brief lecture notes for 5th sem MBBS, on portal hypertension and varices. Introduction to portal hypertension and esophageal and gastric varices and management of variceal bleeding.

1. Hepatology lectures for
5th Sem;MBBS
Pratap Sagar Tiwari
MBBS,MD (Medicine),DM (Hepatology)

2. Summary
? Predisposing
conditions
Etiologies
Liver Fibrosis/cirrhosis
Portal Hypertension
Varices
Splenomegaly
Ascites
Normal Liver

3. Portal Hypertension
Pratap Sagar Tiwari
Total slides : 44
3

4. CONTENT
What is PHTN ?
1
Complications ?
2
What are Varices ?
3
Acute Variceal Bleeding
4

5. 5
Structural & vascular

6. NOTE: CAPILLARIZATION OF THE SINUSOIDS
• LSECs can be defined as a unique microvascular cell type that differs morphologically
and functionally from capillary endothelial cells due to the presence of the typical
fenestrations and absence of the basement membrane.
As a response to liver injury LSECs lose the fenestrations, form a continuous basal membrane, and acquire pro-
inflammatory, and pro-fibrotic features.
➢act as a selectively barrier between the blood and liver parenchyma. The LSECs by
means of expression of scavenging receptors, together with extremely effective
endocytic capacity, in few minutes can remove and recycle materials from the
circulation, such as viral particles, advanced glycation end products and lipids.
➢act as important mediators of lymphocyte adhesion and migration across the
sinusoidal endothelium into the parenchyma.
➢maintain hepatic stellate cells quiescence, preventing liver fibrosis development.

7. 7
Structural & vascular

8. Portal Hypertension
↑ IHR
↑ Portal Pressure
↑ portal venous
inflow
x

9. Arterial vasodilation in the peripheral and splanchnic circulation
Decrease in central blood volume
“relative arterial hypovolemia”
stimulation of cardiopulmonary volume
receptors and arterial baroreceptors
SNS
Activation of Neurohumoral responses
RAAS AVP
• Mediators from these systems result in sodium and water
retention by the kidneys, and consequently, plasma volume
expansion.
➢ Sodium retention is due to increased tubular reabsorption of
sodium, mediated by receptors for aldosterone, angiotensin
and alpha-adrenergic stimuli.
➢ The decrease in water excretion is due to increased secretion
of antidiuretic hormone.
Thus the hyperdynamic state is created.
It is the combination of arterial
vasodilation and blood volume expansion
that produces optimal conditions for
maintaining the hyperdynamic circulatory
state in PHTN.
Pts with cirrhosis typically present with a characteristic hyperdynamic circulation with an ↑ed CO, ↑ed HR, and low SVR
and low arterial BP.

10. MEASURING PORTAL PRESSURE
(PP)
• Direct measurement of PP by puncturing the PV is
an inconvenient and invasive technique.
• It is a/with surgical and hemorrhagic risk, and severe
complications such as portal vein thrombosis,
hemoperitoneum, hematoma, hemobilia, and
intrahepatic arteriovenous fistulae.
• Therefore, in clinical practice PP is determined
indirectly by measuring wedged hepatic venous
pressure (WHVP), assuming that WHVP correlates
closely with sinusoidal pressure/portal pressure.

11. PORTAL HYPERTENSION (PHTN)
• PHTN indicates increased pressure in portal venous
system. Normal portal venous pressure is 10 mmHg
(14 cm of H2O).
• In clinical practice, HVPG is a surrogate marker of
portal pressure gradient and is derived from WHVP
corrected (subtracted) with free hepatic venous
pressure (FHVP).
HVPG=WHVP – FHVP
(normal HVPG: 1-4 mm Hg).
An HVPG of ≥5 mmHg defines PHTN, and if the
measurement >10 mmHg it is called clinically
significant portal hypertension (CSPH).

12. PHTN FEATURES & ITS COMPLICATIONS

13. PHTN FEATURES & ITS COMPLICATIONS
Splenomegaly Splenomegaly is a cardinal finding and a diagnosis of
PHTN is unusual when splenomegaly cannot be detected
clinically or by USG.
The spleen is rarely enlarged >5 cm below the left costal
margin in adults but more marked splenomegaly can occur in
childhood and adolescence.
PHTN → ↑ Congestion → Tissue hyperplasia and fibrosis → f/o Hypersplenism
↑ portal pressure  ↑ blood flow  Splenomegaly due to any cause

14. PHTN FEATURES & ITS COMPLICATIONS
Ascites
Varices
Splenomegaly
Portosystemic Anastomosis
Once PHTN ensues, in an attempt to decompress the rising PP
there is development of porto-systemic collateral formation.
Two basic mechanisms lead to:
(1) neo-angiogenesis
(2) dilatation of pre-existing embryonic channels between portal and
systemic circulations.
• The more severe and more prolonged the PHTN, the higher are
the number of portosystemic pathways.
• However, this traditional hypothesis has been challenged and it
has been suggested that the formation of portosystemic collateral
circulation may be due in part to angiogenesis driven by VEGF.

15. UMBILICAL VARICES
The Paraumbilical veins (inferior veins of Sappey) accompany
ligamentum teres (obliterated left UV) in the Falciform ligament and
connect anterior parietal veins (superior and inferior epigastric veins
in the rectus sheath and thoracoepigastric vein in subcutaneous tissue)
at umbilicus with left branch of PV.
Paraumbilical veins connected with numerous subcutaneous vessels
of the anterior abdominal wall, create a ‘‘caput medusae’’ pattern.
Pic src:https://pt.slideshare.net/sinless/portal-1813309
The normally obliterated umbilical vein; left, which lies in the ligamentum
teres (round ligament), is recanalized with increases in hepatic sinusoidal
pressure and connects the left portal vein to systemic veins around the
umbilicus. These veins then drain into the epigastric vessels and appear as
caput medusae.
Reference: Zakim & Boyer hepatology. 6th edition
15
Rarely, a large umbilical collateral vessel has a blood flow sufficient to give a venous hum on auscultation
(Cruveilhier–Baumgarten syndrome).

16. PORTOSYSTEMIC
COLLATERALS VESSELS (PSCV)
• The PV drains blood from the small and large
intestines, stomach, spleen, pancreas, and
gallbladder.
• The SMV and the SV unite behind the neck of the
pancreas to form the PV.
• The left gastric vein (formerly, gastric coronary vein), which runs along the lesser
curvature of the stomach, receives distal esophageal veins, which also enlarge in
PHTN forming Gastroesophageal varices.

17. CLASSIFICATION OF COLLATERAL PATHWAYS
• The simplest classification of PSCV puts esophagogastric varices into one group and
all other varices as ectopic varices. [1]
• Ectopic varices are defined as large PSCV occurring anywhere in the GI tract other
than the esophagogastric region. [2] and constitute 1-5% of all variceal bleeds in
patients with intrahepatic PHTN and 20-30% of those with extrahepatic PHTN.[3,4]
1. Norton ID, Andrews JC, Kamath PS. Management of ectopic varices. Hepatology. 1998;28:1154–1158.
2. Kinkhabwala M, Mousavi A, Iyer S, Adamsons R. Bleeding ileal varicosity demonstrated by transhepatic portography. AJR Am J Roentgenol 1977; 129: 514-516
3. Lebrec D, Benhamou JP. Ectopic varices in portal hypertension. Clin Gastroenterol 1985;14:105–121.
4. Norton ID, Andrews JC, Kamath PS. Management of ectopic varices. Hepatology 1998;28:1154–1158.
17

18. ESOPHAGEAL VARICES
Modified Paquet classification
• Grade I: Varices extending just above the mucosal level and compression with air
insufflation
• Grade II: Varices extending above the mucosal level (with no compression when air is
insufflated) up to one-third of the luminal diameter.
• Grade III: Varices extending for more than 50% of the luminal diameter, or touching.
• Recent consensus from the American Association for the Study of Liver Diseases (AASLD) includes a
recommendation to simplify this using 2 grades i.e. small and large with a cut-off size of 5 mm.
• As a consequence, all the recommendations for large varices will apply also to medium varices for centres using
the 3-grade classification.
18

19. Examples of GRADE I
Varices extending just above the mucosal level and
compression with air insufflation.
19

20. Examples of GRADE II
Varices extending above the mucosal level (with no compression
when air is insufflated) up to one-third of the luminal diameter.
20

21. Examples of GRADE III
Varices extending for more than 50% of the luminal diameter, or
touching.
21

22. Gastric Varices
Sarin’s classification [1], which divides the GV into gastro-
oesophageal (GOV) and isolated gastric varices (IGV).
GOV are basically oesophageal varices that extend beyond the
esophagogastric junction and are further subdivided into
• GOV1, which extend for 2–5 cm along the lesser curvature
• GOV2, which extend along the fundus.
IGV, as the name suggests, are not associated with esophageal
varices and are divided into
• IGV1, which are located in the fundus, and
• IGV2, present anywhere other than the fundus including the
body, antrum or pylorus.
1. Sarin SK, Lahoti D, Saxena SP et al (1992) Prevalence, classification and natural history of gastric varices: a long-term follow up study in 568 portal hypertension patients. Hepatology 16:1343–1349
22

23. EXAMPLES OF RED SIGNS/ RED WALE SIGNS
• These are red patches or
strips on the varices, as a sign
of an increased risk of
bleeding,
Any varices with red signs or
large varices are tagged as
HIGH RISK VARICES.
23

24. COMMON PORTOSYSTEMIC COLLATERALS
Collaterals Afferent Efferent
Esophageal varices Left gastric vein Azygous-hemiazygous vein
Gastric varices Anterior branch of LGV (GOV1)
Short gastric and Posterior gastric veins
(GOV2)
Esophageal and paraesophageal
veins
Paraumbilical vein Left portal vein Anterior abdominal wall veins and
iliofemoral veins
Rectal varices Superior rectal vein Middle/inferior rectal veins

25. NOTE: VARICES
• Gastroesophageal varices are present in approx
50% of pts with cirrhosis.
• Their presence correlates with the severity of
liver disease ; while only 40% of Child A pts
have varices, they are present in 85% of Child C
patients.
• Gastric varices are less prevalent than
esophageal varices and are present in 5%-33%
of patients with PHTN with a reported incidence
of bleeding of about 25% in 2 years, with a
higher bleeding incidence for fundal varices.

26. NOTE: RECTAL VARICES
Superior rectal vein
Internal pudendal V
Inferior Mesenteric V
Inferior rectal vein
Middle rectal vein Internal Iliac V Ext Iliac V
Common Iliac V
Inferior Vena Cava
Rectal Varices
Afferents to Rectal Varices: IMV continues as
the superior rectal vein and acts as afferent to
rectal varices.
Efferents from Rectal Varices: middle and
inferior rectal veins of the iliac system.
26

27. SELF- ASSESSMENT
Causes of Upper GI bleed
1
Causes of Portal hypertension
2
Child pugh classification
3
Portal Hypertensive Gastropathy
4

28. CAUSES OF UGIB

29. CHILD PUGH CLASSIFICATION

30. PORTAL HYPERTENSION- CAUSES
PREHEPATIC INTRAHEPATIC POST-HEPATIC
PRESINUSOIDAL SINUSOIDAL POST-SINUSOIDAL
Portal vein thrombosis
Splenic vein thrombosis
Arteriovenous fistula
EHPVO
Splenomegaly
Schistosomiasis
Primary biliary cholangitis
Sclerosing cholangitis
Lymphoma
Sarcoidosis
Congenital hepatic fibrosis
Toxic-vinyl chloride
Sinusoidal fibrosis
Alcoholic hepatitis
Drugs (MTX, Amiadarone)
Toxin (vinyl chloride, copper)
Metabolic (NASH, Gaucher’s)
Amyloidosis
Nodular regenerative
hyperplasia
Polycystic liver disease
Hypervitaminosis A
Veno-occlusive
disease
Hypervitaminosis A
Budd-chiari syndrome
Congestive heart failure
Constrictive pericarditis
Tricuspid valve disease

31. PROPHYLAXIS NEEDED ?
• Patients with compensated cirrhosis will typically develop varices at a rate of 7 to 8%
/yr.[1]
• In addition, individuals with SEV have progression to LEV at a rate of 10 to 12%
/yr.[2]
• It is important to decrease the risk of variceal hemorrhage, which occurs at a rate of
approx 10 to 15% /yr;
• The highest rates of hemorrhage occur with LEV, decompensated cirrhosis, or
RCS.[3,4]
1. Groszmann RJ, Garcia-Tsao G, Bosch J, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med. 2005;353:2254-61.
2. Merli M, Nicolini G, Angeloni S, et al. Incidence and natural history of small esophageal varices in cirrhotic patients. J Hepatol. 2003;38:266-72.
3. D’Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis. 1999;19:475-505.
4. North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N Engl J
Med. 1988;319:983-9.

32. PROPHYLAXIS OF VARICEAL HEMORRHAGE (VH)
PHTN / No VARIX
Prevention of the
development of varices
in pts with PHTN
Preprimary Prophylaxis
H/o VH
VH prevention measures
for pts with a known
H/o VH
Secondary Prophylaxis
VARIX / NO VH
Prevention of VH in pts
with known esophageal
varices, but no history of VH
Primary Prophylaxis

33. PROPHYLAXIS OF VARICEAL HEMORRHAGE (VH)
PHTN / No VARIX
Prevention of the
development of varices in pts
with PHTN
Preprimary Prophylaxis
• For pts with cirrhosis and clinically significant
portal hypertension (HVPG ≥10 mm Hg), but no
evidence of varices on EGD, preprimary
prophylaxis is not recommended for
the prevention of varices.[3]
• For individuals with compensated cirrhosis and
absence of varices, the focus should be to eliminate
the cause of liver disease and prevent clinical
decompensation.[3]

34. PROPHYLAXIS OF VARICEAL HEMORRHAGE (VH)
VARIX / NO VH
Prevention of VH in pts
with known esophageal
varices, but no history of VH
Primary Prophylaxis

35. HOW BB WORKS ?
• via β1-adrenergic blockade, reduce heart rate and cardiac output with a decrease in
flow of about 20%.
• via β2-adrenergic blockade, NSBBs cause splanchnic vasoconstriction due to
unopposed adrenergic tone, with a subsequent additional decrease in portal-collateral
blood flow of about 15%, for a total 35% reduction in portal venous inflow. This is the
mechanism by which NSBBs decrease the portal pressure by approximately 15%.

36. HOW BB WORKS ?
(Via an unopposed adrenergic tone, NSBBs cause a mild increase in peripheral and hepatic
resistance, which explains why patients under NSBB do not develop arterial hypotension and
why the effect on portal pressure is relatively mild. )
• Carvedilol is a NSBB that has an intrinsic anti-α1 adrenergic effect, which causes
intrahepatic vasodilatation and further decreases portal pressure.

38. ALGORITHM FOR MX OF AVH IN PTS WITH LC
*Any of the following: varix spurting blood, varices with overlying clot or with white nipple sign, varices and no other lesion that would explain hemorrhage.
**A short-term course (10 days) of PPI may reduce the size of post-banding ulcers.
Zanetto A, et al. Management of acute variceal hemorrhage. F1000Research 2019, 8(F1000 Faculty Rev):966
38/56

39. ALGORITHM FOR MX OF AVH IN PTS WITH LC
***Excluding pts >75 years old or who have HCC outside Milan criteria, creat of at least 3 mg/dL, previous combination pharmacological plus endoscopic treatment to prevent re-
bleeding, bleeding from isolated gastric or ectopic varices, recurrent HE, pulmonary HTN, or heart failure or a combination of these.
†Patient should not be discharged on prophylactic antibiotic (consider discontinuing at same time as vasoactive drugs).
Zanetto A, et al. Management of acute variceal hemorrhage. F1000Research 2019, 8(F1000 Faculty Rev):966
39

40. ROLE OF TIPS
Guidelines[1,2,3] recommend TIPS placement in the following pts at the time of acute
VH:
1. Rescue TIPS in pts with persistent bleeding or early re-bleeding despite treatment
with vasoconstrictors plus EVL.
2. Early (within 24 to 72 hours) pre-emptive TIPS can be considered in high-risk pts
(Child C with score < 14) without CI to TIPS.
High risk pt: HVPG≥ 20 mmHg or those with active bleeding at endoscopy[5] or MELD>18 [4]
1. de Franchis R, Baveno VI Faculty: Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;
63(3): 743–52.
2. European Association for the Study of the Liver: EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018; 69(2): 406–60.
3. Garcia-Tsao G, Abraldes JG, Berzigotti A, et al.: Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver
diseases. Hepatology. 2017; 65(1): 310–35.
4. Lv Y, Zuo L, Zhu X, et al.: Identifying optimal candidates for early TIPS among patients with cirrhosis and acute variceal bleeding: a multicentre observational study. Gut. 2019; 68(7): 1297–1310.
5. Monescillo A, Martínez-Lagares F, Ruiz-del-Arbol L, et al. Influence of portal hypertension and its early decompression by TIPS placement on the outcome of variceal bleeding. Hepatology 2004; 40:793.
40

41. TRANSJUGULAR INTRAHEPATIC PORTO-
SYSTEMIC SHUNT
• TIPS involve creation of a low-resistance channel
between the hepatic vein and the intrahepatic
portion of the portal vein (usually the right
branch) using angiographic techniques.
• The tract is kept patent by deployment of an
expandable metal stent across it, thereby
allowing blood to return to the systemic
circulation.
• A TIPS is placed to reduce portal pressure in pts
with complications related to PHTN.[1,2]
1. Colombato L. The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension.
J Clin Gastroenterol. 2007 Nov-Dec. 41 Suppl 3:S344-51.
2. Gaba RC, Omene BO, Podczerwinski ES, Knuttinen MG, Cotler SJ, Kallwitz ER, et al. TIPS for Treatment of Variceal
Hemorrhage: Clinical Outcomes in 128 Patients at a Single Institution over a 12-Year Period. J Vasc Interv Radiol. 2011
Dec 16. Pic src: Sankar K, edt al. Transjugular Intrahepatic Portosystemic Shunts. JAMA. 2017;317(8):880.
41

42. TIPSS; COMPLICATIONS
• EARLY EVENTS: Bacteriemia: Bacteriemia after TIPS (defined by fever >38.5°C,
or leukocytosis >15.000 / ul and positive blood cultures) .
• LATE EVENTS: Endotipsitis: Defined by the presence of sustained bacteriemia
a/with the evidence of thrombus or vegetations inside the TIPS. This clinical
condition is rare (1%).
• Hepatic encephalopathy: HE is one of the major complications of TIPS. The
incidence of HE post-TIPS varies around 40 %. Besides conventional management
of HE, Stent lumen reduction or occlusion is effective in case of persistent overt
post-TIPS HE.
42
Although TIPSS is associated with less rebleeding than endoscopic therapy, survival is not improved.
TIPS may be futile in pts with Child-Pugh ≥14 cirrhosis, or with a MELD score >30 and lactate >12 mmol/L, unless
liver transplantation is envisioned in the short-term. The decision to perform TIPS in such patients should be taken on
a case-by-case basis.

43. ALGORITHM FOR MX OF AVH IN PTS WITH LC
*Any of the following: varix spurting blood, varices with overlying clot or with white nipple sign, varices and no other lesion that would explain hemorrhage.
**A short-term course (10 days) of PPI may reduce the size of post-banding ulcers.
Zanetto A, et al. Management of acute variceal hemorrhage. F1000Research 2019, 8(F1000 Faculty Rev):966
43/56

44. BALLOON TAMPONADE
• Use of standard measures fails to control
bleeding in approx 10-20% of pts with AVH.
• In this setting, use of balloon tamponade
may be necessary as a temporary stabilizing
therapy until a more definitive procedure,
such as endoscopic variceal ligation or TIPS,
can be performed.
• The use of BT is a/with serious potential
A/E, and it should not be used for longer
than 24 hours.

45. youtube: Linton, Blakemore, & Minnesota Tubes Overview

46. SELF-EXPANDABLE METAL ESOPHAGEAL STENTS
• Self-expandable metal esophageal stents
were shown in a small multicenter,
randomized, controlled trial to be a
reasonable alternative to achieve
hemostasis in those who did not respond
to medical and endoscopic therapy, and
these can remain in place up to seven days,
while awaiting more definitive therapy.
Youtube: Danis stent animation

47. OTHER
• Portosystemic shunt surgery: Surgery prevents recurrent bleeding but carries a high
mortality and often leads to encephalopathy.
• In practice, portosystemic shunts are now reserved for when other treatments have
not been successful and are offered only to patients with good liver function.
• Oesophageal transection: Rarely, surgical transection of the varices may be
performed as a last resort when bleeding cannot be controlled by other means but
operative mortality is high.

48. PROPHYLAXIS OF VARICEAL HEMORRHAGE (VH)
H/o VH
VH prevention measures
for pts with a known
H/o VH
Secondary Prophylaxis
• Beta-blockers are used as a secondary measure to
prevent recurrent variceal bleeding.
• Following successful endoscopic therapy, pts should be
entered into an EVL programme with repeated sessions
of therapy at 12–24-week intervals until the varices are
obliterated.
• In selected individuals, TIPSS may also be considered in
this setting.

49. Next Class
Ascites
1
2
3
Refractory Ascites
4 Hepatorenal Syndrome
Spontaneous bacterial Peritonitis