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1. SECTION B PATHOLOGY MEDICAL
SCIENCE
By Dr Maepa

2. INFLAMMATION (Acute and Chronic)
1 What is inflammation?
2 What are the causes of inflammation?
3 What are the changes in inflammation?
4 What are the possible outcomes of inflammation?
https://www.youtube.com/watch?v=LArxUakFsFs
“any type of tissue damage that initiates cellular and vascular events that are
designed to clean any type of cellular debris or pathogens and initiate
repair”

3. Inflammation in general is:
• A dynamic process whereby the living tissue reacts to an injury.
• The reaction of vascularised living tissue to local injury.
What can cause tissue injury and provoke an inflammatory response?
Both internal and external factors can lead to tissue injury. Internal
factors may include hormones, genetic mutations – tumours causing
necrosis. This is not a common feature and will thus not be persued.
Only external factors will be considered.

4. The following external tissue injuries lead to
inflammation:
a. Mechanical injury – cutting and crushing
b. Chemical injury – acids, alkali
c. Physical injury – heat, light electricity, X-irradiation
d. Injury due to living organisms – bacteria, viruses, fungi and
parasites
e. Reaction to necrosis – physiologically to menstrual
endometrium, around an infarct or in the center of a tumour
f. Immunologic reaction – antigen/antibody reaction in the body
such as in autoimmune disease like contact dermatitis.

5. inflammation using bacterial infection as a stimulus:
• Acute inflammation is a rapid response to an injurious agent that serves to
deliver mediators of host defense – leukocytes and plasma proteins.
https://www.youtube.com/watch?v=LArxUakFsFs
Discussion:
Bacteria as toxin-tissue damage
Scavenger cells/Mast cells (monocytes/macrophages etc.)
Immunoglobulins (IgE+toxin+mast cells)
Histamine
Macrophages secrete cytokines and damaged tissue secrete prostaglandins
The substances evoke an inflammatory response
Phagocytosis
The complexity affects tissue and vascular environment-inflammatory changes

6. Acute inflammation
1. Injured blood vessel constriction by serotonin from platelets- to
minimize loss of blood from injured vessel.
2. Dilatation of artery supplying the injured tissue – to promote blood
flow.
3. Hyperemia – increased vascular permeability and blood flow.
4. Exudation – fluid flowing from increased permeable blood vessel to
damaged tissue (oedema). The fluid dilute toxins, transports antibodies and
drugs to the site of inflammation, contain precipitating fibrin to wall off the
area and to aid phagocytosis.
5.

7. Clinical cardinal signs of inflammation
• Redness – due to leakage of red cells.
• Heat - due to increased blood flow at 37oC.
• Swelling- due to exudation of fluid.
• Pain- due to oedema causing increased tissue tension and pressure on
nerve endings.
Release of chemical mediators of inflammation (such as bradykinin) may
cause pain.
• Loss of function- may occur following the swelling and the pain or
following inflammatory destruction of tissue.

8. CHANGES DURING INFLAMMATION-Blood Vessels
These changes involve cells within the blood vessel – cellular part of the exudate
•Slowing of blood flow.
•White cells (leucocytes) filter onto the blood vessel wall - margination.
•These cells then adhere to the vascular endothelium.
•Adhesion molecules (inflammation mediators) secreted by both the leucocytes and the
vessel endothelium facilitate adhesion.
•Leucocytes emigrate by active expansion of pseudopods through gaps in the cell junctions.
•They may then move along the vessel wall between endothelium and basement membrane until they manage to penetrate
the basement membrane and enter the tissue.
•Movement of pseudopods is carried by means of actin filaments associated with contractile protein myosin within the cell.
•Polymorphonuclear leucocytes (PMNs) arrive at the scene of inflammation in the first 6 to 24 hours and after 24 hours and
they are later replaced by the monocytes. They are capable of phagocytosis and digestion because: their cytoplasm can be
amoeboid.
•Red cells move out the vessel through a process of diapedesis.
•Neutrophil polymorphonuclear leucocyts are attracted to the scene by chemotactic agents including:
- bacterial product
- components of complement system, particularly C5a
- components of the lipoxygenase pathway of arachidonic acid metabolism especially leukotriene B4 (LTB4).

9. CLASSIFICATION OF INFLAMMATION
On what can classification of inflammation be based?
Upon the following three points:
• The nature of the inflammatory exudates
• The duration of the inflammation
• The site of the inflammation
Note: Exudate is fluid that leaks out of blood vessels into nearby
tissues. The fluid is made of cells, proteins, and solid materials. Exudate
may ooze from cuts or from areas of infection or inflammation

10. A. Classification according to the nature of
the inflammatory exudates
Exudate Example
• Serous exudation. Blisters which form after burns & pleural effusion
• in TB.
• Fibrinous exudation. Inflammation of body cavities: pleura, pericardium
• or peritoneal.
• Haemorrhagic inflammation. Influenzal pneumonia, meningococcal septicaemia
• and anthrax
• Catarrhal inflammation.Inflammation of nasopharynx, bronchi and gut.
• Pseudomembranous. Inflammation of mucosal surface- mouth,
• respiratory passages or gut.
• Suppurative inflammation. Inflammation is followed by pus production.
• Gangrenous inflammation. Following infection with putrefactive organisms.

11. B. Classification according to the duration of the
inflammation:
 Acute inflammation. This is the term used to denote the vascular and
• exudative changes. In acute inflammation, polymorphs are the
predominant cells, but with the passage of time and
neutralization of the injurious agent, macrophages accumulate
and the demolition phase starts. In this phase the macrophages
remove the dead cells and their breakdown products. The
macrophages themselves then either die or are drained
through lymphatics. Then follow healing and repair. However,
this course of events can only take place when the original
cause of inflammation has been removed. If the nonxious
• /poisonous agent persist then there may be simultaneous acute
inflammation and attempts at demolition and healing. It is at this
stage that the inflammation becomes chronic.
Note: (This is the sequence of blood cell involvement in acute inflammation to tissue
healing).

12. Chronic inflammation
Is a prolonged process in which destruction and inflammation are proceeding at
the same time as an attempts at healing. In terms of time acute inflammation
can be assumed to be entering a chronic phase after it has persisted for a week or
two. Acute inflammation may go on to become chronic for a number of reasons:
- Persistence of the injurious agent
- The presence of foreign bodies
- Delayed healing for some reason
-
The development of hypersensitivity
- Repeated bouts of acute inflammation as may occur in kidneys,
especially when there is a predisposing cause as stasis
- Lowered host resistence.

13. C. Classification of inflammation according to
site:
Inflammation may be classified according to the tissue involved, such
as:
• Appendicitis
• Tonsillitis
• Osteomylitis, generally by adding the suffix ‘-itis’ to the
anatomical name for the part affected.

14. The outcome of acute inflammation:
• Resolution (complete return to normal
• Tissue destruction and suppuration
• Healing by regeneration and repair
• Organisation of exudates- fibrosis
• Chronic inflammation
• Spread to septicaemia and even death.
The effects of chronic inflammation:
• Fever with night sweats.
• Leucocytosis with mononuclear and polymorphs.
• Increased C-reactive protein (CRP) and other proteins as produced in the liver.
• Raised erythrocyte sedimentation rate (ESR) due to high antibody content in blood.
• Loss of appetite and weight.
• Tiredness, headache and general feeling of unwellness.
• Amyloidosis is likely.

15. HEALING AND REPAIR
Inflammatiom prepares platform for healing and repair.
The major objective is to restore normal functioning of the tissue (i.e. homeostasis).
The process by which the body replaces destroyed or dead tissue by living tissue.
https://www.youtube.com/watch?v=b4AOnDLK4tQ
https://www.youtube.com/watch?v=IzQea1Ihe_M

16. HEALING
It is a fibroproliferative response that “patches” rather than restores a tissue.
This may take place in a number of ways:
• Resolution – (problem resolved) - the tissue may be completely restored
to normal, both structurally and functionally. Resolution can take place if the
original normal framework has not been destroyed (original framework having
been preserved).
• Regeneration – (extra new type of cells) - there may be proliferation of
parenchymal cells with some loss of normal architecture (architecture =
framework
= normal structure and form).
• Organisation - (organized differently)– lost tissue may be replaced with
granulation tissue and fibrous repair will take place.

17. Regeneration and organization may occur together, although if the underlying
framework has been destroyed, normal architecture may not be preserved.
Different cells of the body have different capacities for regeneration:
• Labile cells
i. These cells are constantly multiplying during life to replace cells that are being
destroyed.
ii. In this group are all cells of surface epithelia that cover the body or line
hollow organs.
iii. The cells of the bone marrow are continually making new blood cells.
• Stable cells
i. They have capacity to regenerate should the need arise.
ii. Most glandular epithelial cells and connective tissue fall into this category.
iii. Typical example is fibrous tissue with great regenerative capacity.
• Permanent cells
i. Have little or no powers of regeneration.
ii. These include nerve cells and skeletal and cardiac muscle.

18. PHASES OF HEALING/THE MECHANISM

19. EXAMPLES OF WOUND HEALING
A) Healing by first intention
This is the way in which a clean incised wound will heal if the edges are held together. Surgical
wounds heal in this fashion. The sequence of events is:
•There is bleeding into the tissue (haematoma formation).
•An acute inflammation reaction with polymorphs form around the clot with fibrin release to bind
the wound together.
•Within 24hours epithelial cells grow from the basal layer at the edge between viable tissue of the
dermis and the clot until they meet up with other epithelial cells which seem to inhibit further
growth.
•Soon the inflammation exudates begins to be broken up and resorbed by macrophages
•By about the 3rd day the wound area is filled with granulation tissue.
•Collagen fibres are laid down, at first type-III and later type-I, filling the gap.
•By the end of the 1st week the inflammatory infiltrate has disappeared and the epidermis has
regained its normal thickness.
• Blood vessels diminish in number and the scar becomes paler.
•Contraction of the scar with increasing tensile strength takes place over the next four or five
weeks.

20. B) Healing by secondary intention
It is the name given to the healing of a wound with separated edges. This is
known as healing by granulation. The pathological changes are similar but
more granulation tissue has to be formed and this process is slower and
leaves a larger scar.
• The wound is filled with a clot, which dries on the on the surface to
form a scab.
• Contraction of the skin around the edges takes place, reducing the size
of the defect.
• Epidermis grows in from the sides between clot and living cells.
• The exudates is removed by macrophages. Granulation tissue grows
into the clot replacing it and gradually becomes covered by epithelium,
leaving the scab on top which is completely undergrown and falls off.
Collagen fibres are laid down. A scar which undergoes contraction
(cicatrisation) and becomes paler is formed.

21. MECHANISMS OF REPAIR
This is the process of restoration of a healed tissue to its original state (homeostasis). A
number of growth factors will act on stable cells to bring about proliferation. These include:
• Epithelial growth factor (EGF)
• Platelet-derived growth factor (PDGF)
• Fibroblast growth factor(FGF)
• Transforming growth factor (TGFα and TGFβ)
• Interleukin -1 and Tissue necrotic factor (IL-1 & TNF)
These factors seems to be produced by most participants in the inflammatory reaction, and
may stimulate cell division, of both fibroblasts and endothelial cells and may also have a
chemotactic attraction for these cells. They can also stimulate new vessel formation.

22. FACTORS INFLUENCING WOUND HEALING:
A. General factors influencing healing
• Age. Healing is said to be faster in the
young.
• Protein deficiency
• Vitamin C (ascorbic acid) deficiency
(protein and Vitamin C are necessary for
adequate collagen strength and synthesis).
• Zink deficiency will lead to delayed
wound healing.
• Glucocortocoid steroid hormones have an
antiflammatory effect and will also delay healing
if administered in the early stages.
B. Local factors influencing healing
• Blood supply. Well vascularised tissues
heal faster; the face heals faster because the
face is highly vascularised.
• Infection of a wound, or the presence of
foreign material within it, will slow down the
healing.
• Continuous movement of the injured
part will not allow knitting together, as newly
formed granulation may be disrupted, there will
be additional heamatoma formation and the
whole process will be slowed down.
• The amount of tissue destroyed,
particularly if the supporting framework is
destroyed, is important. Big wounds take longer
to heal and show more scarring.
• X-ray therapy may impair granulation
tissue formation.

23. Complications of wound healing
• Infection may enter a wound causing additional inflammation with
tissue destruction and pus formation.
• Overgrowth of granulation tissue (‘proud flesh’) may grow through a
skin wound,
preventing epithelialisation.
• Cicatriasation or excessive contraction of a scar may cause:
- skin deformity
• Keloid formation can be troublesome. There is excess production of
mature collagen which forms a lump in the scar, stretching the overlying skin.
• Pain may result from neuroma, formed from proliferating nerve fibres
caught up in the wound.
• Weakness.
Fibrous scar tissue has reduced tensile strength and can stretch
• Cancer may sometimes develop in a chronic scarred ulcer, for
example, chronic leg ulcer.

24. PIGMENTATION
https://www.youtube.com/watch?v=roVKvIyVpwQ
Pigmentation refers to the process of developing a pigment or a colour.
Everybody is born with a colour; that will be the colour of the skin,
eyes, the hair, etc. The natural colour of an individual may intensify or
lighten or even change, due to internal or external factors –
endogenonous and exogenous factors, respectively.
Exogenous pigments are those which are introduced from outside the
body, for example by injection, implantation, inhalation or ingestion.
Endogenous pigments are produced within the body and include
melanin, lipofuscins and pigments formed from blood breakdown,
that is from the breakdown of haemoglobin from which haemosiderin,
haematin, bilirubin and the porphyrins are derived.

25. ENDOGENOUS PIGMENTS
Melanin pigment
• Brown pigment.
• Produced by melanocytes normally found in the skin, the choroids of the
eye, the hair and to a lesser extent in mucus membrane and meninges, the cortex
of the adrenals and the substantia nigra of the brain.
• It is protective against sunheat and damaging rays – without it extensive
sunburn, blistering and the development of skin cancers can occur. Albino
teenagers usually present at the hospital with squamous cell carcinoma of the face
or sun-exposed areas, due to lack of melanin in their skin.
• Melanin is formed from the metabolism of the amino acid tyrosine,
according to the following metabolic equation:
Tyrosine → tyrosinase →Dihydroxyphenylalanine → Melanin (DOPA)

26. DISORDERS OF MELANIN PIGMENTATION
Increased pigmentation
• Pregnancy – blotchy pigmentation of the face together with darkening of the nipples and
genitalia.
• Haemochromatosis – accumulation of iron within the tissues of the body. This may be
followed by excess melanin pigmentation in the skin.
• Patchy or localized melanosis may occur in freckles.
Decreased melanin pigmentation
• Albinism. In the absence of the enzyme tyrosinase, melanin cannot be formed and
sufferers have white skin, pale-blond hair and pink, non-pigmented eyes.
• Localised depigmentation can occur in vitiligo (focal loss of melanocytes within the
epidermis) or in association with other diseases such as leprosy.
Pigments related to melanin
• Ochronosis – a condition in which there is an inborn error of metabolism resulting in the
accumulation of homogentisic acid. A melanin-like pigment is deposited for example in the
cartilage of the ear, nose, larynx, trachea, joints, tendons, ligaments and fibrous tissue.
• Melanosis coli is brown or black discolouration of the mucosa of the large bowel due to
the presence of melanin-like pigment in macrophages in the lamina propria of the colon.

27. The Liver and Biliary System
https://www.khanacademy.org/science/in-in-class-11-
biology-india/x9d1157914247c627:digestion-and-
absorption/x9d1157914247c627:digestive-
glands/v/biliary-tree
Note: The biliary tract, (biliary tree or biliary system)
refers to the liver, gall bladder and bile ducts.
Bile, greenish yellow secretion that is produced in the
liver and passed to the gallbladder ... Its function is to
aid in the digestion of fats in the duodenum.
• Consists of water, electrolytes, bile acids, cholesterol,
phospholipids and conjugated bilirubin.
• Water-serves to neutralize hydrochloric acid passed
from the stomach into the small intestine
• Electrolytes (sodium, potassium, chloride, and
bicarbonate)-pH, osmolarity

28. Conjugated bilirubin (Bilirubin is a substance made when your body
breaks down old red blood cells)- liver also produces it to aid in
digestion of the food you eat
NB: Conjugation is mandatory to render bilirubin aqueous soluble
What happens when we have high levels of bilirubin???
Accumulation of bilirubin or its conjugates in body tissues produces
jaundice (ie, icterus), which is characterized by high plasma bilirubin
levels and the deposition of yellow bilirubin pigments in the skin,
sclerae, mucous membranes, and other less visible tissues.

29. Excessive Bilirubin
Signs of Abnormal Bilirubin Excretion
• Pigmented urine (bilirubinuria) and jaundice (icterus) of the sclera, oral mucous membranes,
and skin are classic signs of cholestatic liver disease. However, these findings are not specific for
hepatobiliary disease and can also be caused by hemolytic disorders.
• Acholic (gray) feces occur secondary to severe cholestasis (usually from common bile duct
obstruction), which prevents bilirubin in the bile from entering the intestinal tract and imparting the
normal brown color to the feces.

30. Disorders of Acid-Base Balance
https://www.youtube.com/watch?v=4wMEMhvrQxE
Acidosis or Alkalosis (process)
Either Metabolic or Resipratory
Acedemia (state of being)
Ph=-log[H+]
H20+CO2=H2CO3=H++HCO3-
Normal PH=7.4 (7.35-7.45)
pCO2=40 (35-45)
HCO3-=24 (22-26)

31. Compensatory Reactions
Respiratory (Lung) status
1. Respiratory acidosis (↑ pCO2)
2. Respiratory alkalosis (↓ pCO2)
Metabolic (kidney) status
1. Metabolic alkalosis (↑ HCO3-)
2. Metabolic acidosis (↓ HCO3-)

32. Buffer System
1. Lung - respiratory; associated with C02 elimination
In acidosis, the lungs hyperventilate to get rid of large amounts of C02 and in
alkalosis the lungs hypoventilate to accumulate C02 in the blood.
2. Kidney - metabolic; associated with bicarbonate excretion and
generation. Elimination of H+through phosphates and ammonia.
NB: Compensation: Metabolic acidosis is normally compensated by
respiratory alkalosis – either partially or completely. Metabolic alkalosis is
compensated by respiratory acidosis. So is respiratory acidosis and alkalosis

33. Pathologic state pH pCO2 [HCO3] [ H2CO3]
i. → → → →
ii. ↑ → ↑ →
iii. → ↑ ↑ ↑
iv. ↑ ↑ ↑↑ ↑
v. ↓ → ↓ →
vi. ↓ ↑ → ↑
vii. → ↓ ↓ ↓
viii. ↑ ↓ → ↓
↓= Low/Reduced; → = Normal; ↑ = High; ↑↑ = Higher
i. Normal situation.
ii. Metabolic alkalosis without respiratory compensation.
iii. Respiratory acidosis with full metabolic compensation or metabolic alkalosis
with full respiratory compensation.
iv. Metabolic alkalosis with partial respiratory compensation.
v. Metabolic acidosis without respiratory compensation.
vi. Respiratory acidosis without metabolic compensation.
vii. Respiratory alkalosis with full metabolic compensation or metabolic acidosis with
full respiratory compensation.
viii. Respiratory alkalosis without metabolic compensation.

34. FLUID AND ELECTOLYTE BALANCE
Mechanisms for body water maintenance
1. Drinking water
2. Loss via breathing, skin and gut
3. Kidney involvement in body water regulation
Factor that influences water regulation = Osmolality (Osmoreceptors in the hypothalamus)
↓
Antidiuretic hormone (ADH)/arginine vasopressin (AVP) secretion if Osmolality is high
↓
Increased water re-absorption by kidney tubules
Note: “Osmolality” refers to the concentration of dissolved particles of chemicals and minerals --
such as sodium and other electrolytes -- in your serum

36. Hydrostatic pressure and osmotic pressure
Hydrostatic pressure (pressure due to water) and osmotic pressure are two
pressures that control movement of water in blood vessels (intravascular) and in
the interstitial compartment.
Note: The net pressure that drives reabsorption—the movement of fluid from the
interstitial fluid back into the capillaries—is called osmotic pressure (sometimes
referred to as oncotic pressure). Whereas hydrostatic pressure forces fluid out of
the capillary, osmotic pressure draws fluid back in.
How do this pressures come about?
Oncotic pressure (especially due to albumin) and attraction of water by sodium are
two major pressures accounting for the osmotic pressure acting along the semi-
permeable blood vessel membrane of the blood vessels.
To maintain water balance between the intravascular and interstitial
compartments, the pressures acting in opposite directions on the semi-permeable
blood vessel membrane should be in equilibrium.
Any disturbance of the balance will cause water movement from one
compartment into the other.

37. SODIUM
• Maintain Healthy Fluid Balance
• Proper Muscle Contraction
• Nerve Impulse Conduction
Sodium Control Mechanisms
Glomerular filtration rate influenced by condition of decreased blood circulation
e.g. in heart problems, where sodium excretion is reduced.
Fall in renal arteriolar pressure or a drop in [sodium] in distal tubules
↓
Renin secretion(by juxtaglomerular apparatus)
↓
Angiotensin system produces aldosterone
↓
Reabsorption of sodium in the distal renal tubules

38. Intracellular Fluid (ICF) and Extracellular Fluid (ECF)
• Potassium, magnesium, phosphate and protein are major intracellular
substances
• While Sodium, chloride and bicarbonate are in higher concentration
in extracellular compartment
• Under normal circumstances:
It would be expected that sodium ions move from its region of high
concentration in the extracellular compartment into the cells.
Potassium ions would also be expected to move along concentration
gradient, i.e., out of the cells. Na/K pump on cell membrane maintains
the ions against concentration gradient. The pump is energy-
dependent.

39. Hemodynamics Disoders
https://www.slideshare.net/mariamasif99/6-
hemodynamic-disorders
Haem =blood
Dynamics = changes, whether balances or imbalances
Disorder = unfavourable, not according to protocol
Haemodynamic disorders = unfavourable and abnormal blood changes.
https://www.youtube.com/watch?v=K3tCf-EFjiQ
https://www.youtube.com/watch?v=QXIpNyxfrQA
• Hyperemia
•Congestion (passive Hyperemia)
•Oedema
•Shock

40. THROMBOEMBOLIC DISEASES
• The term ‘thrombo’ comes from the noun ‘thrombus’:-It is solid or a
semi-solid mass formed from the constituent of the blood within the
vascular system during life.
• The adjective ‘embolic’ comes from the noun embolus:-An embolus is
a detached intravascular solid, liquid or gaseous mass that is carried
by the blood to a site distant from its point of origin.
• Thrombotic disease would therefore refer to diseases characterized
by clot formation or diseases arising as the result of formed clots
• Emboli lodge in vessel leads to complete or partial vascular occlusion.
The potential consequences of such thromboembolic events is the
ischaemic necrosis of distal tissue, called infarction.

41. The development of an infarct:
•Initially there is death of cells due to the cutting of blood supply.
There is seemingly an accumulation of blood in the area from
anastomotic vessels and from venous reflux.
•The dead tissue becomes necrotic, that is recognizable structural
changes of cell death. It can truly be called an infarct. This takes from
12 to 24 hours. Usually infarcts show typical coagulative necrosis in
which the necrotic cells swell.
•Slowly reparative fibrosis takes place with the ingrowth of capillaries
and fibroblasts from the edges of the lesion. Eventually the dead tissue
is replaced and a fibrous scar is left.

42. FORMATION OF A THROMBUS
This may follow vascular injury
• In case of injury, platelets adhere to the subendothelial
microfibrils.
• Platelets secrete the contents of their α-granules.
• Platelets aggregate at the point of injury.
• Coagulation factors become activated and a fibrin clot interlaced
with platelets is formed.
Blood stasis (stagnant)
• In the absence of injury, stasis and slow flowing blood encourage
platelet aggregation and a thrombus/clot is formed.

43. Once a thrombus breaks, it is
carried away in blood to a distant
site where it would
cause complete or partial
obstruction.

44. Types of Embolism
• Fat Embolism
Miroscopic fat globules may be found in the circulation after fracture of
long bones (which have fatty marrow)
• Air Embolism
Gas bubbles within circulation can obstruct vascular flow and, cause
distal ischemic injury almost as readily as thrombotic masses.

45. ISCHAEMIA
Ischaemia:
Ischaemia is a condition of inadequate blood supply to an area of the
body.
Ischaemia may be partial or complete. Complete ischaemia is likely to
result in an infarct, which is a localized area of ischaemic necrosis.
Hypoxia (too little ) or anoxia (no oxygen) is the most consequences of
ischaemia to a part.
Remember!!! Hypoxia and anoxia are very important causes of cell
injury and cell death.
Types of hypoxia….P19

46. Causes of ischaemia:
•Failure of arterial supply
•Venous obstruction. This leads to stoppage of blood return to the heart and,
hence, prevention of arterial blood supply to that part
•Small vessel obstruction may cause micro-infarction.
• Vasculitis is another examples.
• Angina pectoris is an example where chest pain occurs on exertion when
degenerate coronary arteries cannot increase the blood flow sufficiently to
meet the added demand by the heart muscle.

47. Oedema
• Definition: It is an excessive accumulation of extracellular fluid in the intercellular
(interstitial) tissue spaces or body cavities. It may be localized or generalized.
• Oedema can be the result of poor venous and lymphatic return of fluid from the tissues,
result of protein malnutrition and inflammation resulting from tissue injury.
Forms of oedema….P27 E.g. Severe generalized oedema – anasarca, e.g in renal/kidney
failure, kwashiorkor (malnutrition syndrome of children).
Predisposing factors:
•An increase in the hydrostatic pressure within the vessels.
•A decrease in the colloid osmotic pressure within the vessels, (e.g due to low protein
concentration in plasma).
•Changes in fluid balance (with increased extracellular fluid and plasma volume).
•Increased vascular permeability for example due to surface endothelial molecules and
prostaglandins.
•Lymphatic obstruction, usually local

48. 6
Hyperemia and Congestion
HYPEREMIA I.
• Definition: locally
increased blood volume
• Forms: active,
passive/congestion
• ACTIVE HYPEREMIA
– Active dilation of
arteriae, arterioles,
capillaries
– erythema
– Forms: physiological,
pathologic (inflammation,
fever, chemical and
physical injury)

49. HYPEREMIA II.
• PASSIVE HYPEREMIA
(congestion)
– dilation of venous side due to
decreased outflow
– cyanosis, hypoxia
– Causes:
• Systemic: congestive heart
failure
• Local: thrombosis, obstruction
– Deep venous thrombosis-legs
– Pylethrombosis- portal
congestion
– V.cava sup. syndrome
49

50. Congestion
Congestion – a condition where there is reduced venous drainage
giving rise to what is called passive congestion. Blood flow is slowed
and the part becomes stuffed with slow moving blood, giving a reddish
purple colour to the area.
The part becomes more bluish purple as there is an increase of
deoxygenated haemoglobin in the blood, a condition known as
cyanosis.

51. THE PATHOLOGICAL EFFECTS OF CONGESTION
i. Severe venous congestion may lead to escape of fluid from circulation
to the tissues (oedema) or even escape of red cells (haemorrhage).
ii. The resultant anoxia leads to increased vascular permeability, leading
to oedema.
iii. In the lungs particularly, congestion is likely to be accompanied by
oedema and small haemorrhages because the lung capillaries and
venules are particularly thin- walled, poorly supported and susceptible
to hypoxia.

53. HAEMORRHAGE
Haemorrhage- the escape of blood from vessels within the circulatory
system and implies that there has been damage to the integrity of the vessel
in some way.
If the haemorrhage is too severe to be compensated for by these
mechanisms a state of
haemorrhagic shock ensues:
• Despite increased heart rate and selective peripheral vasoconstriction
• Blood pressure drops
• There is diminished blood flow to the tissues and ischaemic damage
may result, particularly in susceptible tissues such as the brain and the
kidneys.

54. SHOCK
Almost all types of shock can be defined as a state of circulatory failure
resulting from some stress leading to inadequate cellular perfusion and an
oxygen deficit in the tissues.
The term shock can be regarded as a clinical description of a patient who
• is pale, has a cold clammy skin (‘a cold sweat’) with a rapid thready
pulse,
• low blood pressure and rapid respiration.
• cyanosis may be noted
• the temperature may be subnormal.
• little or no urine is passed.
• the patient is still and apathetic, and;
• if the shocked condition is not relieved, may become confused,
comatosed and then die.

55. Types of shock:
Causes of death in shock
In the early stages death can result from circulatory collapse, causing:
• Cerebral ischaemia
• Heart failure
At progressive stages, death may result from:
• Lactic acidosis and electrolyte disturbance
• Pulmonary oedema
• Acute tubular necrosis and renal failure.
Distributive Shock
Generalised Vesodialation e.g bacterial
Infection
Cardiogenic Pump/Heart failure, Myocardial infarction
Obstructive Shock Pulmonary Obstruction (blood can not go
into the lungs)

56. Disorders of Carbohydrate Metabolism
Physiologic remarks:
Carbohydrates are present in food in various forms:
1. simple sugars - monosaccharides
2. complex chemical units - disaccharides
- polysaccharides
Processing of carbohydrates in GIT
Ingested carbohydrates -cleaving process-monosaccharides- absorption in
the stomach, duodenum and proximal jejunum
https://www.osmosis.org/learn/Disorders_of_carbohydrate_metabolism:_P
athology_review

57. Disturbances in Carbohydrate Resorption
Disaccharidase deficiency syndrome
saccharase = enzyme which hydrolyses disaccharide
saccharose (to fructose and glucose)
lactase = enzyme which splits disaccharide lactose
(to glucose and galactose)
maltase = enzyme which splits disaccharide maltose
(to two molecule of glucose)
a) Activity of disaccharidase is decreased
Decreased hydrolysis of disaccharide-decreased resorption of substrate- increased
concentration of disaccharide in small intestine lumen-increased osmotic activity of the
lumen fluid-diarrhea
b) Activity of disaccharidase is increased
Increased concentration of disaccharide in small intestine lumen-increased
concentration of disaccharide in large intestine-disaccharide fermentation by bacteria-
increased concentration of lactic acid and fatty acids-stimulation of intestine wall-
abdominal cramps, bloating, diarrhea, acidic stools, explosive diarrhea.

58. Lactase deficiency syndrome
Causes of lactase deficiency:
- genetic defect (primary)
- secondary to a wide variety of gastrointestinal diseases that damage the
mucosa of the small intestine (secondary- ulcerative colitis; viral and
bacterial infections of the intestinal tract; etc.)
Disaccharide lactose is the principal carbohydrate in milk.
- Many persons showing milk intolerance prove to be lactase – deficient
- Primary lactase deficiency incidence is as high as 80 % to 90 % among
African - Americans, Asians, and Bantus population
- Milk intolerance may not become clinically apparent until
adolescence

59. Glycogenosis (glycogen storage disease)
Autosomal recessive disease (inborn errors of metabolism, emzymopathy)
Here: there are defects in degradation of glycogen.
The disturbances result in storage of abnormal glycogen, or storage of
abnormal amount of glycogen in various organs of the body
Example: Hepatorenal glycogenosis (Morbus von Gierke)
Cause: Deficit of glucose-6-fosfatase in liver and kidney
Results: Hypoglycemia in fasting individuals, hyperlipemia,
ketonemia

60. Diabetes
Type 1 diabetes is an autoimmune disease. It occurs when the immune
system attacks and destroys the beta cells in the pancreas so that they
can no longer produce insulin. The exact cause remains unknown, but it
may be due to genetic and environmental factors, including viruses.
Type 2 diabetes begins when the body’s muscle, fat, and liver cells
become unable to process glucose. The pancreas reacts by producing
extra insulin, but in time, it cannot produce enough insulin. The body
can no longer control blood glucose levels.
Other problems that can occur include:
• Exocrine pancreatic insufficiency (EPI): The pancreas does not
produce enough enzymes
• Pancreatic cysts: These can be removed by surgery if there is a
risk of cancer

61. Regulation of the blood glucose level depends on liver
1. extracting glucose from blood
2. synthesizing glycogen
3. performing glycogenolysis
4. performing gluconeogenesis
To a lesser extent peripheral tissues (muscle and adipocytes) use glucose for their
energy needs, thus contributing to maintenance of normal blood glucose level.
Note: The livers uptake and output of glucose and the use of glucose by peripheral
tissues depend on the physiologic balance of several hormones that:
1. lower blood glucose level - insulin
2. rise blood glucose level - glucagon, epinephrine, GH,
glucocorticoids...

62. Introduction to Disorders of Growth: Tumors
First: ‘Neoplasia (nee-oh-PLAY-zhuh) is the uncontrolled, abnormal growth of cells
or tissues in the body, and the abnormal growth itself is called a neoplasm (nee-oh-
PLAZ-m) or tumor’.
Overview:
Cancer/Tumour refers to any one of a large number of diseases characterized by
the development of abnormal cells that divide uncontrollably and have the ability
to infiltrate and destroy normal body tissue. Cancer often has the ability to spread
throughout your body.
Symptoms:
Signs and symptoms caused by cancer will vary depending on what part of the body
is affected.
Some general signs and symptoms associated with, but not specific to, cancer,
include:
• Fatigue; Lump or area of thickening that can be felt under the skin
• Weight changes, including unintended loss or gain; Skin changes, such as
yellowing, darkening or redness of the skin, sores that won't heal, or changes to
existing moles.

63. Causes:
Cancer is caused by changes (mutations) to the DNA within cells. The DNA inside a cell is
packaged into a large number of individual genes, each of which contains a set of
instructions telling the cell what functions to perform, as well as how to grow and divide.
Errors in the instructions can cause the cell to stop its normal function and may allow a
cell to become cancerous.
What do gene mutations do?
A gene mutation can instruct a healthy cell to:
• Allow rapid growth. A gene mutation can tell a cell to grow and divide more
rapidly. This creates many new cells that all have that same mutation.
• Fail to stop uncontrolled cell growth. Normal cells know when to stop growing so
that you have just the right number of each type of cell. Cancer cells lose the controls
(tumor suppressor genes) that tell them when to stop growing. A mutation in a tumor
suppressor gene allows cancer cells to continue growing and accumulating.
• Make mistakes when repairing DNA errors. DNA repair genes look for errors in a
cell's DNA and make corrections. A mutation in a DNA repair gene may mean that other
errors aren't corrected, leading
https://www.youtube.com/watch?v=GhfrHjBX5eA

64. What causes gene mutations?
Gene mutations can occur for several reasons, for instance:
•Gene mutations you're born with. You may be born with a genetic mutation that you inherited from your
parents. This type of mutation accounts for a small percentage of cancers.
•Gene mutations that occur after birth. Most gene mutations occur after you're born and aren't inherited. A
number of forces can cause gene mutations, such as smoking, radiation, viruses, cancer-causing chemicals
(carcinogens), obesity, hormones, chronic inflammation and a lack of exercise.
What is a tumor?
A tumor develops when cells reproduce too quickly.
Tumors can vary in size from a tiny nodule to a large mass, depending on the type, and they can appear
almost anywhere on the body.
There are three main types of tumor:
Benign: These are not cancerous. They either cannot spread or grow, or they do so very slowly. If a doctor
removes them, they do not generally return.
Premalignant: In these tumors, the cells are not yet cancerous, but they have the potential to become
malignant.
Malignant: Malignant tumors are cancerous. The cells can grow and spread to other parts of the body.
It is not always clear how a tumor will act in the future. Some benign tumors can become premalignant and
then malignant. For this reason, it is best to monitor any growth.
Diagnosis:
Mmammogram or an MRI. However, these tests can only detect whether a lump is present.
A biopsy is necessary to determine the type of lump.

65. Q:
Do all cancers involve a tumor?
A:
Yes, all cancers involve some form of solid or liquid
tumor. In general, a tumor is a swollen mass of
tissue that arises from the uncontrolled division of
cells.
In addition to being either malignant or benign,
tumors can be either solid or liquid. Solid tumors
get their names, such as sarcomas, carcinomas,
and lymphomas, from the type of cell that forms
them. In solid tumors, the mass of tissue does not
include liquid areas or cysts. Some types of cancer,
for example, leukemia, which is cancer of the
blood, do not form solid tumors.
CARCINOGENESIS:
The process by which normal, healthy cells
transform into cancer cells is termed
carcinogenesis or oncogenesis. The development
of a malignant tumour in otherwise healthy tissue
is the result of a complex series of events
beginning with a single cell that has acquired
malignant properties through cellular DNA damage