This document discusses hemodynamic disorders and edema. It begins by defining the normal composition of body water and the three body compartments it is contained in. It then defines edema as excess fluid in the interstitial tissue space and describes different types of edema based on location. The pathophysiology of edema involves either increased hydrostatic pressure or reduced plasma osmotic pressure. Specific causes of edema are discussed like congestive heart failure, liver disease, and malnutrition. The document also covers morphology, hemorrhage, congestion, hemostasis, and hemorrhagic disorders.

1. Hemodynamic disorder - 1
Dr. Bahoran Singh

2. Normal body composition
• Water composes about 60% of total body
mass
• 3 body compartments containing H2O:
– Intracellular = 70%
– Interstitial = 25%
– Plasma = 5%

3. Edema
• it is increased fluid in interstitial tissue space.
• When the fluid is deposited in cavities it is
called as effusion.
• Hydrothorax is edema in the thoracic cavity.
Hydropericardium is edema in the pericardial
cavity, and hydroperitoneum is edema in the
peritoneum.

4. Pathophysiology of Edema
•  Two opposing major factors governing
fluid movement between vascular and
interstitial space:

5. • 1. Increase in hydrostatic pressure
• Caused due to impair venous return
• Localized- deep venous thrombosis
• Systemic- Congestive cardiac failure
• 2. Reduced Plasma Osmotic Pressure
• Mainly due to albumin
• causes- Reduced albumin synthesis- liver
diseases and PEM
• Excess loss

6. Pathophysiologic Categories of Edema
• Increased Hydrostatic Pressure
Impaired Venous Return
Congestive heart failure
Constrictive pericarditis
Ascites (liver cirrhosis)
Venous obstruction or compression
Thrombosis
External pressure (e.g., mass)
Lower extremity inactivity with prolonged
dependency
• Arteriolar Dilation
• Heat
Neurohumoral dysregulation

7. )• 2. Reduced Plasma Osmotic Pressure
(Hypoproteinemia
• Protein-losing glomerulopathies (nephrotic
syndrome)
Liver cirrhosis (ascites)
Malnutrition
Protein-losing gastroenteropathy
• 3. Lymphatic Obstruction
• Inflmmatory
Neoplastic
Postsurgical
Postirradiation

8. • 4. Sodium Retention
• Excessive salt intake with renal insuffiiency
• Increased tubular reabsorption of sodium
• Renal hypoperfusion
• Increased renin-angiotensin-aldosterone
secretion
• 5. Inflmmation
• Acute inflmmation
• Chronic inflmmation
• Angiogenesis

9. Mechanisms of systemic edema in heart failure, renal failure,
malnutrition, hepatic failure, and nephrotic syndrome.

10. Types of edema
• Transudate:
• protein poor (<3 gm/dl) fluid with specific gravity
of <1.012 due to imbalances in normal
hemodynamic forces e.g. congestive heart failure,
liver and renal disease etc.
• Exudate -
• protein rich (>3 gm/dl) fluid with a specific gravity
of >1.020 results from endothelial damage and
alteration of vascular permeability e.g.
inflammatory and immunologic pathology

11. MORPHOLOGY
• Easily recognized grossly and microscopically
• Gross- Subcutaneous edema- In region of
high hydrostatic pressure, influenced by
gravity so called dependent edema.
• Pitting edema
• Renal dysfunction- appears initially in parts of
the body containing loose connective tissue
• eg Periorbital edema

12. • Pulmonary edema-
• lungs are often two to three times their
normal weight,
• sectioning yields frothy, blood-tinged flid—a
mixture of air, edema, and extravasated red
cells.
• Brain edema- narrowed sulci and distended
gyri

13. Hyperemia & Congestion
• Hyperemia –
• Active process resulting from increased tissue blood
flow because of arteriolar dilation,
• e.g. skeletal muscle during exercise or at sites of
inflammation.
• The affected tissue is redder because of the
engorgement of vessels with oxygenated blood.

14. Congestion
• Passive process resulting from impaired
outflow from a tissue.
• It may be systemic e.g. cardiac failure, or local
e.g. an isolated venous obstruction.
• The tissue has a blue-red color (cyanosis), due
to accumulation of deoxygenated hemoglobin
in the affected tissues

16. CONGESTION
Chronic congestion Raised venous pressure
Anoxia
Metabolite accumulation Enlarged interendothelial gap
Base membrane degeneration
Parenchymal Interstitial fibrosis
Atrophy Reticular fiber collapsed Increase permeability
Degeneration Collagen increased
Necrosis Fibroblast proliferation
Microscopic scarring
Edema Hemorrhage
Congestive sclerosis

17. Liver with chronic passive congestion and hemorrhagic necrosis. A, Central areas
are red and slightly depressed compared with the surrounding tan viable
parenchyma, forming a “nutmeg liver” pattern (so-called because it resembles the
cut surface of a nutmeg).

18. Centrilobular necrosis with degenerating
hepatocytes and hemorrhage and
hemosiderin laden macrophages

19. Lung:
Acute pulmonary congestion
Gross: Plump swollen lung with
shining pleura, edematous fluid
flowing out while cutting the
lung
LM:
Alveolar capillaries highly dilated
(rosary- like appearance) and
engorged with blood
Alveolar cavity filled with eosinophilic
edema fluid
Manifestation
Pink colored foamy sputum

20. CONGESTION
– Lung:
– Chronic pulmonary congestion
– Gross: Hard, with brown spots
scattered
• —— Brown induration
– LM:
– Septa thickened and fibrosis
• Alveolar spaces containing ‘heart
failure cells’— hemosiderin-laden
macrophages
•
• Manifestation
• Rusty sputum, dyspnea, etc.

21. HEMOSTASIS
• Normal hemostasis comprises a series of regulated
processes that maintain blood in a fluid, clot-free state
in normal vessels while rapidly forming a localized
hemostatic plug at the site of vascular injury.
- Normal Hemostasis :
• Transient arteriolar vasoconstriction
• Primary haemostasis
• Tissue factor
• Secondary haemostasis
• Counter regulatory mechanisms

22. Hemostasis
• Arteriolar vasoconstriction-
• occurs immediately and
markedly reduces blood
flow
• Mediated by reflex
neurogenic mechanism
• Augmented by endothelin.
• It is transient.

23. • Primary hemostasis
and platelets plug
formation
• endothelium disruption
exposes subendothelial
von Willebrand
factor(vWF) and
collagen
• Promotes plateletes
activation and adhesion

24. Secondary hemostasis- deposition of
fibrin
• exposure of tissue factor at
the site of injury leads to
activation factor VII and
culminate in thrombin
generation.
• Thrombin cleaves
circulating fibrinogen into
insoluble fibrin, creating a
fibrin meshwork

25. Clot stabilization and resorption
• Permanent plug
formation occur by
contraction of
polymerized fibrin
platelets aggregates.
• Activation of counter
regulatory mechanism
(t-PA) that limit clotting
and leads to clot
resorption and tissue
repair.

26. Prothrombotic Properties :
- Platelet effects :
• Endothelial injury brings platelets into contact
with the subendothelial ECM, which includes
among von Willebrand factor (vWF), a large
multimeric protein that is synthesized by EC.
• vWF is held fast to the ECM through interactions
with collagen and also binds tightly to Gp1b, a
glycoprotein found on the surface of platelets.
• These interactions allow vWF to act as a sort of
molecular glue that binds platelets tightly to
denuded vessel walls .

27. Platelets
• Have critical role in hemostasis by forming the
primary plug and by providing a surface that
binds and concentrates activated coagulation
factors.
• their function depends on several glycoprotein
receptors, a contractile cytoskeleton and
granules.
• Two types of cytoplasmic granules are present in
platelets – 1. ά granules 2. Dense(δ) granules

28. • ά granules- have
• Adhesion molecule P- selectin
• Proteins involved in coagulation such as
fibrinogen, Factor V, and vWF.
• Protein involved in wound healing
– fibronectin
– platelet factor 4( a heparin-binding chemokines)
– PDGF
– TGF-ẞ
• Dense granules contain ADP, ATP, ionised
calcium, serotonin and epinephrine.

29. Platelets plug formation
• Platelet adhesion-
• Mediated via interaction with vWF
• vWF acts as bridge between GpIb( platelet
surface receptor and exposed collagen.
• deficiencies of either vWF (von Willebrand
disease) or GpIb (Bernard- Soulier syndrome)
result in bleeding disorder.

30. • Change in platelets shape – smooth disc to
spiky “sea urchins”
• increase in surface area and alteration in
GpIIb/IIIa that increase affinity for fibrinogen
and by the translocation of negatively charged
phospholipids ( phosphatidylserine) to the
platelets surface

31. • Platelets secretion (release reaction ) of granule
contents occurs along with changes in shape;
often referred to together as platelet activation.
• Thrombin activate platelets through G-protein
coupled receptor referred as protease -activated
receptor (PAR) which is switched on by a
proteolytic cleavage carried out by thrombin.
• ADP causes additional activation of platelets this
is called recruitment.
• Activated platelets release thromboxane
A2(TxA2) an inducer of platelets

32. PLATELET AGGREGATION
• following activation there is conformational
change in GpIIb/IIIa allow binding of fibrinogen
form bridge between adjacent platelets
• Inherited deficiency og GpIIb/IIIa results in
Glanzmann thromboasthenia.
• Initial aggregation is reversible.
• concurrent activation of thrombin stabilizes
platelet plug by further platelet activation and
aggregation and by promoting irreversible
platelet contraction.

33. Platelet adhesion and aggregation.

34. Coagulation cascade
• The coagulation cascade is series of amplifying
enzymatic reaction that leads to deposition of
insoluble fibrin clot.

35. Coagulation Cascade

36. Role of thrombin in hemostasis and
cellular activation

37. Factors that limit Coagulation
• Fibrinolytic system

38. Anticoagulant activities of normal
endothelium

39. • The normal flow of liquid blood is maintained
by endothelial antiplatelet, anticoagulant and
fibrinolytic properties.
• After injury or activation, endothelium
exhibits several procoagulant activities.
• Endothelial cells are central regulators of
hemostasis; the balance between the anti-
and prothrombotic activities of endothelium
determines whether thrombus formation,
propagation, or dissolution occurs.

40. Antithrombotic properties :
• Antiplatelet effects :
• Intact endothelium prevents platelets (and
plasma coagulation factors) from engaging the
highly thrombogenic subendothelial ECM.
• Nonactivated platelets do not adhere to
normal endothelium; even with activated
platelets, prostacyclin (i.e., prostaglandin I2
[PGI2]) and nitric oxide produced by
endothelium impede their adhesion.

41. • Even if platelets are activated after focal
endothelial injury, they are inhibited from
adhering to the surrounding uninjured
endothelium by endothelial prostacyclin and
nitric oxide.
• Endothelial cells also produce adenosine
diphosphatase, which degrades adenosine
diphosphate (ADP) and further inhibits platelet
aggregation.

42. • 2. Anticoagulant effects :
• These actions are mediated by factors expressed
on endothelial surfaces, particularly heparin-like
molecules, thrombomodulin, endothelial protein
C receptor and tissue factor pathway inhibitor .
• The heparin-like molecules act indirectly: They
bind and activate antithrombin III , which then
inhibit thrombin and factors
IXa, Xa, XIa, and XIIa.

43. • Thrombomodulin also acts indirectly: It binds to
thrombin, thereby modifying the substrate
specificity of thrombin, so that instead of cleaving
fibrinogen, it instead cleaves and activates
protein C, an anticoagulant.
• Endothelium is also a major synthetic source for
tissue factor pathway inhibitor, a cell-surface
protein that complexes and inhibits activated
tissue factor – factor VIIa and factor Xa
molecules.

44. • 3. Fibrinolytic effects :
• Endothelial cells synthesize tissue type
plasminogen activator(t- PA) , promoting
fibrinolytic activity to clear fibrin deposits
from endothelial surfaces.

45. Hemorrhagic Disorders
• Disorders associated with abnormal bleeding
inevitably stem from primary or secondary
defects in vessel walls, platelets, or
coagulation factors.
• 1. Defects of primary hemostasis (platelet
defects or von Willebrand disease)
• present with small bleeds in skin or mucosal
membrane it may be petechiae(1-2 mm) or
Purpura slightly larger( ≥3 mm)than peteciae

46. • Mucosal bleeding associated with defects in
primary hemostasis may also take the form of
• epistaxis(nosebleeds),
• gastrointestinal bleeding, or
• excessive menstruation (menorrhagia).
• Or Intracerebral hemorrhage.

47. Punctate petechial hemorrhages of
the colonic mucosa Fatal intracerebral bleed

48. Defects of secondary hemostasis
(coagulation factor defects)
• present with bleeds into soft tissues (e.g.,
muscle) or joints (hemarthrosis).
• Hemarthrosis following minor trauma is the
characteristic of hemophilia

49. • Generalized defects involving small vessels
• present with “palpable purpura” and ecchymoses
.
• Ecchymoses (bruises)
• Hemorrhage of 1-2 cm in size
• There is formation of hematoma due to
extravasation of blood.
• these are characteristic of systemic disorders that
disrupt small blood vessels (vasculitis) or lead to
blood vessel fragility ( Amyloidosis and scurvy