that can affect the growth of cells.
This definition has been expanded to include secreted molecules that promote or inhibit mitosi
s or affect cellular differentiation.

Growth-Definition
GROWTH
It is the process of physical maturation
resulting an increase in the size of the body
and various organs.
Multiplication of cells.
An increase in the intracellular substances
It is a quantitative changes of the body.
It is stopped when maturity attened
2
DEVELOPMENT
It is a functional and physiological maturation
of human individual.
It is like myelination of the nervous system and
includes
Psychological, emotional and social changes.
It is a qualitative aspects
It is continued throughout the life
It is a progressive increase in skills and ability
to perform normal functions
 3

Age periods of the growth

1. Fertilization and formation of zygote.
2. Embryonic period: first 8/40 weeks of
intrauterine life.
3. Fetus period: from 8/40 weeks till birth.
4. Infancy: from birth to 2 years.
5. Childhood From 2- 19 yrs
6. Adulthood 19-65 yrs
7. Old age – after 65 yrs
 4

Growth of
Tissue
the human
growth
body

Hyperplasia Tissue
differentiation
Hypertrophy During the
maturation embryonic life
 5

Pattern of growth and development

General- weight and height will increase until 18
years. It is controlled by
◦ gene control,
◦ hormonal,
◦ nutritional and environmental.
◦ Neural – growth of brain and spinal cord; at the end
of 5 years-brain growth=100% but the size of
neurons and dendrite branching and synapses will
continue it development
Lymphoid-organs: tonsils, thymus, spleen, lymph
nodes, and lymphoid tissues of intestine grow
until the end of second decade of human, life see
picture.
Reproductive – gonads and accessory
reproductive organs. Grows at rapid rate around
puberty.
Factors affecting growth 6

Nutritional and Metabolic factors

Balanced diet: like
◦ Proteins, fats, Carbohydrates, vitamins and minerals will play a crucial role in the process of growth
development
◦ Undernutrition and malnutrition in childhood period.
◦ Balance between anabolism and catabolism
◦ Example: Protein anabolism is favored by growth hormone and thyroid hormone and insulin.
◦ Catabolism is favored by glucocorticoids
Environmental factors 7

that affect growth of human body

PRENATAL - FETUS POSTNATAL - NEWBORN

1. Maternal malnutration 1. Nutrition.

2. Maternal infection 2. Childhood illness
3. Hormones-disorder 3. Physical environment
4. Maternal abuse. 4. Psychological environement
5. Miscellaneous. 5. Hormonal influence
Hormal factors 8

that affect growth of human body

Growth hormone:
◦ Secretion – somatotrophs.
◦ Rate of secretion- 1-2mg day and pulsatile in nature.

Clinical implications: the height of the individual during childhood is promoting

the linear growth in the skeleton.
Increase size of the muscle, connective tissue, viscera by promoting hyperplasia
and hypertrophy of cells.
Applied clinical physiology:
◦ GH is inhibited by somatostatin.
◦ GH plus IGF-1 are required for the proper growth
◦ Applied medical physiology: Dwarfism; gigantism, and acromegaly
 Hormones that interact with growth 9

Growth hormone; (Cell membrane receptors) secretes from the pituitary gland and enhances cell division and
growth and development. Abnormalities after birth dwarfism; gigantism and acromegaly.

Thyroid hormone, (Nuclear receptors) important for metabolism (basal metabolic rate) physical, sexual and
mental growth; abnormalities during intrauterine life – creationism; after berth hypo and hyperthyroidism. For
babies born with maternal hypothyroidism treatment can be done in the first 2 years of age. After 2 years it can not
cross the BBB.

Adrenal androgens, (Cytoplasmic receptors) produced by adrenal (cortex) glands DHEA (precursor for
testosterone and estrogens) and androstenedione (they are under the control of ACTH): development in the hair if
increased will lead to hirsutism in female

Sex steroids, (cytoplasmic receptors) like estrogens, progesterone and testosterone that regulate reproduction

glucocorticoids, like cortisol secreted from the suprarenal glands and regulate metabolism.

ghrelin, produced by stomach, hypothalamus, pancreas, and plays a role in regulating appetite, energy
production and stimulates release of growth hormone

leptin and

insulin – (only the lipogenesis hormone) also interact with the growth hormone-insulin-like growth factor-1 axis.
 10

Growth hormone and growth

 Growth hormone (GH) is a pituitary hormone which promots growth of human body during intrauterine
and after berth life.
 Human growth hormone (HGH), also known as somatotropin,
 it is a 191 amino acid single-chain polypeptide produced by somatotropic cells within the anterior
pituitary gland.
 As its name implies, scientists originally found it to be responsible for growth regulation during childhood.
However, research has determined that HGH is also responsible for the regulation of many of the body’s
other basal metabolic functions and operates as an acute phase stress reactant.
 It increases the growth of the body and cell division, increases the body weight and length of the body.
 GH-Receptors are in the cell membrane.
 It is working directly in the skeletal muscle, bones and adippose tissue (lipolysis).
 It is Inhanced ghrelin action.
 It is Inhanced the action of insulin.
 All these actions we will discuss it in the physiology course – Endocrine-glands-physiology.
 11

Growth Hormone - regulation

STIMULATORY INHIBITORY
 Difeciency of energy
o REM sleep
 Hypoglycemia
o Glucose
 Excersice
o Obesity
 Fasting
 Protein meal
o Cortisol
 Glucogon o FFA
 Ghrelin o Aging Gh
 Deep sleep o IGF-1
 Estrogens and androgens o somatostatin
 12

Somatomedins
 Somatomedin – A (IGF2) required during fetal life , secreted
by the liver and its secetion is largely independent of GH
 Somatomedin-B
 Somatomedin-C are not required during fetal life

 In fetus when IGF-2 is over experessed, the growth of organs

is disproportionated
 13

Applied medical physiology of GF

Hyposecretion
Dwarfism – GH deficiency
◦ IGF-1 deficiency
◦ Live-Laron dwarfism – high GH but IGF-1 and IGF-2 are low lack
functional hepatic GH

Hypersecretion of GH
◦ Gigantism
◦ Acromegaly
 Thyroid hormone and growth of nervous 14

system
 They are permissive to GH
 Req. IUL and after birth
 Nervous system – branching of dendrites , synapses
and development of mental activity and physical
activity, myelination, synapses
 Applied clinical physiology Hypothyroidism
 Cretinism
Growth and 15

androgens and estrogens

 The androgens and estrogens are responsible for
growth spurt at puberty
 Testosterone – growth in male
 Estrogen more patent than testosterone for having
action on epiphesal growth plate

 Glucocorticoids – permissive role on GH

 Insulin- lipogenesis stim growth diabetic child dont
grow
 CHO + Proteins+ Insulin= growth
 16

Vit D, PTH and growth

Vit D and PTH stimulate the intake of calcium and direct
action on the mineralization of bones.
Applied physiology:
◦ Rickets in children and osteomalasia in adult
 17

Growth factors
Often, the term growth factor is interchangeably used with the term cytokine.

Growth factors act on the cells of the growing tissues. But cytokines are concerned
with the cells of immune system and hemopoietic cells.
Growth factors has the outer cell-membrane receptors / surface cell
membrane receptors or plasma membrane-bound protein receptors.
Growth factors show tyrosine kinase activity, meaning they put a phosphate
group on a downstream protein tyrosine residue.
"Downstream" here means an event triggered after TGF-beta binding to its
receptor.

Growth factors
Growth factors (GF) are proteins which act as
◦ cell signaling molecules like cytokines
◦ and hormones. GF –stimulate cell-growth and repair,
healing, and development like epidermal growth factor
(EGF) and platelet-derived growth factor (PDGF).
Function of these factors: bind with specific surface
receptors of the target cell and activate
◦ Proliferation: rapid increase in the number of cells or
rapid reproduction of the cells
◦ Differentiation: formation of normal functioning cells in
the human body. Differentiation also reflect to the
processes that make a different tissues and organs.
◦ Maturation of these cells: development of differentiated
cells to perform its function and make a normal
homeostasis with all organs and tissues of the human
body
Cytokines: Group of small proteins which
produces by various cells like immune 18
system to modulate the immune reaction
like:
Interleukins(IL).
IL-1:- stimulate inflamation
IL-2:- promotes T-cells growth and
activation.
IL-6:- regulate inflamation and immune
responses
Tumor Necrosis Factors (TNF) playing
important roles in the process of
inflamation and cell death (apoptosis)
Interferons: antiviral agents ; inhibits
viral replications,
IFN-alpha:- and beta are important in
the defens mechanism against viral
infection.
Chemokines: coordination of immune
response.
 Growth Factor Function
Platelet-derived growth factor – PDGF Group of proteins, secreted by platelets and involve in the blood clotting, wound healings, and
repair as well as cell growth and development
Colony stimulating factors – CSF Group of proteins that regulate the production of none-marrow & immune system
Nerve growth factors – NGF Group of proteins that pay a critical role of neurons (growth, repair and development)
(synaptogenesis)
Neurotropins Group of proteins which are essintial for growth maintenance and plasticity of neurons
Erythropoietin A protein secreted by kidneys and enhances erythropoiesis in th bone-marrow
Thrombopoietin Protein that initiate the cascade blood coagulation
Insulin-like growth factors – IGFs (IGF-1 from Peptide similar to insulin. Mantain the growth over-all the body. Produced by liver, muscle,
other tissue &2 from liver during IU-life) bone, and adipose tissue. It is controlled by growth hormone. IGF-1 working after birth and
IGF-2 during intrauterine life
Epidermal growth factor present in keratinocytes and fibroblasts. It inhibits growth of hair follicles and cancer cells
Basic fibroblast growth factor present in blood vessels. It is concerned with the formation of new blood vessels
Myostatin present in skeletal muscle fibers. It controls skeletal muscle growth
Transforming growth factors (TGF) present in transforming cells (cells undergoing differentiation) and in large quantities in
tumors and cancerous tissue. TGF is of two types.
TGFα secreted in brain, keratinocytes and macrophages. It is concerned with growth of epithelial
cells and wound healing
TGFβ secreted by hepatic cells, T lymphocytes, B lymphocytes, macrophages and mast cells. When
the liver attains the maximum size in adults, it controls liver growth by inhibiting proliferation
of hepatic cells. TGFβ also causes immunosuppression.
 20

Growth factors – characterisics

Some growth factors are small peptides called cytokines.
While all cytokines affect signal transduction pathways, only those cytokines affecting
cell growth/differentiation signaling pathways are considered growth factors.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an example of a
cytokine growth factor since it promotes the production of white blood cells by stem cells.
Examples of protein growth factors are vascular endothelial growth factor (VEGF),
epidermal growth factor (EGF), and platelet-derived growth factor (PDGF).
Growth factor specificity to particular cell types is achievable by the expression of highly
specific cell surface receptors. For example, some growth factors act only on
hematopoietic cells, which are cells derived from bone marrow.
 21

Growth factors – characterisics continue

 Some growth factors like lipid-soluble steroid hormones, do not have a surface
receptor and can directly pass through the cell's plasma membrane, bind to an
intracellular protein receptor, or nuclear receptors, and then transmit a growth
signal.
 Glands produce all hormones and secrete them into the circulatory system.
 Estrogens, androgens, and progestogens are examples of steroid hormones that
are growth factors. Not all hormones are growth factors, only those affecting
cell growth/differentiation.
 Even simple small molecules such as nitric oxide or reactive oxygen species
(ROS) can act as growth factors.
 22

Apoptosis-programing cell death

 Death receptor ligands are the substances which bind with specific cell
membrane receptors and initiate the process of apoptosis. The common
death-receptor ligands are tumor necrosis factors.
 It can be programing
 and non-programing cell death.
 During the pathological disorders, it can cause non-programing cell death.
 Normal programing cell death appears during normal physiological condition
like red blood cells are dying after 100-120 days stomach mucosal cells after
6 hours to 2 days are replaced.
 Conclusion 23
Generally, Human growth is a complex physiological process unique to fetal life and childhood and
adolescent life that is tightly regulated by genetic, hormonal and environmental factors.
A growth factor, as initially defined, is a secreted biologically active molecule that can affect the growth of cells
. This definition has been expanded to include secreted molecules that promote or inhibit mitosis or affect cellul
ar differentiation.
They have a surface cell membrane receptors.
They has a kinase phosphatase activity.
All steroid hormones are working as growth factor hormones and has lipid-soluble characteristics.
Growth factors (GF) are proteins which act as cell signaling molecules like cytokines
◦ and hormones. GF –stimulate cell-growth and repair, healing, and development like epidermal growth factor (EGF) and platelet-
derived growth factor (PDGF).

Function of growth factors: bind with specific surface receptors of the target cell and activate
◦ Proliferation: rapid increase in the number of cells or rapid reproduction of the cells
◦ Differentiation: formation of normal functioning cells in the human body. Differentiation also reflect to the processes that make a
different tissues and organs.
◦ Maturation of these cells: development of differentiated cells to perform its function and make a normal homeostasis with all organs
and tissues of the human body.
◦ Many physiological activity can be deteriorate due to problems in the GH and Gf biosynthesis and action like dwarfism and
creationism.
Thank you for your attention and
Does you have any question?